DrugRes/2016-05-1190/22.6.
2016/MPS
Adjunctive Therapy with Curcumin for Peptic Ulcer: a
Randomized Controlled Trial
Authors A. Khonche1, O. Biglarian1, Y. Panahi2, G. Valizadegan1, S. S. Soflaei3, M. E. Ghamarchehreh1, M. Majeed4,
Affiliations Affiliation addresses are listed at the end of the article
Key words
●
▶ peptic ulcer
●
▶ dyspepsia
●
▶ helicobacter pylori
●
▶ curcumin
●
▶ randomized controlled trial
received 03.05.2016
accepted 27.05.2016
Bibliography
DOI http://dx.doi.org/
10.1055/s-0042-109394
Published online: 2016
Drug Res
© Georg Thieme Verlag KG
Stuttgart · New York
ISSN 2194-9379
Correspondence
Y. Panahi, PhD
Chemical Injuries Research
Center
Baqiyatallah University of
Medical Sciences
Molla-Sadra Street
Tehran, P.O. Box: 19945-581
Iran
Tel.:  + 98/218/8211 524
Fax:  + 98/218/8211 524
yunespanahi@yahoo.com
A. Sahebkar, PharmD, PhD
Department of Medical
Biotechnology
School of Medicine, Mashhad
University of Medical Sciences
Vakilabad blvd.
Mashhad, Iran,
P.O. Box: 91779-48564
Iran
Tel.:  + 98/513/8002 288
Fax:  + 98/513/8002 287
sahebkara@mums.ac.ir
A. Sahebkar5, 6
Abstract
▼ breath test (UBT) at 4 weeks following the end of
Background:  Curcumin, the bioactive ingredi-
ent of turmeric, has been shown to improve the
treatment of peptic ulcer (PU) in animal studies.
However, clinical studies confirming this effect
of curcumin have been scant.
Objective:  To assess the efficacy of adjunctive
therapy with curcumin on the eradication of
Helicobacter pylori infection and severity of dys-
pepsia in patients with PU.
Methods:  In this randomized double-blind
placebo-controlled parallel-group trial, patients
diagnosed with PU were assigned to standard H.
pylori eradication triple therapy with clarithro-
mycin (500 mg b.i.d.), amoxicillin (1 000 mg b.i.d.)
and pantoprazole (40 mg b.i.d.), and randomized
to receive either curcumin (500 mg/day) or pla-
cebo as adjunct to standard treatment. Severity
of dyspepsia symptoms was evaluated using the
Hong Kong dyspepsia index (HKDI). Eradication
Introduction
▼ antibiotics and a proton pump inhibitor (PPI) for
Peptic ulcer (PU) is a common disease that
involves stomach and first part of small intestine
causing defects in gastrointestinal mucosa. The
global prevalence of PU is more than 4 % [1].
Around 10 % of the world population has been
estimated to experience gastric or duodenal
ulcer in their life time [2]. Helicobacter pylori is
the main pathologic cause of PU [3] and is one of
the most important causes of gastric cancer [4].
Around 65–95 % of gastric and 50–75 % of duode-
nal ulcers are causally related to H. pylori infec-
tion [5]. Upper abdominal pain, abdominal
fullness, gastroesophageal reflux and nausea are
the most common symptoms of PU, and are
jointly known as dyspepsia. PU might be compli-
cated by upper abdominal bleeding and gastric
or duodenal perforation [1]. Standard treatment
Original Article
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
of H. pylori infection was assessed using the urea
treatment.
Results:  Adjunctive therapy with curcumin
was associated with a greater improvement of
dyspepsia symptoms according to the HKDI score
(change score:  − 12.90 ± 2.81 vs.  − 9.60 ± 3.39 in
the curcumin and control group, respectively;
p < 0.001). The number of subjects whose dys-
pepsia was resolved during the course of treat-
ment was significantly higher in the curcumin
(27.6 %) vs. placebo (6.7 %) group (p = 0.042). Nev-
ertheless, the results of UBT test showed equal
rate (73.3 %) of H. pylori eradication in the study
groups. Curcumin was safe during the course of
trial.
Conclusion:  Addition of curcumin on top of the
standard anti-helicobacter regimen in patients
with PU is safe and improves dyspepsia symp-
toms but has no enhancing effect on the eradica-
tion of H. pylori infection.
for H. pylori-positive PU is triple therapy with 2
