Liver Diseases

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1. Role of free radicals in liver diseases and hepatic fibrosis.
An increased production of free radicals in the liver has been implicated in a variety of liver
diseases. Free radicals can damage cellular macromolecules and, therefore, may participate in
hepatocellular injury when produced in excess. Strong evidence exists for hepatic free radical
production in animal models of iron and copper overload, ethanol consumption, and ischemiareperfusion. Although less is known about the situation in humans with liver diseases, the
available evidence is consistent with the findings in animal experiments. Treatments that reduce
free radical production and/or levels have protective effects in hepatic ischemia-reperfusion.
Free radical-initiated lipid peroxidation may play a role in hepatic fibrogenesis, perhaps through
an effect of aldehydic peroxidation products on Kupffer cells and lipocytes. This hypothesis is
supported by the observation that dietary supplementation with vitamin E has a protective effect
on carbon tetrachloride-induced hepatic fibrosis. While cellular damage in human liver
diseases is probably multifactorial, free radicals may play important roles in initiating and/or
perpetuating this damage.
2.Immunogenetics of chronic liver diseases.
The genetic background of autoimmune diseases becomes more and more evident.
Immunogenetics comprises the analysis of genes and their products located at the region 6p21 on
the short arm ofchromosome 6, which is also known as the major histocompatibility complex
(MHC). MHC class I and II genes are highly polymorphic. The complement genes
C2, C4A, C4B, and BF, which are also polymorphic, became known as MHC class III genes.
In autoimmune hepatitis type 1, there is a dual association for white persons with either HLAA1-B8-DR3 or HLA-DR4. In patients from Japan,autoimmune hepatitis type 1 is predominantly
associated with HLA-DR4. This dual association is confirmed at the DNA level. Whereas only
limited data are available for autoimmune hepatitis type 2, the association of primary biliary
cirrhosis with HLA-DR8 is based on several studies. Primary sclerosing cholangitis is associated
with HLA-B8-DR3 and -DR52a. This association was confirmed at the DNA level because of a
significant increase of the DRB3*0101 allele. For DRB3*0101-negative individuals, a second
association with DRB5*0101 (= DR2) was described. Further analysis of the hypervariable
region of the HLA class II molecule indicates that lysine at position 71 is crucial forautoimmune
hepatitis type 1 in white persons, whereas position 13 is important for people from Japan. In
contrast, leucine at position 35 is important for patients with primary biliary cirrhosis, whereas
leucine at position 38 is an important risk factor for primary sclerosing cholangitis. The MHC
class III allele C4A-QO is significantly increased in autoimmune hepatitis type 1 and 2 and
in primary biliary cirrhosis. Advances in immunogenetics will certainly increase our knowledge
of the etiology andpathogenesis of immune-mediated liver diseases, which hopefully will lead to
more specific therapeutic interventions.
3.Relation between autoimmune liver diseases and viral hepatitis: clinical and serological
characteristics in 859 patients.
An etiopathological link between hepatitis virus infection and autoimmune liver disease, in
particularautoimmune hepatitis has been suggested. In some patients features of both viral
and autoimmune disease are present. We have studied 352 patients with autoimmune liver
disease and 507 patients with viral hepatitis for diagnostic characteristics as well as for evidence
of an etiological connection. 38 of the 201 patients with hepatitis C (19%) and 42 of the 306
patients with hepatitis B (14%) had significant titres of autoantibodies (ANA, SMA or
LKM). SLA autoantibodies were found exclusively in patients with autoimmune liver disease.
LKM auto-antibody was found in only one of the 201 HCVpatients. Evidence of past or
present hepatitis B virus and past hepatitis A virus infection was most common in the hepatitis C
virus patients and least common in autoimmune hepatitis. 28 of the 352 patients
with autoimmune liver diseases tested positive in the second generation anti-HCV ELISA, but
only five patients (two with autoimmune hepatitis, one with primary sclerosing cholangitis and
two withprimary biliary cirrhosis) were positive in confirmatory anti-HCV assays, and only in
these could HCV-RNA be isolated. Autoimmune hepatitis patients had significantly higher
transaminase, GLDH and IgG levels. HLA-B8, HLA-DR3 and HLA-DR4 were significantly
more common in autoimmune hepatitis. Distinction between autoimmune liver disease and
viral hepatitis C could be made reliably on clinical and laboratory grounds. Our data show that a
link between hepatitis A, B, or C virus infection andautoimmune liver diseases is highly
unlikely.(ABSTRACT TRUNCATED AT 250 WORDS).
4.Fatty liver hepatitis and cirrhosis in obese patients
Liver function and liver biopsy findings were studied in a selected group of 29 overweight
patients. Fatty liver, fatty hepatitis, fatty fibrosis and fatty cirrhosis were seen with equal
frequency. Diabetes was also present with an equal incidence in each of these four pathologic
groups. Lipoprotein abnormalities, particularly type IV hyperlipoproteinemia, were found mostly
in the two groups with the lesions with less fibrosis (fatty liver and fatty hepatitis). The
pathologic picture resembled that of alcohol and postjejunoileal bypass-induced liver diseases
suggesting a common denominator in these three conditions.
5. Epidemiology of alcoholic liver disease.
Although there exists a relationship between alcohol consumption and alcoholic liver disease at
both the aggregate and individual levels, it is also well established that less than one-third of
alcoholics or heavy drinkers develop serious alcohol-related liver damage. A number of factors
have been proposed to account for this susceptibility. Evidence supporting the direct doseresponse relationship and the role of genetic and environmental factors in influencing
vulnerability are reviewed. To date, no consistent evidence attests to the significance of any one
factor in the susceptibility to developingalcoholic liver disease.
6.Oxidative damage and fibrogenesis
Various chronic disease processes are characterized by progressive accumulation of connective
tissue under-going fibrotic degeneration. Evidence of oxidative reactions is often associated with
fibrogenesis occurring in liver, lung, arteries, and nervous system. Moreover, an increasing bulk
of experimental and clinical data supports a contributory role of oxidative stress in
the pathogenesis of this kind of disease. Indeed, many etiological agents of fibrogenesis
stimulate free radical reactions either directly or through inflammatory stimuli. Free radicals, as
well as products of their reaction with biomolecules, appear to modulate the activity of the two
cellular types mainly involved in the process, namely phagocytes and extracellular matrixproducing cells. Lipid peroxidation and certain lipidperoxidation products induce genetic
overexpression of fibrogenic cytokines, the key molecules in the pathomechanisms of fibrosis, as
well as increased transcription and synthesis of collagen. Both these events can be
downregulated, at least in experimental models, by the use of antioxidants. The effect of
oxidative stress on cytokine gene expression appears to be an important mechanism by which it
promotes connective tissue deposition.
7.Pathogenesis of liver fibrosis: role of oxidative stress
In the liver, the progressive accumulation of connective tissue, a complex and dynamic process
termed fibrosis, represents a very frequent event following a repeated or chronic insult of
sufficient intensity to trigger a "wound healing"-like reaction. The fibrotic process recognises the
involvement of various cells and different factors in bringing about an excessive fibrogenesis
with disruption of intercellular contacts and interactions and of extracellular matrix composition.
However, Kupffer cells, together with recruited mononuclear cells, and hepatic stellate cells are
by far the key-players in liver fibrosis. Their cross-talk is triggered and favoured by a series of
chemical mediators, with a prominent role played by the transforming growth factor beta. Both
expression and synthesis of this inflammatory and pro-fibrogenic cytokine are mainly modulated
through redox-sensitive reactions. Further, involvement of reactive oxygen species
and lipid peroxidation products can be clearly demonstrated in other fundamental events of
hepatic fibrogenesis, like activation and effects of stellate cells, expression of metalloproteinases
and of their specific inhibitors. The important outcome of such findings as regards
the pathogenesis of liver fibrosis derives from the observation of a consistent and marked
oxidative stress condition in many if not all chronic disease processes affecting hepatic tissue.
Hence, reactive oxidant species likely contribute to both onset and progression of fibrosis as
induced by alcohol, viruses, iron or copper overload, cholestasis, hepatic blood congestion.
8.The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats
PURPOSE: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an
antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still
few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to
clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in
cholestatic rats.
MATERIALS AND METHODS: We performed bile duct ligation on 7-week-old male
cholestatic Wistar rats and assigned them to one of three groups according to the method of
treatment: (1) the SHAM group, (2) the NT-group (non-treatment group), and (3) the T-group
(treatment-group). Rats in the T-group were orally administered ICKT (TJ-135) at a dose of 1
g/kg/day and were killed on the 17th postoperative day. We subsequently investigated the levels
of fibrosis and various clinical markers through measurement of the following: serum levels
of AST and ALT; tissue transforming growth factor-beta 1 (TGF-beta1); tissue
inhibitor metalloprotease-1 mRNA (TIMP-1 mRNA) through real-timePCR analysis; and Azan
staining and immunohistochemical staining of alfa-smooth muscle actin (alfa-SMA) to evaluate
the degree of fibrosis.
RESULTS: The levels of serum AST, serum ALT, and TGF-bata1 in the T-Group were
significantly lower than those in the NT-Group. In addition, staining of Azan and alfa-SMA in
the T-Group was significantly lower than those in the NT-Group.
CONCLUSION: ICKT may help reduce hepatic fibrosis and injury by controlling stellate cell
activation.
9.Effect of weight reduction on hepatic abnormalities in overweight patients
(PMID:2210247)
Palmer M, Schaffner F
Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine of the City
University of New York, New York.
Gastroenterology [1990, 99(5):1408-1413]
Abstract
The effects of weight reduction on hepatic test results and physical findings related to the liver
were retrospectively evaluated in 39 overweight patients screened to exclude other factors
affecting the liver. An additional 11 overweight patients with primary liver disease were
retrospectively evaluated to compare the effect of weight reduction in patients with liver
disease with its effect in those without primary liver disease. This study showed that in
overweight adults without primary liver disease, a weight reduction of greater than or equal to
10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some
stigmata of liver disease. In similarly studied overweight patients with primary liver disease,
some findings improved, but the changes did not correlate with a greater than or equal to 10%
weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme
abnormality in this population. For every 1% reduction in body weight,alanine aminotransferase
activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and
biochemical parameters, weight reduction should be tried for overweight patients with abnormal
hepatic test results in the absence of obvious primary liver disease as judged by clinical and
biochemical parameters before extensive and expensive studies are undertaken.
10.Criteria of drug-induced liver disorders. Report of an international consensus meeting.
(PMID:2254635)
Type: Consensus Development Conference, Journal Article, Review
DOI: 10.1016/0168-8278(90)90124-A
Abstract
International reporting of adverse drug reactions by pharmaceutical manufacturers to national

drug regulatory authorities requires internationally accepted standard definitions of reactions
and criteria for assessment of causality. The Council for International Organizations of Medical
Sciences (CIOMS) undertook a pilot project to prepare such definitions and criteria, and
proposed to use as its model a series of expert consensus meetings organized in France by the
pharmaceutical company, Roussel Uclaf, with the participation of the official French network of
pharmacovigilance. Under CIOMS auspices, an international meeting was organized to test the
feasibility of adapting for international use the outcome of the French consensus meetings on
drug-induced liver disorders. The meeting resulted in a series of proposed standard designations
of drug-induced liver disorders and criteria of causality assessment.
11.Vulnerability to psychologic distress and depression in patients with end-stage liver disease
due to hepatitis C virus.
(PMID:9361931) Type: Journal Article, Comparative Study
Abstract
Psychosocial sequelae and quality of life impairment in patients with end-stage liver disease due
tohepatitis C virus (HCV) are not known. Quality of life, psychological distress (Profile of
Mood State scale), depression (Beck Depression Inventory), and coping (Ways of Coping scale)
were prospectively assessed in 82 liver transplant candidates; comparisons were made between
patients with HCV hepatitis versus patients with other liver diseases. Patients with HCV were
significantly younger than all other patients (p = 0.002). Total mood disturbance (p = 0.038),
tension and anxiety (0.047), confusion and bewilderment (p = 0.035) and depression and
dejection (p = 0.035), as assessed by Profile of Mood States Scale were significantly higher in
patients with HCV than other patients. Patients with HCV were significantly more depressed as
assessed by Beck Inventory scores (p = 0.014). Karnofsky performance scores, Child-Pugh
score, and liver function tests were not significantly different for patients with HCV vs. all other
patients. However, somatic manifestations of the illness (e.g. pain) were greater in patients
with HCV and may have contributed towards greaterdepression in these patients. Our findings
warrant replication in other studies, since depression is a modifiable and treatable disorder.
12.Lethal hepatocellular necrosis associated with herbal polypharmacy in a patient with chronic
hepatitis B infection.
(PMID:24915453)
Gilbert JD, Musgrave IF, Hoban C, Byard RW
Forensic Science SA, Adelaide, SA 5000, Australia.
Forensic Science International [2014, 241:138-140]
Type: Journal Article
DOI: 10.1016/j.forsciint.2014.05.021
Abstract
Following a short treatment for irritable bowel with the following herbs: Astragalus
propinquus,Codonopsis pilosula, Paeonia sp., Atractylodes macrocephala, Pueraria sp., Poria
cocos, Dioscorea opposita, Patriniae, Psoralea corylifolia, Alpinia katsumadai, Glycyrrhiza
uralensis and Dolomiaeasouliei sp. a 43-year-old woman developed acute severe liver failure
requiring liver transplantation. Histopathological examination of the liver showed
massive hepatic necrosis in keeping with drug/chemical toxicity. Surgery was followed by
multiorgan failure and death. While numerous studies have evaluated the effect of
polypharmacy, the study of multiple concurrent herb use is only just emerging, despite the
popularity of herbal medicine use in the western world. As this case demonstrates that fulminant
hepatic failure and death may be caused by the concomitant use of a number of herbal products,
the possibility of untoward effects from herbal polypharmacy must be increasingly considered in
the evaluation of medicolegal cases.
13. Contamination and adulteration of herbal medicinal products (HMPs): an overview of
systematic reviews.
Posadzki P, Watson L, Ernst E
Complementary Medicine, Peninsula Medical School, University of Exeter, Veysey Building,
Salmon Pool Lane, Exeter EX2 4SG, UK. paul.posadzki@pcmd.ac.uk
European Journal of Clinical Pharmacology [2013, 69(3):295-307]
Type: Journal Article, Review
DOI: 10.1007/s00228-012-1353-z
PURPOSE: The aim of this overview of systematic reviews is to summarise and critically
evaluate the evidence from systematic reviews of the adulteration and contamination of herbal
medicinal products (HMPs).
METHODS: Five electronic databases were searched to identify all relevant systematic reviews.
RESULTS: Twenty-six systematic reviews met our inclusion criteria. The most
commonly HMPs were adulterated or contaminated with dust, pollens, insects, rodents,
parasites, microbes, fungi, mould, toxins, pesticides, toxic heavy metals and/or prescription
drugs. The most severe adverse effects caused by these adulterations
were agranulocytosis, meningitis, multi-organ failure, perinatal stroke,arsenic, lead or mercury
poisoning, malignancies or carcinomas, hepatic encephalopathy, hepatorenal syndrome,
nephrotoxicity, rhabdomyolysis, metabolic acidosis, renal or liver failure, cerebral edema,coma,
intracerebral haemorrhage, and death. Adulteration and contamination of HMPs were most
commonly noted for traditional Indian and Chinese remedies, respectively.
CONCLUSIONS: Collectively these data suggest that there are reasons for concerns with
regards to the quality of HMPs. Adulteration and contamination of HMPs can cause serious
adverse effects. More stringent quality control and its enforcement seem to be necessary to avoid
health risks.
14. Forensic problems with the composition and content of herbal medicines
Blacksell L, Byard RW, Musgrave IF
School of Health Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005,
Australia.
Journal of Forensic and Legal Medicine [2014, 23:19-21]
DOI: 10.1016/j.jflm.2014.01.008
Abstract
A survey of herbal medicines available for internet and over-the-counter purchase in South
Australia, Australia, was conducted looking specifically at those used for 'arthritis', 'cold and
flu', 'gastrointestinal', 'stress' and 'premenstrual syndrome'. 121 products consisted of 29 in the
'arthritis' category, 33 in 'cold and flu', 19 in 'gastrointestinal' 30 in 'stress' and 10 in
'premenstrual syndrome'. Twenty two (18%) of 121 products were not registered with the
Australian Register of Therapeutic Goods (ARTG), despite this being a legal requirement for
their sale. Of the registered products 59 (60%) of 99 had differing ingredient concentrations on
the website compared to their ARTG listing. Only three of the 15 purchased products had
ingredient concentrations which were consistent between the website, ARTG listing and product
packaging. These findings demonstrate that it may not be possible to determine what herbal
substance an individual has been exposed to prior to death and in what concentration, based on
packaging from medications seized at the scene, or from examination of website data and the
ARTG listing. These discrepancies may increase the problems that exist in attempting to
determine what role herbal medicines may play in the mechanism of death in certain forensic
cases.
15.Detecting organic toxins in possible fatal poisonings--a diagnostic problem.
(PMID:15274954)
Byard RW, James RA, Felgate P
Forensic Science Centre, Adelaide, South Australia, Australia. byard.roger@saugov.sa.gov.au
Journal of Clinical Forensic Medicine [2002, 9(2):85-88]
DOI: 10.1054/jcfm.2002.0559
Abstract
Highlight Terms
Species(1)
Chemicals(1)
Two fatal cases are reported where there was strong circumstantial evidence of plant toxin
ingestion. In only one case however was a low urine level of hyoscine detected (in keeping with
a history ofDatura sp. consumption). Fatal cases of plant toxin ingestion may be a problem for
the laboratory given the wide range and rarity of certain plant poisons, and the limitation of
standard screening. Identification of plant materials at the scene of suspected poisoning may be
crucial in directing toxicological investigations.
16.Effect of weight reduction on hepatic abnormalities in overweight patients.
(PMID:2210247)
Palmer M, Schaffner F
Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine of the City
University of New York, New York.
Gastroenterology [1990, 99(5):1408-1413]
Abstract
Highlight Terms
Gene Ontology(1)
Diseases(1)
The effects of weight reduction on hepatic test results and physical findings related to the liver
were retrospectively evaluated in 39 overweight patients screened to exclude other factors
affecting the liver. An additional 11 overweight patients with primary liver disease were
retrospectively evaluated to compare the effect of weight reduction in patients with liver
disease with its effect in those without primary liver disease. This study showed that in
overweight adults without primary liver disease, a weight reduction of greater than or equal to
10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some
stigmata of liver disease. In similarly studied overweight patients with primary liver disease,
some findings improved, but the changes did not correlate with a greater than or equal to 10%
weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme
abnormality in this population. For every 1% reduction in body weight,alanine aminotransferase
activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and
biochemical parameters, weight reduction should be tried for overweight patients with abnormal
hepatic test results in the absence of obvious primary liver disease as judged by clinical and
biochemical parameters before extensive and expensive studies are undertaken.
17.The beneficial effects of Momordica charantia (bitter gourd) on wound healing of rabbit skin.
(PMID:22812507)
Pikin A, Altunkaynak BZ, Tmentemur G, Kaplan S, Yazc OB, Hkelek M
Departments of Orthopedic and Trauma Surgery, Medical School of Ondokuz Mays University ,
Samsun , Turkey.
The Journal of Dermatological Treatment [2014, 25(4):350-357]
DOI: 10.3109/09546634.2012.713459
Abstract
Highlight Terms
Gene Ontology(1)
Species(4)
Chemicals(2)
Momordica charantia (MC; bitter gourd) is a traditional herbal commonly used for
its antidiabetic,antioxidant, contraceptive and antibacterial properties. In the current study, the
authors aim to observe the topical effect of MC cream on the wound-healing process in rabbits.
Moreover, they compare the healing potential with conventional creams used therapeutically.
Towards this aim, 28 New Zealand rabbits were divided into four groups and excision wounds
(7 cm) were made on their backs. Open wound dressing was carried out daily for 28 days
among the experimental groups with the application of dekspanthenol (Bepanthen; BP group,
n = 7), nitrofurazon (Furacin; FR group, n = 7) and olive oil extract of MC (MC group, n = 7).
No application was made to the control group. At the end of day 28, areas of the skin with initial
wound area were en bloc dissected and prepared for histopathological and stereological analysis.
Inflammatory cells were abundant in the control group and cream application led to a decrease
in the number of these cells, especially in the MC group. The highest number of fibroblasts was
detected in the MC group. Furthermore, the MC group displayed the highest fractions of
epidermis to papillary dermis, fibroblasts to reticular dermis and collagen fibres to reticular
dermis. The MC group also presented a high density of blood vessels, moderate density
of collagenfibres and mature fibroblasts. The BP group showed better epithelialisation compared
with the FR group, but the latter provided more effective reorganisation of the dermis. Different
cream supplements caused healthy and fast wound healing according to untreated controls and
the results show that administration of the MC extract improves and accelerates the process of
wound healing in rabbits in comparison with the BP and FR extracts.
18.Implications from a pharmacogenomic analysis: Nerium oleander leaf distillate supplemented
diet regulates cholesterol metabolism in rats
Demirel Kars M, Odaba BA, Kars G, Uney K, Bac Y, Ba AL
Sarayn Vocational High School, Seluk University , Konya , Turkey .
Pharmaceutical Biology [2014, 52(8):988-993]
DOI: 10.3109/13880209.2013.874535
Abstract
Highlight Terms
Gene Ontology(1)
Species(4)
Abstract Context: Despite the usage of Nerium oleander L. (Apocynaceae) for anticancer studies
and traditional remediation, the regulatory effect of N. oleander leaf distillate on cholesterol
metabolism is not disclosed sufficiently.
Objective: Cholesterol is an important biological molecule and the synthesis rate is regulated by
the amount of cholesterol uptake from the diet. The aim of this study was to investigate the
regulation ofcholesterol metabolism in response to a high-fat diet (HFD) and the effects of N.
oleander leaf distillate-supplemented diet (NOHFD) in rats.
Materials and methods: Microarray technology was used to clarify the regulation of cholesterol
mechanism in HFD and NOHFD-fed rats (375g/0.5mL distilled water applied by gavage). The
treatment period was 90 days. Rat liver tissues were used for microarray analysis using the
Affymetrix GeneChip Rat Genome platform. Results of groups were statistically analyzed with
the Partek 6.6 bioinformatic program.
Results: The HFD group exhibited alterations in the expression levels of about 1945 genes with
respect to the normal diet (ND) group. The results showed that expression levels of 47 genes
were altered related to cholesterol metabolism in HFD and NOHFD groups. The expression
levels of seven genes in the NOHFD group were significantly closer to those in the ND group
than those of the HFD group.
Discussion and conclusion: To conclude, findings suggest that N. oleander leaf distillatesupplemented food has considerable beneficial effects on cholesterol metabolism-related gene
expression levels.
19.Evaluation of hepatoprotective activity of vasicinone in mice
Sarkar C, Bose S, Banerjee S
Indian Journal of Experimental Biology [2014, 52(7):705-711]
Type: Evaluation Studies, Journal Article
Abstract
Highlight Terms
Diseases(1)
Genes/Proteins(2)
Species(5)
Chemicals(3)
Justicia adhatoda (vasaka) leaves have long been used in Indian Ayurvedic system of medicine
asantitussive. Its crude extract has been previously reported to have hepatoprotective activity.
Vasicinone was isolated from leaves of J. adhatoda, column purified and characterized using,
TLC UV, FT-IR and 1H NMR. The isolated vasicinone was evaluated for hepatoprotective
activity using (CCl4)-induced acute hepatotoxicity model in mice. CCl4 treatments lead to
significant increase in SGOT, SGPT, ALP levels. Pre-treatment with vasicinone and silymarin
(25 mg/kg/day for 7 days) significantly decreased these enzyme levels. Histopathology of the
livers from vasicinone and silymarin pre-treated animals showed normal hepatic cords and
absence of necrotic changes suggesting pronounced recovery from CCl4 induced liver damage.
Both vasicinone and silymarin significantly decrease the CCl4 mediated increase
in pentobarbital indiced sleeping time in experimental animals, thus indicating recovery of liver
function. Based on the above results it can be concluded that vasicinone may act as
hepatoprotective in mice and warrants further investigation onhuman volunteers

20.Sedum sarmentosum Bunge extract exerts renal anti-fibrotic effects in vivo and in vitro.
(PMID:24747135)
Bai Y, Lu H, Zhang G, Wu C, Lin C, Liang Y, Chen B
Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical
University, Wenzhou 325000, China.
Life Sciences [2014, 105(1-2):22-30]
Type: Journal Article, Research Support, Non-U.S. Gov't
DOI: 10.1016/j.lfs.2014.04.013
Abstrac
t
Highlight Terms
Gene Ontology(2)
Diseases(6)
Genes/Proteins(5)
Species(3)
Chemicals(1)
AIMS: Sedum sarmentosum Bunge, a traditional Chinese herbal medicine, has a wide range of
clinical effects, including anti-oxidation, anti-inflammation, and anti-cancer properties. In this
study, we determined whether S. sarmentosum Bunge Extract (SSBE) has anti-fibrotic effects on
renal tissues.MAIN METHODS: We investigated the effects of SSBE on aristolochic acid (AA)induced injury to renal tubular epithelial cells (RTECs) in vitro and unilateral ureteral
obstruction (UUO)-induced renal fibrosis in vivo by evaluating epithelial-to-mesenchymal
transition (EMT) and the accumulation ofextracellular matrix (ECM) components. Furthermore,
we examined the expression levels of TGF-1 and its receptor.
KEY FINDINGS: In cultured RTECs (NRK-52E), AA promoted
renal EMT and ECM accumulation by up-regulating the expression of mesenchymal markers
and ECM components and by down-regulating the expression of epithelial markers. In addition,
AA induced an imbalance between MMP-2 and TIMP-2 and enhanced expression of TGF-1
and its receptor. SSBE treatment significantly inhibited AA-induced TGF-1 expression and
prevented the induction of EMT and deposition of ECM. In the UUOrats, tubular injury
and interstitial fibrosis were obviously increased. SSBE administration protected renal function,
as indicated by reduced serum creatinine levels, and alleviated renal interstitial fibrosis. These
anti-fibrotic effects were associated with a reduction in TGF-1 expression and inhibition
ofEMT and ECM accumulation.
SIGNIFICANCE: These findings suggest that SSBE may have therapeutic potential for
fibrotic kidney diseases
21. Protective effect of total alkaloids on lipopolysaccharide-induced acute lung injury.
(PMID:24594217)
Niu X, Hu H, Li W, Li Y, Huang H, Mu Q, Yao H, Li H

School of Pharmacy, Xi'an Jiaotong University, Xi'an, P.R China.
The Journal of Surgical Research [2014, 189(1):126-134]
DOI: 10.1016/j.jss.2014.01.065
Abstrac
t
Highlight Terms
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Diseases(1)
Genes/Proteins(3)
Species(2)
Chemicals(4)
BACKGROUND: Corydalis denticulato-bracteata Fedde is used as a traditional herbal medicine

for the treatment of pneumonia. However, there is no scientific evidence, which validate the use
of totalalkaloids of denticulato-bracteata Fedde in the literature. MATERIALS AND
METHODS: Male Kunming mice were randomly divided into seven groups (n = 12, each):
control group, total alkaloidsalone (200 mg/kg, intragastric gavage), LPS group, and three
different doses (50, 100, and 200 mg/kg, intragastric gavage) for total alkaloids-treated
groups, Dexamethasone (5 mg/kg, intraperitoneally) group. Corresponding drugs or vehicles
were given 24 and 1 h before lipopolysaccharide (LPS) administration (5 mg/kg,
intraperitoneally). The severity of pulmonary injury was evaluated 6 h after LPS challenge.
RESULTS: As revealed by survival study, pretreatment with total alkaloids significantly reduced
LPS-induced death. We also found that total alkaloids pretreatment markedly decreased the lung
wet-to-dry weight ratios and significantly attenuated histopathologic changes. Moreover,
total alkaloids decreased the production of the tumor necrosis factor and nitric oxide in the
serum and bronchoalveolar lavage fluid. Total alkaloids pretreatment also reduced LPS-induced
inducible nitric oxide synthase and p65nuclear factor kappa B protein expression in the lung.
CONCLUSIONS: This study indicates that total alkaloids may have a protective effect against
LPS-induced acute lung injury. This protective effect of total alkaloids seems to result from
inhibition of nuclear factor kappa B activation, which causes the reduction of inflammatory
markers such as tumor necrosis factor and inducible nitric oxide synthase.
22. Antihyperglycemic effects of three extracts from Momordica charantia.
(PMID:12902059)
Virdi J, Sivakami S, Shahani S, Suthar AC, Banavalikar MM, Biyani MK
Department of Life Science, University of Mumbai, Kalina, Santacruz East, 400 098 Mumbai,
India.
Journal of Ethnopharmacology [2003, 88(1):107-111]
Type: Journal Article, Comparative Study
DOI: 10.1016/S0378-8741(03)00184-3
Abstract
Highlight Terms
Diseases(2)
Genes/Proteins(1)
Species(4)
Chemicals(3)
Momordica charantia (L.) (Cucurbitaceae) commonly known as bitter gourd or karela is a

medicinal plant, used in Ayurveda for treating various diseases, one of which is diabetes
mellitus. In this study, various extract powders of the fresh and dried whole fruits were prepared
and their blood glucoselowering effect compared by administrating them orally to diabetic rats.
The aqueous extract powder of fresh unripe whole fruits at a dose of 20mg/kg body weight was
found to reduce fasting blood glucoseby 48%, an effect comparable to that of glibenclamide, a
known synthetic drug. This extract was tested for nephrotoxicity, hepatotoxicity and biochemical
parameters such as SGOT, SGPT and lipidprofile. The extract did not show any signs of
nephrotoxicity and hepatotoxicity as judged by histological and biochemical parameters. Thus
the aqueous extract powder of Momordica charantia, an edible vegetable, appears to be a safe
alternative to reducing blood glucose.
23.Anti-ulcerogenic effect of Momordica charantia L. fruits on various ulcer models in rats.
(PMID:10904148)
Grbz I, Akyz C, Yeilada E, Sener B
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Hipodrom 06330,
Ankara, Turkey.
Journal of Ethnopharmacology [2000, 71(1-2):77-82]
DOI: 10.1016/S0378-8741(99)00178-6
Abstract
Highlight Terms
Diseases(1)
Species(3)
Chemicals(4)
The mature fruits of Momordica charantia L. (Cucurbitaceae) are used externally for the rapid
healing of wounds and internally for the treatment of peptic ulcers in Turkish folk medicine. For
the evaluation of the latter activity, ethanol-induced ulcerogenesis model in rats was employed.
The olive oil extract of the material as well as dried-powdered fruits in filtered honey showed
significant and dose-dependent anti-ulcerogenic activity against this model. A potent and dosedependent inhibitory activity was also observed by the administration of ethanol extract of the
fruits. For the bioassay-guided fractionation, the material was first extracted with hexane and
then by ethanol and both extracts were found active against the same ulcer model.
Furthermore, ethanol extract of the fruits showed significant activity against HCl-EtOH induced
ulcerogenesis in indomethacin-pretreated rats and diethyldithiocarbamate-induced ulcer models
24.
Review of complementary and alternative medical treatment of arrhythmias.
(PMID:24528618)
Brenyo A, Aktas MK
Department of Medicine, Greenville Health System, Greenville, South Carolina. Electronic
address: Andrew_Brenyo@urmc.rochester.edu.
The American Journal of Cardiology [2014, 113(5):897-903]
DOI: 10.1016/j.amjcard.2013.11.044
Abstract
Highlight Terms
Genes/Proteins(1)
Complementary and alternative medical (CAM) therapies are commonly used by patients for the
treatment of medical conditions spanning the full spectrum of severity and chronicity. The use of
alternative remedies, both herbal and others, for conditions lacking effective medical treatment,
is on the increase. Included within this categorization, arrhythmic disease-absent effective
catheter-based therapy or with medical therapy limited by the toxicities of contemporary
antiarrhythmic agents is frequently managed by patients with CAM therapies without their
practitioner's knowledge and in the face of potential herb-drug toxicities. This study reviews 9
CAM therapies: 7 individual herbal therapies along with acupuncture and yoga that have been
studied and reported as having an antiarrhythmic effect. The primary focuses are the proposed
antiarrhythmic mechanism of each CAM agent along with interactions between
the CAM therapies and commonly prescribed medical therapy for arrhythmia patients. We stress
persistent vigilance on the part of the provider in discussing the use of herbal or
other CAM agents within the arrhythmia population.
25. The anti-inflammatory effect of diclofenac is considerably augmented by topical
capsaicinoids-containing patch in carrageenan-induced paw oedema of rat.
(PMID:23794063)
Abstract
Citations
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Ercan N, Uludag MO, Agis ER, Demirel-Yilmaz E
Department of Pharmacology, Faculty of Pharmacy, Gazi University, Etiler, 06330, Ankara,
Turkey.
Inflammopharmacology [2013, 21(6):413-419]