14 days; however, the eradication of H. pylori is
still a challenge. The maximal eradication rate of
the standard regimen is 85 % and more than 15 %
of H. pylori-positive patients must shift to bis-
muth-containing quadruple therapy for 2 weeks
[6].
Curcumin is a yellow polyphenolic pigment
obtained from turmeric rhizome. It is a nutraceu-
tical with documented safety and numerous
pharmacological effects such as antioxidant,
antimicrobial, anti-fungal, anti-inflammatory,
anti-angiogenic and pro-apoptotic properties
[7, 8]. Several lines of evidence have indicated the
efficacy of curcumin supplementation against
several human diseases such as anxiety and
depression [9, 10], osteoarthritis [11, 12], meta-
bolic syndrome [13], dyslipidemia [14–16], non-
Khonche A et al. Curcumin for Peptic Ulcer …  Drug Res
 Original Article
alcoholic fatty liver disease [17, 18], atherosclerosis [19, 20],
chronic complications due to sulfur mustard intoxication [21–
24], solid tumors [25], colorectal cancer [26] and inflammation
[27, 28].
Several in vitro and animal studies have revealed the inhibitory
effect of curcumin on H. pylori [29–37], however clinical studies
evaluating the efficacy of curcumin supplementation in PU have
been scarce. To the best of our knowledge, only 2 previous clini-
cal studies were available. In an uncontrolled clinical one, treat-
ment with 3 non-antibiotics plus curcumin could eradicate H.
pylori only in 12 % of patients, though the reduction in PU symp-
toms with curcumin was significant [38]. The second study com-
pared the efficacy of standard triple therapy and curcumin in H.
pylori-positive patients. The results revealed that curcumin
could not eradicate H. pylori infection but could ameliorate pep-
tic ulcer symptoms [39]. However, no study has yet assessed the
value of adding curcumin as an adjunct to standard anti-helico-
bacter regimen in the context of a randomized controlled trial.
Here, we designed a randomized double-blind placebo-con-
trolled clinical trial to investigate the effect of adjunctive ther-
apy with curcumin on dyspepsia symptoms and eradication of
H. pylori in patients diagnosed with PU.
Methods and Subjects
▼ sion 20 (IBM Corp., Armonk, NY, USA Inc.). Data were expressed
Subjects
This study was designed as a randomized double-blind placebo-
controlled clinical trial. Participants were selected from patients
(age range: 20–50 years) referring to the gastrointestinal endo­
scopy unit of the Baqiyatallah Hospital (Tehran, Iran) with gas-
tric pain and symptoms of dyspepsia. Inclusion criteria were
diagnosis of clean-based gastric or duodenal ulcers in gastros-
copy and presence of H. pylori infection based on the rapid ure-
ase test on the biopsy specimens of antral mucosa. Exclusion
criteria were history of receiving anti-helicobacter treatment,
concomitant treatment with corticosteroids, chronic diseases,
malignancies including gastric malignancy, and lack of adher-
ence to the study protocol defined as non-compliance with the
administered anti-helicobacter triple therapy, or changing the
triple therapy regimen. 4 weeks following the end of treatment,
urea breath test (UBT) with C14 was performed to evaluate erad-
ication of H. pylori infection. UBT test was performed in a radio-
isotope laboratory with blinded staff to the study design and
assigned interventions. The study protocol was approved by the
Ethics committee of the Baqiyatallah University of Medical Sci-
ences and written informed consent was obtained from the par-
ticipants prior to the enrollment. The trial was registered at the
UMIN Clinical Trial Rergistry (http://www.umin.ac.jp/ctr/ with
the unique identification code of R000025483 UMIN000022106.
Study design
This study was a randomized double-blind placebo-controlled
trial with a parallel-group design. Eligible patients were assigned