DOI: 10.1007/s10787-013-0175-7
Abstract
Highlight Terms
Diseases(2)
Species(1)
Chemicals(6)
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in musculoskeletal
disorders, but their systemic adverse effects limit their therapeutic benefit in local inflammation.
On the other hand, topical preparations of capsaicinoids are widely used for musculoskeletal
disorders as a complementary therapy. In this study, the effects of both topical capsaicinoidscontaining patch and local subcutaneous capsaicin application on the anti-inflammatory action
of NSAID were examined.Carrageenan-induced paw oedema of rats was used as the
inflammation model. The volume and weight of the paw oedema and plasma extravasation in the
paw were determined after carrageenaninjection. The systemic application of diclofenac (3
mg/kg), which is an NSAID, significantly decreased the volume and weight of the paw oedema.
Topical capsaicinoids-containing patch application or local capsaicin injection (2, 10, 20
g/paw) alone did not cause any effect on oedema volume and weight. However, the
combination of diclofenac with topical capsaicinoids-containing patch significantly increased
the effectiveness of diclofenac on inflammation. Evans blue content of the paws that represents
plasma extravasation was decreased by capsaicinoids-containing patch with and
without diclofenac and diclofenac combination with the lowest dose of capsaicin injection. The
results of this study indicate that topical application of capsaicinoids-containing patch enhances
the anti-inflammatory effect of diclofenac and its beneficial effect may not purely relate to
its capsaicincontent. In the treatment of local inflammatory disorders, the combination
of NSAID with topicalcapsaicinoids-containing patch could increase the anti-inflammatory
efficiency of drug without systemic side effects.
26.Systematic review: hepatotoxic events associated with herbal medicinal products.
(PMID:12950418)
Pittler MH, Ernst E
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth,
Exeter, UK. M.H.Pittler@exeter.ac.uk
Alimentary Pharmacology & Therapeutics [2003, 18(5):451-471]
Type: Journal Article, Review, Research Support, Non-U.S. Gov't
DOI: 10.1046/j.1365-2036.2003.01689.x
Abstract
Highlight Terms
Gene Ontology(1)
Diseases(1)
BACKGROUND: Large proportions of patients use herbal medicinal products, and encouraging
data in terms of effectiveness exist for some of these. One aspect, however, which is still largely
under-investigated is the question of potential harm. AIM: To review the recent evidence on
hepatotoxic events associated with the use of herbal medicinal products.
METHODS: Systematic literature searches were performed on Medline, Embase, The Cochrane
Library, Amed and Ciscom. To identify additional data, searches were conducted by hand in
relevant medical journals and in our own files. The screening and selection of articles and the
extraction of data were performed independently by the two authors. There were no restrictions
regarding the language of publication. In order to be included articles were required to report
data on hepatotoxic events associated with the therapeutic use of herbal medicinal products.
RESULTS: Single medicinal herbs and combination preparations are associated with
hepatotoxic events. Clinically, the spectrum ranges from transient elevations of liver enzyme
levels to fulminant liver failure and death. In most instances hepatotoxic herbal constituents are
believed to be the cause, while others may be due to herb-drug interactions, contamination
and/or adulteration.
CONCLUSIONS: A number of herbal medicinal products are associated with serious
hepatotoxic events. Incidence figures are largely unknown, and in most cases a causal attribution
is not established. The challenge for the future is to systematically research this area, educate all
parties involved, and minimize patient risk.
27.Pharmacological evaluation of mangiferin herbosomes for antioxidant and hepatoprotection
potential against ethanol induced hepatic damage.
(PMID:23167243)
Jain PK, Kharya M, Gajbhiye A
Department of Pharmaceutical Sciences, Dr Hari Singh Gour Central University , Sagar, Madhya
Pradesh , India.
Drug Development and Industrial Pharmacy [2013, 39(11):1840-1850]
Type: Journal Article, Research Support, Non-U.S. Gov't, Comparative Study, In Vitro
DOI: 10.3109/03639045.2012.738685
Abstract
Highlight Terms
Diseases(4)
Genes/Proteins(6)
Species(1)
Chemicals(9)
CONTEXT: Fatty liver is the first stage of alcoholic damage which is reversible with abstinence
from alcohol. Mangiferin (MF) showed potent scavenging activity on diphenyl-1-picrylhydrazyl
radicals which stimulate liver regeneration in various liver injuries. OBJECTIVE: Although, MF
shows hepatoprotection against various liver disorders but due to rapid clearance and limited
solubility in lipoid environment, there is problem of its poor absorption from intestine hence
poor bioavailability. Owing to which there is a need to develop MF herbosomes to resolve the
problem of poor bioavailability to enhance the therapeutic potential.

METHODS: Successfully prepared MF herbosomes through complexation
with phospholipids were characterized by physicochemical, chromatography, spectroscopy
(differential scanning calorimetry (DSC), infrared (IR), and nuclear magnetic resonance
(NMR)), ex vivo absorption using everted small intestine sac technique and in vivo studies
using ethanol inducing hepatotoxicity in albino rats and comparing the results against plain MF.
RESULTS: Ex vivo study showed significant increased absorption of MF from prepared MF
herbosomes as compared to plain MF. The hepatoprotective potential of MF herbosomes
evaluated by in vivo study revealed significantly decreased levels of
serum glutamate oxaloacetate transminase (SGOT), serum glutamate pyruvate transminase
(SGPT), total bilirubin, and alkaline phosphatase(ALP) in MF herbosomes as compared to plain
MF. MF herbosomes also showed significantly decreased level of malonyl dehydrogenase along
with increased levels of reduced glutathione,superoxide dismutase (SOD) and catalase as
compared to plain MF which was also comparable to the standard drug, silymarin (SL).
CONCLUSION: The above mentioned results showed that hepatoprotective
and antioxidant potency of MF enhanced due to the preparation of its herbosomes.
28. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of
osteoarthritis knees: A Government of India NMITLI arthritis project.
(PMID:22529679)
Abstract
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Chopra A, Saluja M, Tillu G, Venugopalan A, Narsimulu G, Sarmukaddam S, Patwardhan B
Centre for Rheumatic Diseases, Pune, Maharashtra, India.
Journal of Ayurveda and Integrative Medicine [2012, 3(1):38-44]
DOI: 10.4103/0975-9476.93948
Abstrac
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Diseases(3)
Genes/Proteins(1)
Species(5)
Chemicals(1)
BACKGROUND: Results of an exploratory trial suggested activity trends of Zingiber
officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment

of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania
somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale"
(formulation C). This paper reports safety of these formulations when used in higher doses (1.52 times) along with Sallaki Guggul and Bhallataka Parpati
(a Semecarpus anacardium preparation).
MATERIALS AND METHODS: Ninety-two patients with symptomatic OA knees were
enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug
trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform
combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was
carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered
information. Laboratory evaluation included detailed hematology and metabolic parameters.
Patients were examined at baseline, first and fourth weeks, and on completion. Standard
statistical program (SPSS version 12.5) was used for analysis.
RESULTS: None of the patients reported serious AE or withdrew due to any drug-related
toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver
enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic
transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group
IV). Other laboratory parameters remained normal. The mean improvement in active pain visual
analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI
0.22-2.5), and urinary C-TAX (cartilagecollagen breakdown product) assay was maximum (NS)
in group IV. Lower dose group I showed numerically superior improvement compared with
higher dose group II.
CONCLUSION: The results suggested that despite higher doses, standardized Ayurvedic
formulations demonstrated a good safety profile. An improved efficacy and likely
chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with
adequate power and sample size was planned based on the learning from this trial.
29. Ayurvedic formulation of Liv-Pro-08 reduces nonalcoholic fatty liver disease in rats fed with
high-fat diet.
(PMID:22196506)
Suriyavathana Vedanarayanan M, Krishnan N
Department of Biochemistry, Periyar University, Tamilnadu, India. suriyaveda@yahoo.co.in
Journal of Acupuncture and Meridian Studies [2011, 4(4):236-241]
DOI: 10.1016/j.jams.2011.09.014
Abstrac
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Diseases(2)
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Chemicals(3)
Nonalcoholic fatty liver disease (NAFLD) has emerged as a serious obesity-related disorder, and
it will continue to be a major liver health issue worldwide in the coming decades. We aimed to
determine the effect of Liv-Pro-08 (Nigella sativa, Entada pursaetha, and Ficus glomerata) an
oral ayurvedic formulation on rats fed with high-fat diet. Rats were given a high-fat diet for a
period of 7 days. After this period, Liv-Pro-08 (250, 500, and 750 mg/kg.body weight was given
orally for 7 days. We examined the effect of the high-fat diet on various parameters related
to obesity and insulinresistance. In the experimental rats who received the extract of Liv-Pro-08,
their lipoprotein profiles were significantly improved compared with those that are not receiving
the extract. Also, a slight reduction was observed in serum aspartate aminotransferase,
alanine aminotransferase, and alkaline phosphatase enzymes. Moreover, Liv-Pro-08
significantly decreased their fasting serum glucose and fasting insulin levels. This experimental
study suggests that Liv-Pro-08 can act as a therapeutic tool in preventing NAFLD progression
(i.e., reducing hepatic lipid accumulation). Although further investigations and large randomized
trials should be conducted, ayurvedic Liv-Pro-08 oral formulation may be a potential natural
drug for NAFLD in the future.
30. Emblica officinalis protects against alcohol-induced liver mitochondrial dysfunction in rats.
(PMID:19459733)
Reddy VD, Padmavathi P, Varadacharyulu NCh
Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, India.
Journal of Medicinal Food [2009, 12(2):327-333]
DOI: 10.1089/jmf.2007.0694
Abstract
Highlight Terms
Gene Ontology(1)
Genes/Proteins(7)
Species(2)
Chemicals(10)
The protective effect of Emblica officinalis, a commonly used botanical in many Ayurvedic
preparations, was investigated for its effects on liver mitochondria of ethanol-administered rats.
Oxidative stress and reactive oxygen species-mediated toxicity are considered two of the key
underlying mechanisms responsible for alcohol-induced liver injury and mitochondrial
dysfunction. Alcohol-administered rats showed a significant elevation of plasma transaminases
(aspartate and alanine aminotransferases), alkaline phosphatase, and gammaglutamyl transferase compared to control rats. However, activities of hepatic
mitochondrial antioxidant enzymes, viz., superoxide dismutase, glutathione peroxidase, and
reduced glutathione, were significantly lower. Chronic alcohol feeding also
increased lipid peroxide levels, protein carbonyl content, and overproduction of

nitricoxide followed by lowered activities of NADH dehydrogenase, succinate dehydrogenase
(SDH), andcytochrome c oxidase and content of cytochromes. Administration of E.
officinalis fruit extract (EFE) at a dose of 250 mg/kg of body weight/day to alcoholic rats offers
protection by simultaneously lowering the carbonyl content and lipid peroxidation and
elevating antioxidant enzyme activities, SDH,NADH dehydrogenase, and cytochrome c oxidase
activities, and content of cytochromes in hepatic mitochondria. Our data indicate
that EFE administration to chronically alcohol-fed rats offers protection against alcohol-induced
alterations. The active tannoid principles and nitric oxide scavenging compounds present
in EFE may have contributed to the protection observed.
31. Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum. et Thonn. on
aflatoxin B1-induced liver damage in mice.
(PMID:17720339)
Naaz F, Javed S, Abdin MZ
Centre for Transgenic Plant Development, Department of Biotechnology, Faculty of Science,
Jamia Hamdard, New Delhi 110062, India.
Journal of Ethnopharmacology [2007, 113(3):503-509]
DOI: 10.1016/j.jep.2007.07.017
Abstract
Highlight Terms
Gene Ontology(2)
Genes/Proteins(7)
Species(4)
Chemicals(5)
Phyllanthus amarus Schum. et Thonn. (Bhuia amla; Euphorbiacae) is a herb common to central
and southern India. It is an ayurvedic herb and has a wide range of traditional uses in different
diseases. The aim of this work was to evaluate the hepatoprotective effect of ethanolic extract
of Phyllanthus amarus (Phyllanthus amarus) on aflatoxin B(1)-induced liver damage
in mice using different biochemical parameters and histopathological studies. Aflatoxin was
administered orally (66.6 microg kg(-1)BW 0.2 ml(-1)day(-1)) to the mice of each group except
control to which normal saline andascorbic acid (0.1g kg(-1)BW 0.2 ml(-1)day(-1)) were given,
respectively. Ethanolic extract ofPhyllanthus amarus (0.3g kg(-1)BW 0.2 ml(-1)day(-1)) was
given to all groups except control groups (gp. I and gp. V) after 30 min
of aflatoxin administration. The entire study was carried out for 3 months and animals were
sacrificed after an interval of 30 days till the completion of study. Phyllanthus amarus extract
was found to show hepatoprotective effect by lowering down the content ofthiobarbituric
acid reactive substances (TBARS) and enhancing the reduced glutathione level and the activities
of antioxidant enzymes, glutathione peroxidase (GPx), glutathione-Stransferase (GST),superoxide dismutase (SOD) and catalase (CAT). Histopathological analyses
of liver samples also confirmed the hepatoprotective value and antioxidant activity of the
ethanolic extract of the herb, which was comparable to the standard antioxidant, ascorbic acid.
The overall data indicated thatPhyllanthus amarus possesses a potent protective effect
against aflatoxin B(1)-induced hepatic damage, and the main mechanism involved in the
protection could be associated with its strong capability to reduce the intracellular level of
reactive oxygen species by enhancing the level of both enzymatic and nonenzymatic antioxidants.
32. Traditional Indian systems of medicine.
(PMID:10748962)
Lodha R, Bagga A
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Annals of the Academy of Medicine, Singapore [2000, 29(1):37-41]
Abstrac
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Gene Ontology(1)
Diseases(7)
Genes/Proteins(1)
Species(2)
Chemicals(3)
INTRODUCTION: A number of traditional systems of medicine exist in India of which

Ayurveda is the most popular. Despite being in use for more than 3000 years, few properly
designed trials have scientifically examined the clinical potential of Ayurvedic and other
medications.
METHODS: We reviewed the MEDLINE database to identify clinical trials conducted using
traditional Indian medicines. Single case reports were excluded.
RESULTS: Ayurvedic preparations have been successfully used for the treatment of bronchial
asthma, ischaemic heart disease and hyperlipidaemia. Formulations containing curcumin were
reported to reduce inflammation and disability in double-blind clinical trials on patients
with rheumatoid arthritis. A number of products are reported to be useful in patients with acute
viral hepatitis. A multicentric study by the Indian Council of Medical Research showed that a
preparation fromPterocarpus marsupium was effective in reducing levels of blood glucose and
glycosylatedhaemoglobin in patients with non-insulin-dependent diabetes mellitus. In another
multicentric trial, patients with fistula-in-ano were randomised to surgery or application of
medicated seton (Ksharsootra). Surgical treatment led to a faster cure but recurrence rates were
lower with medicated seton. Administration of extract from Bacopa monnieri, to children
with mental retardation, was reported to significantly improve short-term and long-term
memory.
CONCLUSIONS: Evidence-based studies on the efficacy and safety of traditional Indian
medicines are limited. The essential ingredient in most formulations is not precisely defined.
High quality studies are necessary to evaluate and compare the value of traditional Indian drugs
to modern medicine.
33. Hepatoprotective action of abhrak bhasma, an ayurvedic drug in albino rats against hepatitis
induced by CCl4.
(PMID:11883510)
Buwa S, Patil S, Kulkarni PH, Kanase A
Department of Zoology, Shivaji University, Kolhapur, India.
Abstract
Highlight Terms
Diseases(2)
Genes/Proteins(2)
Species(1)
Chemicals(2)
Abhrak bhasma is a commonly used ayurvedic drug against many diseases including hepatitis. It
is tested in albino rats using a model of hepatitis induced by a single dose of CCl4 (3 ml/kg body
wt). Different doses of abhrak bhasma (10, 20, 30 and 40 mg/kg body wt) were tested to decide
the dose related hepatoprotective efficacy. The centrolobular necrosis induced by single dose
of CCl4 was reduced significantly by abhrak bhasma (10 mg) and liver histology was also
protected by 20 mg dose. Liver acid lipase activity was lowered, while alkaline
and lipoprotein lipase activities were elevated due to treatment of single dose of CCl4. Abhrak
bhasma counteracted the action of CCl4 on liver lipolytic enzymes. CCl4 did not alter the
kidney histologically. Activities of three lipases of rat kidney (acid, alkaline
and lipoprotein lipases) were reduced by CCl4 treatment and were reversed by administration of
abhrak bhasma. Acid lipase activity of rat adipose tissue was reduced by CCl4 treatment. On the
contrary alkaline, lipoprotein and hormone sensitive lipases were enhanced after 24 hr of
administration of CCl4. Acid lipase activity was raised by administration of different doses of
abhrak bhasma concurrent with CCl4. Abhrak bhasma treatment along with CCl4 enhanced
alkaline lipaseactivity at 10 and 20 mg dose and later it was reduced at 30 and 40 mg doses and
came to normal levels. Lipoprotein and hormone sensitive lipases were reduced by the
counteraction of increasing doses of abhrak bhasma.
34. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent--experimental &
clinical studies.
(PMID:9715310)
Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh V, Vora PV, Perissond D, Baxi AJ, Kale
PM
Ciba Research Centre, Goregaon, Bombay.
Journal of Postgraduate Medicine [1996, 42(4):105-108]
Type: Clinical Trial, Journal Article, Randomized Controlled Trial

Abstrac
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Diseases(2)
Genes/Proteins(2)
Species(2)
Chemicals(3)
Picrorhiza kurroa (Pk), a known hepatoprotective plant, was studied in experimental and clinical
situtations. The standardization of active principles--Picroside 1 and 2 was done with High
Performance Liquid Chromatography. Picroside 1 ranged from 2.72 to 2.88 mg/capsule and
picroside 2 from 5.50 to 6.00 mg/capsule. In the galactosamine-induced liver injury in rats, Pk at
a dose of 200 mg/kg p.o. showed a significant reduction (p < 0.05) in liver lipid content, GOT
and GPT. In a randomised, double-blind placebo controlled trial in patients diagnosed to
have acute viral hepatitis(HBsAg negative), Pk root powder 375 mg three times a day was given
for 2 weeks (n = 15) or a matching placebo (n = 18) was given. Difference in values of bilirubin,
SGOT and SGPT was significant between placebo and Pk groups. The time in days required for
total serum bilirubin to drop to average value of 2.5 mg% was 75.9 days in placebo as against
27.44 days in Pk group. The present study has shown a biological plausability of efficacy of Pk
as supported by clinical trial in viral hepatitis, hepatoprotection in animal model and an
approach for standardizing extracts based on picroside content.
35. Effect of hepatoprotective ayurvedic drugs on lipolytic activities during CCl4 induced acute
hepatic injury in albino rats.
(PMID:8500840)
Patil S, Kanase A, Varute AT
Zoology Department, Shivaji University, Kolhapur, India.
Abstract
Highlight Terms
Diseases(1)
Genes/Proteins(2)
Species(1)
Chemicals(2)
Daily treatment of CCl4(3 ml/kg body wt) for 7 days induced acute hepatic necrosis in
albino rats. Treatment of CCl4 caused significant alterations in the activities of acid lipase,
alkaline lipase,lipoprotein lipase of liver, kidney and adipose tissue and hormone sensitive
lipase of adipose tissue of albino rat. Administration of hepatoprotective ayurvedic drugs
(kumari asav, kumari kalp, arogyavardhini and tamra bhasma) concomitant
with CCl4 counteracted the action of CCl4 on lipolytic enzymes exhibiting hepatoprotection.
The possible physiological significance of alterations in lipolytic enzymes during hepatic
necrosis induced by CCl4 and hepatoprotection by the above ayurvedic drugs is discussed.
36. Modernization of Ayurveda: a brief overview of Indian initiatives.

(PMID:24689312)
Mukherjee A, Banerjee M, Mandal V, Shukla AC, Mandal SC
Natural Product Communications [2014, 9(2):287-290]
Abstract
Highlight Terms
Gene Ontology(1)
Species(2)
Ayurveda has been the main guiding force in drug discovery from traditional medicine. In
concept, this system is rooted in folk or ethnomedicine and in practice it shows further
refinement and developmentin accordance with local traditions. Isolation of active principles
from crude drugs, their pharmacological evaluation, therapeutic proving and clinical application
resulted in the genesis of modem or so called allopathic medicine. To keep the opportunity alive
for further development in traditional as well as modem medicines, it is necessary to have an
uninterrupted connection with ethnomedicine. Since the practice of ethnomedicine is based on
the age-long indigenous knowledge which has been orally transmitted through generations and
sustained in traditions there is an urgent need to document such knowledge. The ongoing
strategies adopted in India to document the precious traditional knowledge and conserve
medicinal plants are discussed in this communication. India with her rich plant wealth and
traditional knowledge about the medicinal use of plants has tremendous scope to provide
leadership in ensuring human health and longevity.
37.
A review of plants used in the treatment of liver disease: part 1.
(PMID:9855566)
Luper S
Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA.
lupers@cwix.com
Alternative Medicine Review : a Journal of Clinical Therapeutic [1998, 3(6):410-421]
Abstract
Highlight Terms
Diseases(5)
Species(5)
Chemicals(1)
Botanicals have been used traditionally by herbalists and indigenous healers worldwide for the
prevention and treatment of liver disease. Clinical research in this century has confirmed the
efficacy of several plants in the treatment of liver disease. Basic scientific research has
uncovered the mechanisms by which some plants afford their therapeutic effects. Silybum
marianum (milk thistle) has been shown to have clinical applications in the treatment of
toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis via its
antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, immunomodulating, and
liver regenerating effects. Picrorhiza kurroa, though less well researched than Silybum, appears
to have similar applications and mechanisms of action. When compared with Silybum, the
hepatoprotective effect of Picrorhiza was found to be similar, or in many cases, superior to the
effect of Silybum.
38. Herbal medicines for liver diseases.
(PMID:16187178)
Dhiman RK, Chawla YK
Department of Hepatology, Postgraduate Institute of Medical Education and Research,
Chandigarh, 160012, India. rkpsdhiman@hotmail.com
Digestive Diseases and Sciences [2005, 50(10):1807-1812]
DOI: 10.1007/s10620-005-2942-9
Abstract
Highlight Terms
Gene Ontology(1)
Diseases(7)
Genes/Proteins(1)
Species(5)
Herbal medicines have been used in the treatment of liver diseases for a long time. A number of
herbal preparations are available in the market. This article reviews four commonly used herbal
preparations: (1) Phyllanthus, (2) Silybum marianum (milk thistle), (3) glycyrrhizin
(licorice root extract), and (4) Liv 52 (mixture of herbs). Phyllanthus has a positive effect on
clearance of HBVmarkers and there are no major adverse effects; there are no data from
randomized controlled trials on clinically relevant outcomes, such as progression of chronic
hepatitis to cirrhosis and/or liver cancer, and on survival. Silymarin does not reduce mortality
and does not improve biochemistry and histology among patients with chronic liver disease;
however, it appears to be safe and well tolerated. Stronger neominophagen C (SNMC) is a
Japanese preparation that contains 0.2% glycyrrhizin, 0.1% cysteine, and 2% glyceine. SNMC
does not have antiviral properties; it primarily acts as an anti-inflammatory or cytoprotective
drug. It improves mortality in patients with subacute liver failure and improves liver functions in
patients with subacute hepatic failure, chronic hepatitis, and cirrhosis with activity. SNMC does
not reduce mortality among patients with cirrhosis with activity. SNMC may prevent
thedevelopment of hepatocellular carcinoma in patients with chronic hepatitis C, however,
prospective data are lacking. Liv 52, an Ayurvedic hepatoprotective agent, is not useful in the
management of alcohol-induced liver disease. Standardization of herbal medicines has been a
problem and prospective, randomized, placebo-controlled clinical trials are lacking to support
their efficacy. The methodological qualities of clinical trials of treatment with herbal
preparations are poor. The efficacy of these herbal preparations need to be evaluated in
rigorously designed, larger randomized, double-blind, placebo-controlled multicenter trials.

39. Beneficial drugs for liver diseases.
(PMID:17966118)
Muriel P, Rivera-Espinoza Y
Departamento de Farmacologa, Cinvestav-IPN, Apdo. Postal 14-740. Mxico 07000, D.F.
Mxico. pamuriel@cinvestav.mx
Journal of Applied Toxicology : JAT [2008, 28(2):93-103]
DOI: 10.1002/jat.1310
Abstract
Highlight Terms
Diseases(3)
Species(2)
Chemicals(6)
Liver diseases are a major problem of worldwide proportions. However, the number of drugs
actually used successfully in humans is very small. In this review some of the most
promising/studied drugs utilized for liver diseases were chosen and analysed critically from the
basic to the clinical point of view. Antiviral agents are not discussed because excellent reviews
have appeared on this topic. The compounds/preparations described herein are,
alphabetically: colchicine, corticosteroids, curcumin, glycyrrhizin, interferons (for their
antifibrotic properties), Liv 52, nitric oxide, resveratrol, silymarin, sulfoadenosylmethionine,
and thalidomide. Colchicine and corticosteroids have been studied extensively
in animals and humans; most clinical studies suggest that these compounds are not useful in the
treatment of liver diseases. Glycyrrhizin is an herbal medicine with several components that has
interesting hepatoprotective properties in patients with subacute liver failure but deserves more
prospective controlled trials. Interferon has shown interesting antifibrotic properties
in animalsand humans; prospective studies on their antifibrotic/fibrolytic activity are
required. Curcumin,resveratrol and thalidomide are very attractive newly discovered protective
and curative compounds on experimental hepatic diseases. Their mechanism of action is
associated with the ability to down-regulate NF-kappaB and to decrease pronecrotic and
profibrotic cytokines. Unfortunately, clinical studies are lacking. Sulfoadenosylmethionine and
silymarin are also promising drugs utilized mainly incholestasis but the benefits can be
expanded if more controlled trials are performed. The future is to carry out controlled
prospective double-blind multicenter studies with the newly discovered drugs with proven
beneficial effects on animals. Fundamental hepatobiology should also be encouraged.
40. Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma
LoVo cells in culture and tumor xenograft.
(PMID:19638451)
Abstract
Citations
BioEntities
Related Articles
External Links
Kaur M, Velmurugan B, Tyagi A, Deep G, Katiyar S, Agarwal C, Agarwal R
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado-Denver,
Aurora, Colorado 80045, USA.
Molecular Cancer Therapeutics [2009, 8(8):2366-2374]
Type: Journal Article, Research Support, N.I.H., Extramural
DOI: 10.1158/1535-7163.MCT-09-0304
Abstrac
t
Highlight Terms
Gene Ontology(6)
Diseases(3)
Genes/Proteins(5)
Species(2)
Chemicals(1)
Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. The use
of nontoxic phytochemicals in the prevention and intervention of colorectal cancer has been
suggested as an alternative to chemotherapy. Here we assessed the anticancer efficacy of
silibinin against advanced colorectal cancer LoVo cells both in vitro and in vivo. Our results
showed that silibinin treatment strongly inhibits the growth of LoVo cells (P < 0.05-0.001) and
induces apoptotic death (P < 0.01-0.001), which was associated with increased levels of cleaved
caspases (3 and 9) and cleaved poly(ADP-ribose) polymerase. Additionally, silibinin caused a
strong cell cycle arrest at G(1) phase and a slight but significant G(2)-M-phase arrest at highest
concentration (P < 0.01-0.001). Molecular analyses for cell cycle regulators showed that
silibinin decreases the level of cyclins (D1, D3, A and B1) and cyclin-dependent kinases (1, 2, 4,
and 6) and increases the level of cyclin-dependent kinase inhibitors (p21 and p27). Consistent
with these results, silibinin treatment also decreased
thephosphorylation of retinoblastoma protein at Ser(780), Ser(795), and Ser(807)/Ser(811) sites
without significantly affecting its total level. In animal studies, oral administration of silibinin
for 6 weeks (at 100 and 200 mg/kg/d for 5 days/wk) significantly inhibited the growth of LoVo
xenograft (P < 0.001) in athymic nude mice without any apparent toxicity. Analyses of xenograft
tissue showed that silibinin treatment inhibits proliferation and increases apoptosis along with a
strong increase in p27 levels but a decrease in retinoblastoma phosphorylation. Together, these
results suggest the potential use of silibinin against advanced human colorectal cancer.
41. Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of
Drugs for the Treatment of {beta}-Thalassemia and Sickle-Cell Anemia.
(PMID:18955291)
Bianchi N, Zuccato C, Lampronti I, Borgatti M, Gambari R
GenTech-for-Thal, Laboratory for the Development of Pharmacological and Pharmacogenomic