to standard H. pylori eradication triple therapy with clarithro-
mycin (500 mg b.i.d.), amoxicillin (1 000 mg b.i.d.) and pantopra-
zole (40 mg b.i.d.), and randomized to receive either curcumin
(Curcumin C3 Complex®, Sami Labs LTD, Bangalore, India;
500 mg/day) or placebo as adjunct to standard treatment. In
order to improve the bioavailability of curcumin, 5 mg piperine
(Bioperine®; Sami Labs LTD, Bangalore, India) was added to each
500 mg curcumin capsule [40, 41]. Placebo capsules contained
Khonche A et al. Curcumin for Peptic Ulcer…  Drug Res
DrugRes/2016-05-1190/22.6.2016/MPS
microcrystalline cellulose plus equal amount (5 mg) of piperine.
C3 Complex® preparation that was used in the present study
contained 3 major curcuminoids including curcumin, demeth-
oxycurcumin and bisdemethoxycurcumin in a patented ratio.
The purity of the product for the 3 major curcuminoids was
determined using HPLC (supplementary files 1 and 2). Curcumin
and placebo capsules were matched in color, shape and size.
Assessment of symptoms
Severity of dyspepsia symptoms was evaluated using the Hong
Kong dyspepsia index (HKDI). HKDI consists of 12 items: stom-
ach pain, upper abdominal bloating, upper abdominal dull ache,
stomach pain before meals, stomach pain when anxious, vomit-
ing, nausea, belching, acid regurgitation, heartburn, feel of acid-
ity in stomach and loss of appetite). Each item was graded on a
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Likert scale with scores of 1 (asymptomatic), 2 (mild symptoms
that can be easily ignored), 3 (awareness of symptoms but easily
tolerated), 4 (severe symptoms sufficient to cause interference
with normal daily activities) and 5 (incapacitating symptoms
causing inability to perform daily activities and/or require days
off work). A cut off score of  ≥ 16 was used to categorize patients
as dyspeptic and non-dyspeptic [42].
Statistical analysis
Statistical analyses were performed using the SPSS software ver-
as mean ± SD or number ( %). Within-and between-group com-
parisons were performed using Wilcoxon signed-ranks test and
Mann-Whitney U test (for normally distributed data), respec-
tively. Categorical variables were compared using Fisher’s Exact
test. In all comparisons, a p-value of  < 0.05 was considered as
statistically significant.
Results
▼
From the initial 68 subjects who entered the study, 60 subjects
(30 in each group) completed the study. 8 patients were lost to
follow-up and did not refer to the study center for a final visit
and UBT ( ●▶  Fig. 1).
The study groups were comparable in age, gender, anthropo-
metric indices (weight, height and body mass index) and fre-
quency of smoking habit ( ● ▶  Table 1). The results of UBT test
showed equal rate of H. pylori eradication in the study groups. In
both groups, 22 out of the 30 subjects (equivalent to 73.3 % of
subjects) had their infection eradicated. Individual analysis of 12
items in the HKDI questionnaire revealed significant improve-
ment of all dyspepsia symptoms, except vomiting, in both cur-
cumin and placebo groups. Consistently, total HKDI score was
found to be improved in both curcumin and placebo groups
(p < 0.001). Nevertheless, comparison of the magnitude of
changes revealed greater improvements in upper abdominal
dull ache (p = 0.002), stomach pain before meals (pp = 0.004),
belching (p = 0.028) and total HKDI score (p < 0.001) in the cur-
cumin vs. placebo group ( ● ▶  Table 2).
At baseline, all subjects in the curcumin and placebo groups had
HKDI scores of  ≥ 16, suggesting a 100 % prevalence of dyspepsia.
In the curcumin group, 27.6 % of subjects reached a score of  < 16
at the end of trial while in the control group only 6.7 % of sub-
jects were categorized as non-dyspeptic at the end of study. The
number of subjects whose dyspepsia was resolved during the
DrugRes/2016-05-1190/22.6.2016/MPS Original Article