Therapy of Thalassaemia, Biotechnology Centre, Ferrara, Italy. gam@unife.it.
Evidence-based Complementary and Alternative Medicine : ECAM [2009, 6(2):141-151]
DOI: 10.1093/ecam/nem139
Abstract
Highlight Terms
Diseases(1)
Genes/Proteins(2)
Species(4)
Chemicals(7)
The objective of this review is to present examples of lead compounds identified from biological
material (fungi, plant extracts and agro-industry material) and of possible interest in the field of
a pharmacological approach to the therapy of beta-thalassemia using molecules able to stimulate
production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as
potential drugs for pharmacological treatment of beta-thalassemia, the following conclusions
can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters
exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still
limited) employing HbF inducers were effective in ameliorating the symptoms of betathalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis
and gamma-globin mRNA accumulation indicates that in vitro testing might be predictive of in
vivo responses and (iv) combined use of different inducers might be useful to maximize HbF,
both in vitro and in vivo. In this review, we present three examples of HbF inducers from the
natural world: (i) angelicin and linear psoralens, contained in plant extracts
from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, apolyphenol found in grapes
and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus.
42. Recent advances in herbal medicine for treatment of liver diseases.
(PMID:21595500)
Ghosh N, Ghosh R, Mandal V, Mandal SC
Dr. BC Roy College of Pharmacy and Allied Health Sciences, Durgapur, India.
nilanjanghosh81@yahoo.in
Pharmaceutical Biology [2011, 49(9):970-988]
DOI: 10.3109/13880209.2011.558515
Abstrac
t
Highlight Terms
Gene Ontology(2)
Diseases(3)
Genes/Proteins(3)
Species(1)
Chemicals(4)
CONTEXT: Liver disease is a serious ailment and the scenario is worsened by the lack of
precise therapeutic regimens. Currently available therapies for liver ailments are not apposite
and systemic toxicity inhibits their long term use. Medicinal plants have been traditionally used
for treating liver diseases since centuries as the toxicity factor appears to be on the lower
side. OBJECTIVE: Several phytochemials have been identified which have significant
hepatoprotective activity with minimal systemic adverse effects which could limit their long
term use. The scenario calls for extensive investigations which can lead to development of lead
molecules for hepatoprotective molecules of future. This review deals with the biological
activity, mode of action and toxicity and forthcoming application of some of these leads.
METHODS: These generally have strong antioxidative potential and cause induction
of antioxidantenzymes like superoxide dismutase, reduced glutathione and catalase. Additional
mechanisms of hepatoprotection include stimulation of heme oxygenase-1 activity, inhibition of
nitric oxide production, hepatocyte apoptosis and nuclear factor-B activation.
RESULTS AND CONCLUSION: Out of the several leads obtained from plant sources as
potential hepatoprotective agents, silymarin, andrographolide, neoandrographolide, curcumin,
picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have been established as
potent hepatoprotective agents. The hepatoprotective potential of several herbal medicines has
been clinically evaluated. Significant efficacy has been seen with silymarin, glycyrrhizin and
Liv-52 in treatment of hepatitis, alcoholic liver disease and liver cirrhosis.
44. se of complementary and alternative medicine in patients with liver disease.
(PMID:12358262)
Strader DB, Bacon BR, Lindsay KL, La Brecque DR, Morgan T, Wright EC, Allen J, Khokar
MF, Hoofnagle JH,Seeff LB
Division of Gastroenterology, Hepatology and Nutrition, Veterans Affairs Medical Center,
Washington, DC 20422, USA.
The American Journal of Gastroenterology [2002, 97(9):2391-2397]
DOI: 10.1111/j.1572-0241.2002.05993.x
Abstract
Highlight Terms
Diseases(2)
Genes/Proteins(1)
OBJECTIVES: Complementary and alternative medicine (CAM) is used by 42% of the U.S.
population. Its use among patients with chronic liver disease has not been well defined. Toward
that end, we surveyed patients in six geographically diverse liver disease clinics in the United
States for use of CAM.
METHODS: Patients attending six liver disease clinics were polled via a common questionnaire
regarding their use of CAM. Demographic information was obtained to identify predictors
of CAM use. Statistical analysis included univariate and multivariate analysis using logistic
regression.
RESULTS: A total of 989 patients completed the questionnaire. Of these, 389 (39%) admitted to
using some form of CAM at least once during the preceding month; 21% admitted to using
herbal preparations, and 13% used herbs to treat their liver disease. Five variables were found to
be predictive of alternative therapy use: female sex, young age, level of education, annual
income, and geographic location. In all, 74% of patients reported using CAM in addition to the
medications prescribed by their physician, but 26% did not inform their physician of
their CAM use. CONCLUSIONS: CAM use is as common among patients visiting liver
disease clinics in the United States as in the general population (39% vs 42%). Many patients
are using herbs to treat their liver disease but are declining to discuss this use with their
physician.
45.New leads for liver disease treatments

Tuesday 5 August 2014 - 12am PST http://www.medicalnewstoday.com/releases/280503.php
Much of the liver's metabolic function is governed by circadian rhythms - our own body clock - and UC
Irvine researchers have now found two independent mechanisms by which this occurs.
The study, published online in Cell, reveals new information about the body clock's sway over metabolism
and points the way to more focused drug treatments for liver disease and such metabolic disorders
as obesity and diabetes.
Paolo Sassone-Corsi, UCI's Donald Bren Professor of Biological Chemistry, and postdoctoral scholar
Selma Masri report that two of these circadian-linked proteins, SIRT1 and SIRT6, manage important liver
processes - lipid storage and energy usage in liver cells - separately and distinctly from each other.
This surprising discovery of genomic partitioning, Masri noted, reveals how strictly regulated circadian
control of metabolism can be.
"The ability of the genome and epigenome to cross-talk with metabolic pathways is critical for cellular and
organismal functions. What's remarkable is that the circadian clock is intimately involved in this dialogue,"
she said.
Circadian rhythms of 24 hours govern fundamental physiological functions in virtually all organisms. The
circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes
and adapt themselves to the appropriate time of day. Changes to these rhythms can profoundly influence
human health. Up to 15 percent of people's genes are regulated by the day-night pattern of circadian
rhythms; nearly 50 percent of those involved with metabolic pathways in the liver are influenced by these
rhythms.
SIRT1 and SIRT6 belong to a group of proteins called sirtuins that participate in epigenetic control of the
genome and help regulate important biological processes ranging from cell health maintenance to lipid
storage and energy expenditure in cells. They're widely studied for their effect on metabolism and
longevity.
To discover how SIRT1 and SIRT6 work independently of each other, Masri and Sassone-Corsi conducted
tests with two sets of mice - one with SIRT1 in the liver knocked out and the other with SIRT6 nullified.
The two sirtuins, the scientists learned, are committed to the control of distinct genomic domains, with
hundreds of genes being SIRT1-dependent and hundreds of others relying on SIRT6. This resulted in a
distinct partition of metabolic pathways and physiological functions, Sassone-Corsi said.
He added that these findings pave the way to further investigations that may facilitate the design of
pharmacological strategies targeting SIRT1- or SIRT6-specific metabolic functions and pathologies.
46. Scientists pinpoint channeling of cell's energy flow in

moving metal ions
Tuesday 24 June 2014 - 1am PST http://www.medicalnewstoday.com/releases/278630.php
Case Western Reserve University scientists have discovered how a family of proteins - cation diffusion
facilitators (CDFs) - regulates an important cellular cycle where a cell's energy generated is converted to
necessary cellular functions. The finding has the potential to inform future research aimed at identifying
ways to ensure the process works as designed and, if successful, could lead to significant breakthroughs in
the treatment of Parkinson's, chronic liver disease and heart disease.
The results of this research were posted online by the journal Nature and will be published in the print
edition at a later date.
"CDF is a major protein family type found in all forms of life," said senior author Mark R. Chance, PhD, the
Charles W. and Iona A. Mathias Professor of Cancer Research, Case Western Reserve University School
of Medicine. "Mutations or altered regulation of human CDFs modify the concentrations of metal ions
critical to cell function and are associated with key human diseases, including those affecting endocrine,
neurologic, hepatic and cardiovascular systems."
To understand how the cell cycle works, envision a gate to human cells that controls the flow of substances
necessary to maintain cell survival. When and how that gate opens and closes is critical to fundamental
cellular functions, and in turn, to human health. CDFs ensure the gate's seamless operation by controlling
the flow of metal ions as energy is cycled. In this investigation, Case Western Reserve scientists sought to
understand the intricate details of CDF molecular function and mechanisms of transport.
Chance and his colleagues studied a form of CDF found in bacteria where the protein YiiP functions like a
motor, using energy in the form of a gradient of protons (hydrogen atoms) to pump zinc ions out of cells.
While zinc is pushed successfully out of the cell, a flow of protons is pulled into it. A perfectly functioning
zinc-proton flow cycle, then, brings in protons, which the YiiP protein converts into conformational changes
in the protein structure. Those changes, in turn, send zinc out of the cell. If the CDF-regulated gate
controlling the zinc-proton cycle malfunctions, a range of diseases can result.
To visualize the zinc-proton cycle, Case Western Reserve scientists used sophisticated dynamic imaging
technology - the cellular cycle operates on time scales comparable to the blink of the eye. Dynamic
imaging involved a labeling system - x-ray-mediated hydroxyl radical footprinting - that recognizes water
molecules in transmembrane proteins. The scientists also used mass spectrometry, a powerful atom-andmolecule recognition technology, to study the labeled proteins. These technologies allowed investigators to
watch the YiiP protein in real time as it took up zinc atoms and rearranged its structure cycle through a
pumping sequence.
"Membrane proteins (including CDF) are some of the most important cellular drug targets, including Gprotein coupled receptors (GPCR), which represent 50 percent of the non-antibiotic drug market." Chance
said.
GPCRs are protein molecules that sense chemical signals outside the cell and then activate cellular
responses to these signals. Chance and his colleagues have studied GPCR structure and dynamics using
innovative mass spectrometry-based technology. In this more recent work on CDFs, a dynamic picture of
the membrane protein has emerged. It is a complex, but explainable, machine that uses a widely available
form of energy, the proton gradient, to carry out cellular functions.
"We have now produced high-resolution pictures of signal transmission and ion transport mechanisms for a
range of ion channels and GPCRs," Chance said. "Our work in CDFs is a visible example of the power of
these new technologies to solve important problems in the membrane protein field. We must continue to
examine CDFs to understand their mechanisms of action, especially in the context of drug effects on the
biochemical mechanisms of action."
47.Significant potential in treating hepatitis C with new Chinese

herbal medicine
Tuesday 15 April 2014 - 12am PST http://www.medicalnewstoday.com/releases/275473.php
Data from a late-breaking abstract presented at the International Liver Congres 2014 identifies a new
TM
compound, SBEL1, that has the ability to inhibit hepatitis C virus (HCV) activity in cells at several points in
the virus' lifecycle.[i]
SBEL1 is a compound isolated from Chinese herbal medicines that was found to inhibit HCV activity by
approximately 90%. SBEL1 is extracted from a herb found in certain regions of Taiwan and Southern
China. In Chinese medicine, it is used to treat sore throats and inflammations. The function of SBEL1
within the plant is unknown and its role and origins are currently being investigated.
Scientists pre-treated human liver cells in vitro with SBEL1 prior to HCV infection and found that SBEL1
pre-treated cells contained 23 percent less HCV protein than the control, suggesting that SBEL1 blocks
virus entry. The liver cells transfected with an HCV internal ribosome entry site (IRES)-driven luciferase
reporter that were treated with SBEL1 reduced reporter activity by 50% compared to control. This suggests
that that SBEL1 inhibits IRES-mediated translation, a critical process for viral protein production.
In addition, the HCV ribonucleic acid (RNA) levels were significantly reduced by 78 percent in HCV infected
cells treated with SBEL1 compared to the control group. This demonstrates that SBEL1 may also affect the
viral RNA replication process.
Prof. Markus Peck-Radosavljevic, Secretary-General of the European Association for the Study of the Liver
and Associate Professor of Medicine, University of Vienna, Austria, commented: "People infected with
hepatitis C are at risk of developing severe liver damage including liver cancer and cirrhosis. In the past,
less than 20 percent of all HCV patients were treated because the available treatments were unsuitable
due to poor efficacy and high toxicity. Recent advances means that we can now virtually cure HCV without
unpleasant side effects. However, the different virus genotypes coupled with the complexity of the disease
means there is still a major unmet need to improve options for all populations."
Professor Peck-Radosavljevic continued: "SBEL1 has demonstrated significant inhibition of HCV at
multiple stages of the viral lifecycle, which is an exciting discovery because it allows us to gain a deeper
understanding of the virus and its interactions with other compounds. Ultimately this adds to our library of
knowledge that may bring us closer to improving future treatment outcomes."
HCV invades cells in the body by binding to specific receptors on the cell, enabling the virus to enter it.2
Once inside, HCV hijacks functions of the cell known as transcription, translation and replication, which
enables HCV to make copies of its viral genome and proteins, allowing the virus to spread to other sites of
the body.2 When HCV enters the host cell, it releases viral (+)RNA that is transcribed by viral RNA
replicase into viral (-)RNA, which can be used as a template for viral genome replication to produce more
(+) RNA or for viral protein synthesis. Once the viral RNA is transcribed, HCV initiates a process known as
IRES-mediated translation, which allows the viral RNA to be translated into proteins by bypassing certain
protein translation checkpoints that would normally be required by the host cell to start protein translation.
[ii],[iii] Viral RNA is the genetic material that gives HCV its particular characteristics. This process enables
the virus to take advantage of the host cell's protein translation machinery for its own purposes.
There are an estimated 150 million to 200 million people living with chronic HCV and more than 350,000
people die annually from HCV-related diseases.[iv] HCV is transmitted through blood contact between an
infected individual and someone who is not infected. This can occur through needlestick injuries or sharing
of equipment used to inject drugs.[v]
48. Clinical Advances in Liver Disease -- What's New and

Where Are We Going?
http://www.medscape.org/viewarticle/494257
Introduction
This year's meeting of the American College of Gastroenterology (ACG) offered a dynamic venue for
the presentation of the latest information regarding issues in liver disease, with emphasis on topics in
epidemiology, pathophysiology, diagnosis, and treatment. This report discusses the key concepts
highlighted during these meeting proceedings, with a focus toward implications for clinical practice.
Hepatitis C
Presentations concerning hepatitis C virus (HCV) continue to dominate the sessions on liver disease
at national conferences, and this year's ACG meeting was no different.
Clinical Presentation, Disease Burden, and Resource Utilization

Two reports from a single gastroenterology practice in Michigan focused on the distribution of HCV
disease and its evaluation in an office setting. [1,2] Over a 5-year span, 670 patients with hepatitis C
were referred to the practice. In 2002 alone, patients with HCV accounted for 8% of all patient referrals
to the practice. Patients were largely white (80%) or black (15%), and most had abnormal liver function
tests (LFTs) (81%). The distribution of patient genotypes was typical of North American patients, with
74% having genotype 1 disease, 11% having genotype 2, 9% having genotype 3, and 2% having
genotype-4 infection. Of the 327 patients who underwent liver biopsy, 99% had some degree of
chronic inflammation and 72% had concomitant fibrosis. The presence of hepatic fibrosis correlated
with body mass index (BMI), but not with age, race, sex, or viral load. [1] The criterion for consideration
of liver biopsy in these patients was not identified.
A second abstract from the same group looked at utilization of practice resources in the care of HCV
patients.[2]Patients undergoing combination interferon plus ribavirin therapy had an average of 8.9
office visits compared with 2.8 visits for those individuals not treated. Office phone calls were also
monitored in the practice, identifying that a typical patient in this office logged a mean of 7.8 incoming
or outgoing calls during the 5-year study period, compared with 13 calls for treated HCV patients and
5.3 phone calls for untreated HCV patients. In addition, 140 of the patients with HCV underwent
endoscopic evaluation during the study period, including surveillance for varices and colorectal cancer.
This evaluation of patients with HCV in a private gastroenterology practice serves to identify the
increasing burden of patients with hepatitis C presenting for care in an urban gastroenterology
practice. The study authors also noted that the majority of patients referred for HCV care lacked much
HCV-specific assessment by the primary physician beyond more than the patient's anti-HCV and
LFTs. Additional testing of an anti-HCV-positive patient by the primary care physician, including a liver
enzyme profile, quantitative HCV level, and HCV genotype analysis, could help reduce the total costs
of care when referral to a consulting gastroenterologist is needed.
Noninvasive Method for Estimating Hepatic Fibrosis

In assessing patients for HCV treatment, the presence of underlying fibrosis is thought to identify the
patient who is at risk for continued progression of liver disease. Currently, this requires that a
percutaneous liver biopsy be obtained and graded for fibrosis and inflammation.
In a prospective study of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), Snyder
and colleagues,[3] from the University of Texas Medical Branch at Galveston, confirmed the correlation
of APRI with the simultaneous presence of fibrosis on liver biopsy, as reported earlier in a
retrospective analysis of patients by Wai and colleagues. [4] APRI (the product of the serum AST/the
upper limit of normal x 100, and then divided by the total platelet count) was calculated in 113 patients
undergoing liver biopsy to assess correlation with fibrosis and inflammation. Using the Ludwig-Batts
criteria, 63 patients had significant fibrosis on histology. When the degree of hepatic fibrosis was
compared with the APRI by multivariate regression, an APRI < 0.42 had a negative predictive value of
93% (25 of 27 patients correctly identified as having no fibrosis) and an APRI > 1.0 had a positive
predictive value for hepatic fibrosis of 96% (44 of 46 patients correctly predicted).
Does this mean that liver biopsy is no longer needed to assess patients for treatment with combination
pegylated interferon plus ribavirin therapy? Although many hepatologists will likely continue to rely on
histologic evidence of fibrosis to recommend treatment, the APRI may be a useful index for the patient
who refuses liver biopsy, and its use in this setting is encouraged. We must also continue to assess
predictive factors for the development of cirrhosis. Although fibrosis appears to be an indicator or risk
factor for cirrhosis, it is not yet clear that all patients who have mild fibrosis progress to end-stage liver
disease.
HCV Genotype-4 Disease