Fig. 1  Flow chart of the trial.

Flow Diagram
Enrollment
Assessed for eligibility (n=100)

Excluded (n=32)
♦ Not meeting inclusion criteria (n=32)

Randomized (n=68)

Allocation
Allocated to standard therapy plus curcumin Allocated to standard therapy plus placebo
(n=33) (n=35)

♦ Received allocated intervention (n=33) ♦Received allocated intervention (n=35)

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Follow-Up
Lost to follow-up (give reasons) (n=3) Lost to follow-up (give reasons) (n=5)

Reason: Not referring for the final visit and Reason: Not referring for the final visit and
urea breath test urea breath test

Analysis
Analysed (n=30) Analysed (n=30)

Table 1  Baseline characteristics of the study groups.

The impact of curcumin on H. pylori has been the subject of sev-
eral previous in vitro studies. It has been reported that curcumin
Curcumin Placebo p-Value suppresses IL-8 induction in H. pylori through inactivation of
Age (y) 35.03 ± 9.29 35.10 ± 8.96 0.978 NF-kappaB. IL-8 has a key role in H. pylori pathogenesis [29].
Female ( %) 16 (53.3 %) 18 (60.0 %) 0.795 These findings were confirmed by Foryst-Ludwig et al. in H.
Weight (kg) 76.50 ± 10.53 74.60 ± 13.49 0.546 pylori-infected epitheial cells [31] and by Sintara et al. in rat
Height (cm) 168.50 ± 8.50 166.37 ± 7.14 0.297 model of H. pylori infection [36]. In an experimental study in
BMI (kg/m2) 26.87 ± 2.28 26.79 ± 3.44 0.914 mice, De et al. showed the efficacy of curcumin in eradicating H.
Smoking ( %) 2 (6.7 %) 3 (10.0 %) 1.00
pylori infection. In the same study, the beneficial effects of cur-
Values are expressed as mean ± SD or number ( %). BMI: body mass index
cumin on healing of PU were shown [33]. In another animal
study, Kundu et al. reported that curcumin supplementation can
course of treatment was significantly higher in the curcumin vs. inhibit matrix metalloproteinases 3 and 9; 2 enzymes that are
placebo group (p = 0.042) ( ●
▶  Table 3). implicated in the pathogenesis of H. pylori. Interestingly, this
Curcumin was found to be safe and there was no report of any effect of curcumin was stronger than that of the standard triple
serious adverse event during the course of trial. There were 6 therapy [35]. Finally, another recent study on mouse model
reports of adverse events including diarrhea (one subject in each revealed that curcumin can inhibit all 84 up-regulated inflam-
group), headache (2 subjects in the curcumin group and one matory cytokines and chemokines in H. pylori-infected mucosa
subject in the placebo group) and vertigo (one subject in the pla- [37].
cebo group). These adverse events were mild or moderate and With respect to clinical studies, only few human studies have
did not lead to premature study withdrawal. explored the effects of curcumin in PU, and no study has yet
assessed the impact of adding curcumin as adjunct to anti-heli-
cobacter regimen in the context of a randomized controlled trial.
Discussion Di Mario et al. treated 25H. pylori-positive patients with func-
▼ tional dyspepsia with the combination of pantoprazol, N-acetyl-
This study was designed with the aim of evaluating the efficacy cystein, lactoferrin and curcumin. All of the patients had
of curcumin on the severity of dyspepsia and eradication of H. functional dyspepsia. They found that after 7 days of treatment,
pylori in patients with PU. Our results revealed that adding cur- only 3 patients were free of H. pylori but the severity of symp-
cumin to standard treatment of H. pylori-positive PU amelio- toms was reduced significantly [38]. Likely, Prucksunand et al. in
rates dyspepsia symptoms significantly. However, such an a clinical phase II study found that treatment with turmeric
adjunctive therapy does not have any enhancing effect on the H. (600 mg/day) for 4 weeks decreases PU symptoms. They showed
pylori eradication rate. As expected, curcumin was safe and well that 76 % of patients diagnosed with PU were free of ulcer 12
tolerated in this study. This finding is consistent with numerous weeks after the treatment [43]. In spite of the promising find-
previous clinical studies and further supports consideration of ings, both of the aforementioned studies was limited in its sin-
curcumin as “generally recognized as safe” for human use. gle-arm design which makes it difficult to attribute the observed

Khonche A et al. Curcumin for Peptic Ulcer …  Drug Res

 Original Article DrugRes/2016-05-1190/22.6.2016/MPS

Table 2  Within-group comparison of dyspepsia symptoms in the study groups.