Khuroo and colleagues[5] performed a meta-analysis of 6 treatment trials of HCV genotype-4 disease
involving therapy with either combination pegylated interferon plus ribavirin or conventional interferon
plus ribavirin. They found that treatment with pegylated interferon plus ribavirin for 1 year was superior
to treatment with conventional interferon plus ribavirin. Subgroup analysis found that pegylated
interferon plus full-dose ribavirin was important to improve sustained response -- a 72% response was
achieved in patients receiving 1000-1200 mg ribavirin daily as compared with a 49% response in
patients receiving 800 mg ribavirin daily.
This study confirms that genotype-4 patients should receive 1 year of therapy and that full-dose
ribavirin based on weight is also needed.
Herbal Supplements
Side effects associated with treatment of HCV can be severe, and attempts by the patient or the
physician to control symptoms may have potential effects on response to therapy.
In a retrospective survey of patients who had been treated with interferon with or without ribavirin over
a 5-year period, it was observed that 64% of patients admitted to using herbal supplements during
therapy.[6] Although those patients who used supplements were slightly more likely to have symptoms
associated with treatment than those who did not, patients using herbal supplements were also more
likely to complete treatment (91%) when compared with patients who did not use them (78%).
This retrospective analysis reminds us that patients often use other medications and/or herbal
supplements during conventional medical treatments and that patients may or may not tell their
physicians about their use of such complementary substances. It is incumbent upon those providing
care to carefully ask each patient about alternative and conventional therapies during treatment for
any disorder.
Hemophiliac Patients With HCV Infection

HCV and HIV are common infections in patients with hemophilia. Because of the increased risk for
bleeding in hemophiliacs, there are few data available regarding the risk of percutaneous liver biopsy
in this population
In a retrospective review of patients with hemophilia who underwent liver biopsy, Lyons and
colleagues[7] confirmed that percutaneous liver biopsy after coagulation factor infusion is safe, and that
those patients with concomitant HIV infection are more likely to have significant fibrosis than
hemophiliac patients with HCV infection alone.
Clinical Course in Patients Receiving Antiviral Therapy for Recurrent HCV-Related Liver
Disease
Twenty-five percent to 40% of patients with chronic hepatitis C will develop end-stage liver disease,
some of whom will require liver transplantation. Unfortunately, the recurrence of hepatitis C infection in
the new graft is nearly universal, and many patients will require posttransplant therapy with
combination pegylated interferon and ribavirin. Because interferon is an immunomodulator, there has
been concern that treatment of post-liver transplant patients with interferon-based regimens might
increase the risk of allograft rejection. It has also been suggested that HCV infection may further
increase the risk of chronic allograft rejection in patients with recurrent HCV infection post
transplantation.
In a retrospective review[8] of 49 patients at the Duke University Medical Center who received
combination pegylated interferon plus ribavirin treatment for recurrent HCV post liver transplantation, 7
developed acute or chronic rejection while 12 achieved sustained viral clearance. This study suggests
that approximately 25% of patients with recurrent HCV infection post liver transplantation can achieve
clearance of HCV, whereas some will develop acute or chronic allograft rejection. Although this study
does not clarify the relationship between use of interferon and allograft rejection, it does identify the
need to carefully monitor the patient's liver studies and immunosuppression during therapy with
combination pegylated interferon and ribavirin.
Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease that can
lead to cirrhosis and hepatocellular carcinoma, and it is often associated with coexistent type 2
diabetes mellitus, obesity, and hyperlipidemia. Despite these known relationships, identifying the
patient with NASH can be difficult.
In an effort to determine whether LFTs, insulin and glucose levels, a measure of insulin resistance,
hepatic ultrasound data, and physical findings (such as waist circumference and BMI) could identify
patients with NASH, 365 consecutive patients who underwent gastric bypass surgery at the Geisinger
Clinic, Danville, Pennsylvania, had these measurements compared with liver histology obtained during
liver biopsy at surgery.[9] Ninety-five patients had histologic evidence of NASH, 4 of whom had
abnormal LFTs only; 45 had an abnormal ultrasound, 26 had both an abnormal ultrasound and
elevated LFTs, and 16 had a normal ultrasound and LFTs. There was no significant correlation with
insulin or glucose levels, or with physical findings observed. The only significant difference with
respect to these markers as a predictor of NASH was the observation of a lower mean glucose-toinsulin ratio in patients with NASH compared with patients with steatosis alone.
Thus, none of these factors could easily separate patients with NASH from those with only fatty liver.
NASH continues to be described in patients who may not have the typical associations of obesity and
type 2 diabetes mellitus. An index of suspicion plus histologic findings at liver biopsy may be the best
combination of tests available to the clinician at this time. Most important, clinicians need to continue
to assess the epidemiology of this disease in order to identify those associations that do lead to
progressive liver disease and cirrhosis.
Potpourri
The use of proton-pump inhibitor therapy after endoscopic variceal ligation is commonplace in clinical
practice to reduce ulcerations at the banding site. Shaheen and colleagues [10] performed a randomized,
double-blinded trial of pantoprazole vs placebo given after elective endoscopic variceal ligation. Their
findings confirmed that this proton-pump inhibitor reduced the size of ulceration postbanding, although
the total number of postbanding ulcers or of patient symptoms were not different between the 2 study
arms.[10]
What is the effect of the transjugular intrahepatic portosystemic shunt (TIPS) on thrombocytopenia
associated with liver cirrhosis? Sixty consecutive patients with a TIPS had platelet counts assessed
before and after undergoing procedure. Results showed that a significant increase in platelet count (at
least 20% higher) occurred in all patients, including those with severe thrombocytopenia. [11]
Supported by an independent educational grant from Novartis.
References
1. Shehab TM, Randawa R, Gunaratnam NT. Clinical presentation and disease burden in hepatitis C
patients referred to a private practice gastroenterology group: a five year experience (1997-2002) with
670 patients. Am J Gastroenterol. 2004;99:S74. [Abstract #225]
2. Shehab TM. Office based resource utilization and endoscopic resource utilization in the care of hepatitis
C patients in a private practice gastroenterology group. Am J Gastroenterol. 2004;99:S238. [Abstract
#736]
3. Snyder N, Gajula L, Finlay D, et al. The APRI is a good predictor of fibrosis in HCV, and may be
enhanced by the insulin resistance index (HOMA-IR). A prospective study. Am J Gastroenterol.
2004;99:S100. [Abstract #310]
4. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis
and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518-526.
5. Khuroo MS, Khuroo MS, Dahab ST, et al. Peginterferon plus ribavirin for the initial treatment of chronic
hepatitis C genotype 4: a meta-analysis of randomized trials. Am J Gastroenterol. 2004;99:S100.
[Abstract #308]
6. Prasad S, Naram S, Kancherla VK, et al. Beneficial effects of herbal supplements in the treatment of
hepatitis C. Am J Gastroenterol. 2004;99:S68. [Abstract #208]
7. Lyons CD, Sterling RK, Stravitz RT, et al. Hepatitis C virus (HCV) in patients with hemophilia: safety of
outpatient percutaneous liver biopsy, spectrum of liver disease, and impact of human immunodeficiency
virus (HIV) coinfection. Am J Gastroenterol. 2004;99:S71. [Abstract #216]
8. Smith AD, Muir AJ, Heneghan MA, et al. What is the course of patients undergoing anti-viral therapy for
recurrent hepatitis C liver disease? Am J Gastroenterol. 2004;99:S85. [Abstract #259]
9. Mitchell S, Inverso N, Komar M, et al. Noninvasive measures are not predictive of nonalcoholic
steatohepatitis. Am J Gastroenterol. 2004;99:S99. [Abstract #305]
10. Shaheen NJ, Stuart E, Schmitz SM, et al. Pantoprazole reduces the size of post-banding ulcers after
elective endoscopic variceal band ligation: a randomized controlled trial. Am J Gastroenterol.
2004;99:S72. [Abstract #219]
11. Massoud OI, Zein N. Effect of transjugular intrahepatic portosystemic shunt on thrombocytopenia
associated with liver cirrhosis. Am J Gastroenterol. 2004;99:S98.[Abstract #304]
Article
Recent advances in herbal medicine for treatment of liver diseases.
http://www.ncbi.nlm.nih.gov/pubmed/21595500
Nilanjan Ghosh Rituparna Ghosh Vivekananda Mandal Subhash C Mandal
Dr. BC Roy College of Pharmacy and Allied Health Sciences, Durgapur, India.
Pharmaceutical Biology (Impact Factor: 1.21). 05/2011; 49(9):970-88. DOI: 10.3109/13880209.2011.558515
Source: PubMed
ABSTRACT Liver disease is a serious ailment and the scenario is worsened by the lack of precise therapeutic
regimens. Currently available therapies for liver ailments are not apposite and systemic toxicity inhibits their long
term use. Medicinal plants have been traditionally used for treating liver diseases since centuries as the toxicity
factor appears to be on the lower side.
Several phytochemials have been identified which have significant hepatoprotective activity with minimal systemic
adverse effects which could limit their long term use. The scenario calls for extensive investigations which can lead
to development of lead molecules for hepatoprotective molecules of future. This review deals with the biological
activity, mode of action and toxicity and forthcoming application of some of these leads.
These generally have strong antioxidative potential and cause induction of antioxidant enzymes like superoxide
dismutase, reduced glutathione and catalase. Additional mechanisms of hepatoprotection include stimulation of
heme oxygenase-1 activity, inhibition of nitric oxide production, hepatocyte apoptosis and nuclear factor-B
activation.
Out of the several leads obtained from plant sources as potential hepatoprotective agents, silymarin,
andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin
have been established as potent hepatoprotective agents. The hepatoprotective potential of several herbal
medicines has been clinically evaluated. Significant efficacy has been seen with silymarin, glycyrrhizin and Liv-52
in treatment of hepatitis, alcoholic liver disease and liver cirrhosis.
http://www.jtcm.org/article.asp?issn=2225-4110;year=2013;volume=3;issue=2;spage=88;epage=94;aulast=Xiao
REVIEW ARTICLE
Year : 2013 | Volume : 3 | Issue : 2 | Page : 88-94
Recent Advances in the Herbal Treatment of Non-Alcoholic Fatty Liver

Disease
Jia
1
Xiao1, Kwok
Fai
So2, Emily
Liong3, George
Tipoe4
Center for Gene and Cell Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen;
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
2
Department of Anatomy, Li Ka Shing Faculty of Medicine; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine; State
Key
Laboratory
of
Brain
and
Cognitive
Science,
The
University
of
Hong
Kong,
Hong
Kong
SAR,
China
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Department of Anatomy, Li Ka Shing Faculty of Medicine; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The
University of Hong Kong, Hong Kong SAR, China
Date of Web Publication
10-Apr-2013
Correspondence Address:
George L Tipoe
Department of Anatomy, Li Ka Shing Faculty of Medicine; Brain Hormone Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The
University of Hong Kong, Hong Kong SAR , China
DOI: 10.4103/2225-4110.110411
PMID: 24716162
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver injury across the
world. It is also strongly related to other pathological conditions, including obesity, diabetes, cardiovascular
diseases, and symptoms of metabolic syndrome. Pathogenesis of NAFLD remains not fully characterized
but is generally attributed to the occurrence of insulin resistance, lipid metabolism dysfunction,0 oxidative
stress, inflammation, and necro-apoptosis. Every potential therapeutic strategy should target one or some
of these pathological events in the liver. Over the past decades, application of herbal treatment for NAFLD
has received increasing attention due to its wide availability, low side effects, and proven therapeutic
mechanisms and benefits. In recent years, some monomers and certain functional mixtures of herbs have
been extensively examined for their potential uses in NAFLD treatment. In the present review, we selected
several herbal derivatives under intense basic and/or clinical investigations by carrying out a PubMed
search of English language articles relevant to herbal derivatives and NAFLD, such as polysaccharide
portion of wolfberry, garlic-derived monomers, red grape-derived resveratrol, and milk thistle-derived
substances. They have been shown to target the pathological events during NAFLD initiation and
progression both in pre-clinical studies and clinical trials. Although more detailed mechanistic researches
and long-term clinical evaluations are needed for their future applications, they offer unanticipated and
great health benefits without obvious adverse effects in NAFLD therapy.
Keywords: Garlic-derived monomers, Herbal treatment, Milk thistle-derived substances, Nonalcoholic fatty liver disease, Pathogenesis, Resveratrol, Wolfberry
CHINESE HERBAL MEDICINE FOR THE

TREATMENT OF HEPATITIS B INFECTION
by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon
http://www.itmonline.org/arts/hepb.htm
INTRODUCTION
Hepatitis B is endemic in Southeast Asia, estimated to infect up to 20% of the population in some
areas, such as the crowded subtropical city of Guangdong (Canton), China, with nearly as high
infection rates in other major urban areas of China. In a 1983 survey by the Hong Kong Medical and
Health Department, it was found that 10% of the local population are hepatitis B virus carriers.
Statistics compiled at the Third Teaching Hospital of Zhongshan Medical College (Guangzhou),
which specializes in the treatment of liver diseases, indicated about 15% of the local population in
1983 were hepatitis B carriers. Since techniques used at the time could not detect many cases, and
because the epidemic has been spreading, figures of 20% infection rates are reasonable estimates of
the situation in 1997.
Hepatitis B is responsible for considerable morbidity and mortality, contributing to the
incidence of liver cancer, the main cause of death in this area: 95% of liver cancer patients in
Southeast China test positive for hepatitis B virus. Infection by hepatitis B is a reason for denial of
exit visas from China. Further, the Chinese government has announced tentative plans to enforce
strict birth prevention measures for those who test positive for viral hepatitis, as part of a larger
program to reduce the number of births of children with various kinds of "defects." Hepatitis B is
also a major concern in other parts of the world, with its spread increasing to epidemic proportions
during the past two decades. The vaccine that is used to prevent infection has not been well-accepted
even by Western medical professionals who are at substantial risk of infection from their patients.
Nonetheless, today it has become common practice in the U.S. to inoculate newborns against
hepatitis B due to the high lifetime risk of infection.
Historical records indicate that a disease corresponding to hepatitis B was known to Chinese
doctors at least 1,800 years ago. At that time, the primary therapeutic measure was to prescribe a
combination of Chinese herbs, usually in the form of a decoction. The ingredients used in making
such decoctions-which include some herbs well-known in the West, such as rhubarb, licorice, and
cinnamon-have been a matter of record kept for all subsequent generations, so that today it is quite
easy to study the traditional Chinese medical theory and specific treatments for infectious hepatitis.
In ancient times, the appearance of jaundice was a primary indication of the disease, and relief of
jaundice would indicate that the therapeutic measures were effective. Today, jaundice is most
frequently associated with hepatitis A, an acute disease which, though often severe in symptoms, is
usually self-limiting. Hepatitis B, especially in the chronic cases and in well-nourished individuals,
rarely produces obvious jaundice. Therefore, other measures of the disease are relied upon to
monitor its progress and cure, such as serum levels of liver enzymes, antibodies to viral antigens,
viral antigens, and viral DNA.
Beginning around 1950, scientific evaluation of herb materials used for treatment of viral
hepatitis was undertaken in China and Japan, including isolation of active constituents, testing of
crude herb extracts and purified components in laboratory animals, and clinical studies of complex
formulas, individual herbs, isolated components, and synthetically-modified ingredients. Of the
more than 6,000 species of plants and animals used as sources of Chinese medicine, about 150 crude
materials have been identified as having measurable activity against viral hepatitis.
The actions of anti-hepatitis herbs may be subdivided, for purposes of discussion, into two
categories. One category is "hepatoprotective," including herbs and isolated compounds
demonstrated to protect laboratory animals from the toxic effects of carbon tetrachloride, a liver
poison that is frequently used to assay the ability of a substance to alleviate inflammation. Liver
protection can reduce the impact of viral hepatitis without necessarily reducing the viral load or the
immune response to the virus, though it appears that by using compounds with this property, the
activity of the virus is often reduced. This might occur by making it more difficult for chemical and
biochemical activators of the virus to affect cell surface receptors or to enter the infected liver cells;
the ability of the virus to infect new cells may also be impeded by these compounds. Liver
protection appears to be conferred by several processes including antioxidant activity, stimulating
bile production and release, and by inhibiting inflammation and fibrinogenesis. The other category is
"antiviral," indicating the ability to inhibit viral activity by promoting the production of interferon or
other immune responses to viruses (including both cell-mediated and antibody responses to infected
cells), or by blocking some step in viral replication, such as reverse transcriptase.
In clinical trials conducted in China during the past twenty years, reduction of serum liver
enzyme levels (ALT, AP) and seroconversion from HBsAG+ or HBeAG+ to negative are usually
used as modern standards of effectiveness, along with various measures of symptom reduction. As
revealed in this article, such tests have been used to demonstrate that a wide range of Chinese herbal
compounds are highly effective in the treatment of viral hepatitis; specific results vary because of
differing treatments and because of selection of differing populations for study. In some clinical
trials, up to 2/3 of patients show seroconversion, and clinical improvement to "normal" may be
attained for about 80% of the patients.
In Japan, medical doctors who prescribe Chinese herbs (up to 40% of all Western-trained
medical doctors in that country) report that a diagnosis of hepatitis is one of the principal reasons for
starting a patient on a course of Chinese herb therapy and that the Chinese herbs are more effective
than Western medicine for treating this disease.
An objection that may be raised by Western researchers regarding the published Chinese studies
is that the clinical reports may lack sufficient detail to reveal the true impact of the treatments. The
number of tests available for analyzing the results of therapeutic interventions has grown in recent
years, but not all such tests have been used in the Chinese research, perhaps because of budgetary
limitations. The formula described in this article was administered in China to patients who were
hospitalized for 12 weeks while taking the herb materials. Antigen tests for both HBsAg and
HBeAg, plus PCR evaluation of hepatitis viral DNA, were utilized to confirm the status of the
hepatitis infection before and after treatment. Results comparable to previously-published Chinese
trials were attained. This confirmation may help alleviate some of the concerns about results
reported in other trials, making it possible to further utilize the vast experience of Chinese
researchers in order to develop a satisfactory treatment for hepatitis B that is both economical and
easily applied.
PRINCIPAL HERBS/ACTIVE COMPONENTS FOR TREATING HEPATITIS B
Licorice and Its Component Glycyrrhizin
One of the substances frequently mentioned in the Chinese literature regarding hepatitis B is
glycyrrhizin, a component of licorice root (Glycyrrhiza uralensis is the species used in China).
Licorice was an ingredient in many of the prescriptions used in ancient times to treat hepatitis. The
root is well-known for its anti-inflammatory activity; the root, its crude extract, certain active
components, and synthetic derivatives of the active components are used in modern pharmacies for
the treatment of gastric ulcer. Glycyrrhizin zinc is useful topically as a treatment for skin
inflammation and ulceration. In Japan, recent in vitro studies indicate that glycyrrhizin sulfate may
be a useful compound for inhibiting HIV infection of cells, based on antiretroviral activity.
Glycyrrhizin ammoniate is a common flavoring agent used in the U.S., so the recognition that
glycyrrhizin is safe makes it attractive. Large doses of licorice or glycyrrhizin can, however, lead to
increased aldosterone production (by the adrenals) and imbalance of serum sodium and potassium
levels (both by affecting NaK-ATPase directly and via the action of aldosterone) in susceptible
individuals. This response is not common when glycyrrhizin is used in standard therapeutic amounts
for treatment of hepatitis; a typical dosage of glycyrrhizin corresponds to 15 grams per day of crude,
dried licorice. Licorice and its active components can be used in the treatment of Addison's disease
(characterized by reduced production of aldosterone and other corticosteroids). Glycyrrhizin is an
antioxidant and it promotes production of interleukin-2 (IL-2), two actions that help inhibit viral
diseases. Glycyrrhizin sulfate appears more active than ammoniate or other forms. Crude licorice
extract has the advantage of easy access, low cost, and a combination of several valuable active
components, but isolated glycyrrhizin is more readily absorbed than the glycyrrhizin in the total
herbal extract.
Schizandra and Its Component Schizandrin
Schizandrin, a lignan, is an active component of schizandra, the fruit from Schizandra sinensis.
Studies conducted in the 1970's in China revealed that schizandra and its component schizandrin
could strongly lower ALT and AP in animal models of hepatitis and in human patients. However, it
tended to have the problem that when administration of the compound ceased, there was a rebound
in these enzyme levels. Screening of various analogues led to the production of a new drug for
hepatitis known as DDB (dimethyl 1-4, 4'-dimethoxy-5,6,5', 6'dimethylene dioxybiphenyl 1-2, 2'dicarboxylate). This compound is strongly hepatoprotective, lowering ALS and AP, reducing alphafetal protein levels and bilirubin, and reducing liver lesions, as indicated by biopsy.
DDB, as a new drug, has undergone numerous trials in China, but is not an accepted drug in the
West. Schizandra extract has the advantage of being a safe food product of China that is also widely
used in the U.S. as an energy tonic and immune enhancing agent. In China, it is used in the
treatment of many ailments, including asthma, poor memory, severe fatigue, enteritis, and diabetes,
as well as for viral hepatitis. It enhances adrenal cortical function. In clinical tests of anicteric
infective hepatitis, just 3 grams per day of powdered schizandra fruit for one to three months led to a
clinical cure in 65% of cases. Higher doses, up to 15 grams per day, have been used in the treatment
of chronic hepatitis. It has been reported that schizandra, like its isolated lignans, has a quick action
and high rate of effectiveness for reducing plasma liver enzyme levels, but that relapse occurs
relatively easily. It has been suggested that schizandra be used with other herbs to increase the
therapeutic effect and prevent relapse.
Salvia and Its Components the Tanshinones
Salvia is perhaps the most frequently used herb in the modern practice of Chinese herbal medicine.
Salvia has been known to Chinese doctors for centuries, but had been used in only a few
applications, while today it is applied in the treatment of a wide range of diseases and symptoms.
Salvia has a complex chemistry, and as a result, the crude herb extract is often used rather than an
isolated component. The main active constituents are the tanshinones, a type of naphthaquinone.
Salvia is used in China as a health food product; regular ingestion is thought to prevent
cardiovascular diseases and other problems of aging.
Salvia plays two major roles in the treatment of liver disease. First, it has been learned that in
cases of severe or chronic liver disease, there are alterations in microcirculation (capillary bed
circulation) that appear to be part of the disease process. Patients treated with salvia who show
clinical improvements also show normalization of the microcirculation. Second, salvia inhibits
fibrinogen and aids in the resorption of fibrous plaques in the liver. It is thus widely used in the
treatment of liver cirrhosis. Salvia is provided as a single herb or in complex formulas in the
treatment of both acute and chronic hepatitis. As a single herb, it is given intravenously to quickly
improve the condition of patients suffering from liver or kidney diseases. Usual oral dosages of
salvia for treating severe diseases are 15-20 grams in decoction.
Hu-Chang and Its Anthraquinone Components
Hu-chang (Polygonum cuspidatum) refers to one of the many species of Polygonum used by
Chinese doctors. It contains anthraquinones as main active components, as well as resveratrol, a
stilbene. The herb, used alone, or in combination with other herbs, has been reported to cure both
acute and chronic hepatitis, though it has been suggested to have greater impact on acute hepatitis.
Hu-chang is one of the broad-spectrum antiviral agents under investigation in China and Japan. Huchang prevents lipid peroxidation, and thus prevents hepatic degeneration; it also promotes liver cell
regeneration through RNA synthesis. The herb has been used in China to rescue patients with severe
viral hepatitis who do not seem to recover when given standard Western therapies. In addition, huchang influences microcirculation in a manner similar to salvia.
Curcuma and Its Essential Oil Components
Curcuma (yujin) refers to one of three major species of curcuma used in Chinese medicine, the other
two are turmeric (huangjiang) and zedoaria (ezhu). It contains a complex essential oil that regulates
blood lipids and treats infectious hepatitis. In a study of acute and chronic hepatitis involving 33
patients, all but one responded to the daily ingestion of a powder of curcuma (5 grams each time,
three times daily), with 2/3 of the patients having subjective symptoms completely relieved.
Curcuma stimulates bile secretion. Curcumin, a bright yellow complex ketone found in both
turmeric and curcuma, is currently under investigation as an anti-HIV agent; it appears to block a
long terminal repeat (LTR) during reproduction of the virus. This action may apply to other viruses
and to preventing activation of cancer genes. Curcumin is also a powerful anti-inflammatory agent.
Ligustrum and Its Component Oleanolic Acid
Ligustrum refers to the seed of Ligustrum lucidum. It is rich in oleanolic acid, a compound that
appears to be effective in treatment of liver diseases, acting mainly as a liver-protective agent. It is
reported to be efficacious in treating both acute and chronic hepatitis, with a cure rate of 70% for
acute hepatitis and it was markedly effective in treating 44% of cases of chronic hepatitis. Ligustrum
has been identified as one of the herbs that strongly enhances immune responses, reversing
leukopenia from cancer therapeutic agents. Ligustrum is used as a health food in the U.S. to enhance
immune functions.
Silybum and Its Component Silymarin
Silymarin is a complex flavonoid from Silybum marianum, an herb that was initially introduced as a
therapeutic agent by European researchers, but soon taken up by their counterparts in China as a
treatment for liver diseases. Its main action is to protect the liver from damage, and it is used, for
example, in the early stage of liver destruction due to ingestion of poisonous mushrooms, to save the
lives of victims. A concentrated extract of silybum, rich in silymarin, is sold as a health product in
the U.S. and the isolate has been sold as a drug in Europe ("Legalon") for the treatment of liver
disease for the past 15 years. A dosage of 140 mg/day is reported to be liver protective and a dosage
of 420 mg/day is reported to help repair liver damage. It is not clear that silymarin can cure viral
hepatitis. Silybum extracts are widely sold as health foods in the United States.
A PROTOCOL FOR TREATMENT
The following formula is recommended for treatment of hepatitis B and was the subject of a clinical
trial conducted in China during 1994-1996, and later produced as a tablet for use in Western
countries (Seven Forests Salvia/Ligustrum Tablets):
Salvia (danshen, root of Salvia miltiorrhiza): 21%
Licorice (gancao, root of Glycyrrhiza uralensis): 16%
Hu-chang: (huzhang, rhizome of Polygonum cuspidatum): 16%
Curcuma (yujin, tuber of Curcuma longa): 11%
Schizandra (wuweizi, fruit of Schizandra sinensis): 10%
Ligustrum (nzhenzi, fruit of Ligustrum lucidium): 16%
Atractylodes (baizhu, rhizome of Atractylodes macrocephala): 11%
[total is 101% due to rounding]
Atractylodes is included in this formulation as a digestive aid, though its use can also be justified on
the basis of laboratory studies showing that it protects mice from liver injury induced by carbon
tetrachloride and promotes liver cell regeneration; it is also used as an ingredient in several complex
formulas for treatment of viral hepatitis.
The herb ingredients are made as a decoction, dried, and formed into tablets of 800 mg each
(880 mg in the Chinese clinical trial). The dosage schedule for the herb materials is 9 tablets each
time, three times daily, for a total dose of 27 tablets or about 23 grams of herb extracts. This
corresponds, approximately, to 94 grams of crude herb materials used to prepare a decoction, after
which the decoction is dried [the herb extract was manufactured by Sun Ten Laboratories, Irvine,
California]. The daily dosage of licorice, which is the marker compound for determining dosage of
the mixture to administer, is 15 grams.
A vitamin tablet was used simultaneously, one tablet each time, three times daily in the Chinese
trial. Each tablet contained:
Silybum extract (8:1): 135 mg

Vitamin C (as calcium ascorbate): 250 mg
Beta carotene: 6 mg (10,000 IU)
Vitamin E: 133 IU
Zinc (acetate): 5 mg
Selenium (amino acid chelate): 40 mcg
Quercetin: 100 mg
l-Cysteine: 40 mg
Vitamin B1: 5 mg
Vitamin B2: 3 mg
Vitamin B3: 10 mg
Vitamin B5: 10 mg
Vitamin B6: 12 mg
Vitamin B12: 50 mcg
Folic acid: 200 mcg
In the U.S., this tablet is replaced by two formulas (produced by ITM, White Tiger label):
Quercenol, an antioxidant mixture that includes silybum, and Calmagnium, a mineral/vitamin
mixture. In addition, some protocols include Alpha-Curcumone (a source of alpha-lipoic acid, an
antioxidant used in the treatment of hepatitis). At standard recommended dosage, these supplements
provide a larger amount and wider range of nutrients and antioxidants that were applied in the
Chinese trial.
DURATION OF TREATMENT
Based on clinical experience in China, a 12-week treatment period is satisfactory as a standard

course of treatment for chronic hepatitis B, which can be repeated once more if necessary. The basis
for recommending this treatment period is a compromise between maximizing compliance and
assuring measurable activity of the prescribed compounds. For the purpose of assuring maximum
compliance, the treatment duration should be as short as possible. The minimum duration of
treatment depends on the amount of time that is reasonable to obtain a satisfactory therapeutic
effect, which is defined for the purpose of the Chinese study as the ability to attain 50% of patients
experiencing both seroconversion (of HBsAg and/or HBeAg), and a decline of ALT and AP to
within 1.5 times the maximal level of the normal range. For the other 50% (or fewer) of the patients,
a second course of treatment is recommended. A certain number of non-responders is to be
expected, even with two courses of treatment.
A problem with long-term follow-up in the case of hepatitis B is that reinfection is always
possible, especially since the disease can be sexually transmitted and the individual's partner may
not have been treated at the same time. On the other hand, it is possible that the primed immune
system of the successfully treated patient can prevent reinfection. According to Chinese reports,
reversion to positive antigen test response occurs in only about 10% of patients successfully treated
with Chinese herbs if followed-up during the first year after conclusion of herb therapy. This
apparent conversion to positive hepatitis test is probably the result of activation of remaining latent
virus in most cases.
SAMPLE STUDIES
Following are brief reviews of eight clinical trials in which a treatment time of three months or less
was sufficient to obtain results such as those suggested above. The numbers in brackets after the
study summary are the reference codes for the report abstract as found in the journal Abstracts of
Chinese Medicine.
1. Study reported in 1989 of treatment of chronic active hepatitis B.
The treatment protocol included a decoction, a tableted herb
component, and vitamin E, used daily for three months. The control
group used biphenyldicarboxylate (in place of herb decoction), plus
the herb tablet and vitamin E. The seroconversion rate of HBsAg for
those taking the herb decoction was 67%, while that for the control
was just 7%; for HBeAg, the rates were 53% and 13% respectively. In
a one year follow-up of 20 cases from each group, the relapse rates
were 10% and 60% respectively. According to this study, a three
month treatment time was adequate to obtain a 50% seroconversion
rate. [891191]
2. Study reported in 1989 of asymptomatic carriers with positive
HBsAg treated with a decoction given twice daily for one month as a
treatment course. If the HBsAg test became negative, the decoction
was administered only every other day for one or more additional
months, but if it remained positive, an additional herb was added
and the treatment continued daily. When the test was negative twice
consecutively, the treatment was discontinued. 58 of 80 cases
(73%) were cured within three courses of therapy and 17 others had
reduced HBsAg titers. This study shows that three months of therapy
is adequate to obtain at least 50% seroconversion. [891152]
3. Study reported in 1991 included 304 patients with chronic hepatitis
B. They were treated with herbs in pill form for 2 to 3 months. 128 of
the patients, 63%, were rated cured, with HBsAg and HBeAg
becoming negative. Only 32 patients failed to respond. This study
shows that a three month treatment period is adequate for at least
50% seroconversion. [930249]
4. Study reported in 1982 involving 80 patients with chronic or acute

hepatitis. Glycyrrhizin was administered along with vitamins to the
treatment group and the vitamins were given with injection of
inosine in the control group. Treatment time was one month for
acute hepatitis and three months for chronic hepatitis. Clinical cure
was claimed for 85% of the acute hepatitis group and 75% of the
chronic hepatitis group treated with herbs. Only a few of the patients
treated here were positive for HBsAg and HBeAg. Of those who were
positive, there was no seroconversion in the control group, but
seroconversion occurred in about 50% of the glycyrrhizin treated
group. Most of the seropositives at the beginning of the trial were in
the chronic hepatitis group. This study indicates that 50%
seroconversion can be achieved in a three month period of
treatment. [Reported in the English language Journal of Traditional
Chinese Medicine 1982; 4(2): 127-132]
5. A study reported in 1987 with 104 patients having hepatitis A and
72 having hepatitis B, all acute cases, were treated with a decoction
plus vitamin B complex, vitamin C, and diisoproplylamine ascorbate.
It was claimed that 158 cases (90%) were cured in 6 to 24 days,
average duration of treatment was 16 days. Seroconversion
information was not provided. This is consistent with the practice of
treating acute hepatitis (A or B) for only about one month. In some
other studies of acute hepatitis, a course of treatment was 15 days
and might be repeated once. [880291]
6. A study reported in 1987, with 71 cases of hepatitis B with positive
HBsAg, were treated with a decoction of herbs. Acute cases were
given 3-4 doses per day for 20 days as a therapeutic course. Other
cases were given just 2 doses per day for 30 days as a therapeutic
course. When HBsAg became negative, the treatment was reduced
to once every other day for one month. A control group received
Western drugs and, if SGPT was elevated, an herb syrup known to
control that condition was given. 47 cases in the treatment group
(67%) seroconverted. The exact number of therapeutic courses was
not reported in the abstract, but presumably was one to three
courses, as standard practice. [880263]
7. In a study reported in 1987, a treatment for hepatitis B in decoction
form was given to 31 patients. The effect of this therapy, based on
tonic herbs, was not especially great, but it was reported that it took
"at least two months" to attain seroconversion. A three month trial
with a more effective therapy would therefore appear adequate.
[880251]
According to this information, among the participants who respond to the therapy, those with
acute hepatitis should be cured (or improved) within about two months and those with chronic
hepatitis should be cured (or improved) within three months.
POSSIBLE ADVERSE REACTIONS
There are some potential adverse reactions to any herb therapy, as follows:
a) gastro-intestinal reactions including nausea, bloating, flatulence, diarrhea, constipation, vomiting.
b) allergy type reaction, including hepatic reaction.
The above reactions are idiosyncratic, that is, they cannot be predicted in advance and do not
represent inherent properties of the selected herbs. If such reactions occur, it may be necessary to
have the individual experiencing the reaction discontinue the treatment. The gastro-intestinal
reactions usually subside within three to five days and thus they should be tolerated for that long
before discontinuing unless they are severe. Allergy-type reactions are not expected to resolve with
longer use of the herbs.
There are some possible specific reactions to the therapies. Licorice may cause excessive
aldosterone production, with symptoms of edema, fatigue, and arrhythmia. The dosage of licorice in
this protocol is set at a level for which this reaction is rare. Hu-chang, which contains
anthraquinones, ligustrum, which contains oils, and curcuma, which increases bile flow, may induce
intestinal peristalsis, loose stool, or diarrhea. In most individuals, this response will resolve with
continued use of the herbs. However, in rare instances, the problem might persist.
In the Chinese clinical trial of the herb formulation described here and in three years experience
in the U.S. with the same preparation, adverse reactions to the herb/nutrient treatment have not been
observed.
In the event that such responses are noted and believed to be due to the herb therapy (as
opposed to due to the hepatitis), the herb therapy should be discontinued for two consecutive days,
to determine whether or not the observed problems are due to the ingestion of the herbs (for liver
hypersensitivity reaction, the duration of symptom persistence could be longer). None of the herbs
are inherently toxic in the dosage range recommended.
TRADITIONAL CHINESE MEDICAL DESCRIPTION OF THE HERB THERAPY
Hepatitis begins as an acute disease (with manifestations of heat), which is described in Chinese
medical terminology as a toxic heat syndrome. As the disease develops, it is said to manifest
symptoms of accumulated dampness and liver qi stagnation. In the event that the disease becomes
chronic, it is believed that the yin becomes deficient, there is blood stasis (mainly affecting the
liver), and the qi is weakened (weakness of qi may be the cause of the acute disease becoming a
chronic disease).
Hu-chang is the herb that has been selected to treat the toxic heat syndrome. It is described as a
cold, bitter, mildly pungent, and sour agent that clears up heat, detoxifies, invigorates blood, and
disperses swelling. Antibacterial and antiviral effects have been demonstrated in pharmacology
experiments with this herb.
Curcuma is the herb that has been selected to treat the stagnant qi that develops. The herb is said
to have a cool property, with a bitter and pungent flavor. It is traditionally used to regulate the flow
of qi, resolve qi stagnation, disperse stagnant blood, and control pain. It is applied to treatment of
liver pain and jaundice. Modern research shows that it stimulates gastric secretion and bile secretion,
to improve appetite and improve digestion.
Salvia is the herb that has been selected to treat blood stasis. It is described as having a mild
cold property and bitter flavor. It is traditionally used to invigorate blood circulation, cool the blood,
nourish the blood, and calm mental irritability. Modern research shows that it rectifies abnormal
patterns of capillary bed circulation and successfully treats viral hepatitis when used in relatively
large dosage.
Ligustrum is the herb that has been selected to treat yin deficiency. It is described as having a
neutral property and bitter taste. It is traditionally used for yin deficiency, internal heat, weakness of
the lower back and legs, and insomnia. Recent studies indicate that it enhances immune functions
and protects liver cells from damage.
Licorice has been selected as the qi tonic herb. It is described as having a neutral property and
sweet flavor. It is traditionally used to supplement the spleen, replenish qi, clear heat, remove toxin,
and harmonize the stomach. It has been applied in the treatment of toxic swellings, diarrhea, thirst,
cough, and palpitation. Recent studies show that it has anti-inflammatory action similar to that of the
corticosteroids.
Atractylodes has been selected as the herb to remove dampness. It is also a qi tonic herb. It is
described as having a warm property, sweet, mildly bitter and aromatic flavor. Traditionally, it is
used to supplement the spleen, tonify qi, dry dampness, deliver water, harmonize the stomach and
spleen. It has been used for treatment of fatigue, loss of appetite, diarrhea, edema, spontaneous
sweating, vomiting, and dizziness. Modern research shows that it promotes immune system
functions, protects the liver from chemical injury, and has anticoagulant properties.
Schizandra has been selected as an aid to the qi tonic (licorice) and the yin nourishing herb
(ligustrum). It is traditionally described as having a warm property and sour flavor. It is used to
nourish the kidneys, astringe the lungs, control diarrhea, and promote secretion of fluids (e.g.,
saliva). At higher dosage, it is said to reinforce the qi and nourish the yin. It has been applied to the
treatment of fatigue, insomnia, amnesia, thirst, spontaneous sweating, cough, and thirst. Modern
research shows that schizandra enhances adrenocortical function, promotes bile secretion, and
reduces liver enzyme levels.
The complex formula has the properties of tonifying and regulating qi, of nourishing and
astringing yin, of vitalizing blood, clearing heat and toxin, and drying dampness. Its quality is
cooling, its taste is mainly sweet and bitter, with some sour and acrid (pungent) properties.
HERB DOSAGES
Chinese doctors recommend herbal dosages that have been recorded in the classical and modern
Materia Medica publications. Modern clinical trials confirm the validity of these dosage
suggestions. Generally speaking, when making a complex formula, the dosage of most ingredients is
lower than would be utilized if the herb was selected as a sole ingredient, due to the expectation of
synergistic action (attaining the same goal through complementary pathways). Because of the
relatively short duration of treatment in this study, the dosage of each item has been selected at a
relatively high level within the range that is usually recommended.
Hu-chang is recommended to be used in the dosage range 9-30 grams/day. A daily dosage of 15
grams has been selected for this treatment. In higher dosage, the herb can cause dry mouth, bitter
after taste, nausea, vomiting, abdominal pain, and diarrhea.
Curcuma is usually recommended in the dosage range 4.5-9 grams/day. However, in a published
trial for treatment of hepatitis, it was used in a dosage (as powder) of 15 grams/day. A daily dosage
of 10 grams per day has been selected for this treatment. In higher dosage, this herb may cause
abdominal aching and diarrhea.
Salvia is recommended in the dosage of 6-15 grams for typical uses, but 15-30 grams to treat
severe diseases, and up to 30-60 grams for severe blood stasis syndrome. The extract has been used
intravenously in doses of 22.5 grams or higher (raw material equivalent) for treatment of hepatitis. A
daily dosage of 20 gramshas been selected for this treatment. Higher dosage may cause dry mouth,
dizziness, lassitude, numb sensation of limbs, shortness of breath, nausea, vomiting, and
gastrointestinal disturbance; these responses tend to subside of themselves without suspending
treatment.
Ligustrum is recommended in dosages of 6-15 grams per day. Doses of up to 50 grams per day
(made as fluid extract) have been used successfully to treat bronchitis. A daily dosage of 15
grams has been selected for this treatment. Higher dosage may cause bloating and diarrhea.
Licorice is recommended to be used in doses of 3-6 grams per day. Doses up to 18 grams per
day have been used in treatment of tuberculosis. 7.5-15 grams per day have been used to treat
gastric and duodenal ulcers. A daily dose of 15 grams has been selected for this treatment.
Excessive dosage or long-term use of moderate dosage can cause an adverse reaction in up to 20%
of patients, including possible symptoms of edema, weak limbs, spastic numbness, dizziness,
headache, hypertension, hypokalamia.
Atractylodes is recommended in the dosage range of 3-12 grams. Doses up to 60 grams per day
have been used for short-term applications. A daily dose of10 grams has been selected for this
treatment. Adverse reactions to large dosage have not been described, but gastro-intestinal responses
might be expected.
Schizandra is recommended in the dosage range of 1.5-9 grams per day; with 6-9 grams per day
recommended to reinforce qi and nourish yin. Up to 15 grams per day (powdered herb) have been
used in the treatment of hepatitis. A daily dosage of 9 grams has been selected for this treatment.
Higher dosage may cause heartburn, acid indigestion, stomach ache and anorexia.
The total dosage of the seven herbs is 94 grams. In a review of hepatitis formulas listed in
modern Chinese books (at the ITM library), formulation characteristics were as follows: except for
the one formula used temporarily at very high dosage, the formula size and dosage range is
reasonably consistent at 9-12 herbs and 100-140 grams, typically 11-14 grams of each herb. In the
formulation described in this article, the number of herbs is only 7, and the total dosage is just 94
grams (average, about 13 grams each). This reduction in number of ingredients-compared to that
used in several recent trials with complex formulas-has been purposefully chosen to simplify the
treatment protocol. A few clinical trials rely on one to three herbs. The relatively lower total dosage
was deemed likely to be effective as the higher dosage treatments because of the careful selection of
ingredients (focused formula design). It should be noted that there is an additional herb extract
present in the "vitamin tablet," namely silybum, thus raising the total number of herbs to 8 (the
substitute item, Quercenol, contains other herb extracts, including those from green tea, sophora,
and grape seed); the dosage of herbs is therefore slightly increased by the inclusion of the vitamin
tablet. The additional vitamins and minerals may provide an action in the current protocol that
would otherwise have been obtained from herb ingredients.
RESULTS OF ONE CHINESE CLINICAL TRIAL
In a clinical trial carried out at three test sites in China, there were 94 inpatients treated and
evaluated, utilizing three therapies (at each site). The main test therapy was the formula now called
Salvia/Ligustrum Tablets, taken with the vitamin tablet. The primary control therapy was a tablet of
the same size and same dosage made with lentinus extract (shiitake mushroom, used in Japanese
treatment of hepatitis B), atractylodes, and schizandra; the control patients also took the vitamin
supplement. The third control group took a patent medicine made in China that was understood, by
the Chinese researchers, to be the most effective one available.
As a result of 12 weeks treatment, in the Salvia/Ligustrum group and the Lentinus group there
was marked improvement in symptoms and liver enzymes, more so than with the Chinese patent
remedy. Antigen conversion from positive to negative occurred for HBeAg in 2/3 of patients treated
by Salvia/Ligustrum or Lentinus Tablets, but in only 1/3 of those receiving the Chinese patent.
HBsAg conversion occurred only in a few patients, 2 receiving Salvia/Ligustrum, 1 receiving
Lentinus, and none receiving the Chinese patent. Nearly half (9/20) of those tested showed viral
DNA conversion from positive to negative in those receiving Salvia/Ligustrum, and in one-third
(7/21) of those receiving Lentinus, but only in about one-fourth (6/26) of those receiving the
Chinese patent.
In sum, the Salvia/Ligustrum formula (used with a nutritional supplement) produced excellent
results in treating hepatitis B patients. There were also obvious benefits, though less dramatic, for
treatment with lentinus, schizandra, atractylodes, and the nutritional supplement. These treatments
were superior to one that had been deemed the best available in China by the researchers. The study
was conducted at the Hepo Medical Technical Research Institute in Beijing, the Haixia Hospital in
Quanzhou (Fujian Province), and the Henan Medical Science Institute. Testing equipment and
reagents were provided by the Tumor Virology Department of the Centers for Disease Control,
Atlanta.
The original study design called for treatment of 200 patients. New government regulations in
China require data on safety (such as laboratory animal tests) in order to carry out clinical trials,
unless the herbs are in the form of decoction. This regulation halted (perhaps temporarily)
continuation of the trial despite the fact that no significant adverse events were noted for any of the
participants enrolled thus far.
REFERENCE SOURCES
The Chinese Medicinal Materials Research Centre at the Chinese University of Hong Kong (in
Shatin) produced three resources which provided most of the background information about active
constituents, pharmacology, and clinical trials used in this article:
The two volume book Pharmacology and Application of Chinese
Materia Medica, edited by Chang and But, published by World
Scientific (Singapore), copyright 1986.
The proceedings of a meeting that took place in 1983, Advances in
Chinese Medicinal Materials Research, edited by Chang, et al.,
published by World Scientific (Singapore), copyright 1985. The
meeting had a section on liver diseases for which seven papers were
presented in the proceedings.
The quarterly journal of English language abstracts of Chinese
medical journal articles, Abstracts of Chinese Medicine, published
continuously since 1986; the 1988 issue (vol. 2. #1) included the
review by Han Dewu, et al.: "Chinese medicines for the prevention
and treatment of viral hepatitis."
Additional information was obtained from the following English language sources:
Recent Advances in Chinese Herbal Drugs, Science Press, Beijing, 1991.
The Illustrated Chinese Materia Medica, by Yen, SMC Publishing, Taipei,
1992.
Oriental Materia Medica by Hsu and Hsu, Oriental Healing Arts Institute,
Long Beach, CA 1980.
Modern Study and Application of Materia Medica by Dong and Yu, China
Ocean Press, Beijing, 1990.
Journal of Traditional Chinese Medicine [English], Beijing, published
continuously since 1981.
A news article in Beijing Xinhua [English version], December 20, 1993, and reported again in
New York Times, Feb. 27, 1994, described plans for eugenics policies in China that included
hepatitis B infection. An article, "A historical study of Chinese drugs for the treatment of jaundice,"
by Saburo Miyasita in American Journal of Chinese Medicine, (4(3), 239; 1976), provides
background information on herbs mentioned in early Chinese literature. Formulation of the vitamin
supplement was based, in part, on information obtained from: Nutritional Influences on Illness, by
Werbach, Third Line Press, Los Angeles, 1993.
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