Curcumin Placebo
Pre-treatment Post-treatment p-Value Pre-treatment Post-treatment p-Value
Stomach pain 3.67 ± 0.88 1.83 ± 0.38  < 0.001 3.57 ± 0.97 2.07 ± 045  < 0.001
Upper abdominal bloating 2.63 ± 1.10 1.40 ± 0.62  < 0.001 3.27 ± 1.05 2.20 ± 0.66  < 0.001
Upper abdominal dull ache 3.38 ± 0.62 1.57 ± 0.63  < 0.001 3.40 ± 0.67 2.10 ± 0.61  < 0.001
Stomach pain before meals 2.83 ± 0.79 1.40 ± 0.62  < 0.001 2.70 ± 0.79 1.80 ± 0.61  < 0.001
Stomach pain when anxious 2.33 ± 1.06 1.43 ± 0.57  < 0.001 2.77 ± 0.82 2.10 ± 0.71  < 0.001
Vomiting 1.13 ± 0.43 1.03 ± 0.18 0.083 1.07 ± 0.25 1.00 ± 0.00 0.157
Nausea 2.00 ± 0.74 1.13 ± 0.35  < 0.001 2.07 ± 0.87 1.30 ± 0.47  < 0.001
Belching 1.67 ± 0.80 1.10 ± 0.31 0.002 1.47 ± 0.57 1.30 ± 0.53 0.025
Acid regurgitation 1.73 ± 0.74 1.33 ± 0.48 0.003 1.50 ± 0.68 1.23 ± 0.43 0.011
Heartburn 4.17 ± 0.79 1.97 ± 0.18  < 0.001 4.47 ± 0.51 2.40 ± 0.50  < 0.001
Feeling of acidity in stomach 1.87 ± 0.86 1.20 ± 0.41  < 0.001 1.63 ± 0.67 1.27 ± 0.45 0.002
Loss of appetite 1.83 ± 1.12 1.17 ± 0.38 0.001 2.00 ± 0.87 1.53 ± 0.57 0.002

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Total score 29.41 ± 3.78 16.57 ± 1.59  < 0.001 29.90 ± 5.19 20.30 ± 3.14  < 0.001
Values are expressed as mean ± SD

Table 3  Comparison of dyspepsia symptoms between the study groups.

apparently no effect on the eradication rate of H. pylori. Owing
to the strong evidence on the safety and pleiotropic actions of
Curcumin Placebo p-Value curcumin in human use, this phytochemical could be considered
Stomach pain  − 1.83 ± 0.75  − 1.50 ± 0.94 0.151 as an efficacious adjunct in patients suffering from PU. However,
Upper abdominal bloating  − 1.23 ± 0.90  − 1.07 ± 0.74 0.366 future investigations are required to test the long-term efficacy
Upper abdominal dull ache  − 1.86 ± 0.69  − 1.30 ± 0.65 0.002 of curcumin in patients with dyspepsia, especially with respect
Stomach pain before meals  − 1.43 ± 0.82  − 0.90 ± 0.66 0.004 to the prevention of new H. pylori infections.
Stomach pain when anxious  − 0.90 ± 0.92  − 0.67 ± 0.66 0.404
Vomiting  − 1.00 ± 0.31  − 0.07 ± 0.25 0.643
Nausea  − 0.87 ± 0.73  − 0.77 ± 0.63 0.625
Acknowledgments
Belching  − 0.57 ± 0.77  − 0.17 ± 0.38 0.028
Acid regurgitation  − 0.40 ± 0.62  − 0.27 ± 0.52 0.377 ▼
Heartburn  − 2.20 ± 0.81  − 2.07 ± 0.52 0.254
This study was financially supported by Clinical Trial Research
Feeling of acidity in stomach  − 0.67 ± 0.71  − 0.37 ± 0.56 0.087 Center (Tehran, Iran). The authors gratefully acknowledge Sami
Loss of appetite  − 0.67 ± 0.84  − 0.47 ± 0.73 0.380 Labs LTD (Bangalore, India) for providing the drug material used
Total score  − 12.90 ± 2.81  − 9.60 ± 3.39  < 0.001 in this trial.
Values are expressed as mean ± SD

clinical benefit to curcumin or turmeric. The third trial was a
randomized one comparing the effects of standard triple therpy
(omeparazol, amoxicillin and metronidazole) vs. tumeric tablet
(containing an average of 40 mg curcumin) in H. pylori-positive
patients with chronic gastritis. Following a 4-week treatment
period, Koosirirat et al. found that H. pylori eradication and
reduction of IL-8 mRNA expression were significantly higher in
patients treated with standard medication compared with the
turmeric group. [39]. However, this latter study was limited in
not assessing clinical symptoms, and administration of a rela-
tively small dose of curcumin. Besides, intestinal and hepatic
glucuronidation has been suggested as a major reason for the
low oral bioavailability of curcumin in the crude and unfor-
mualted forms. Therefore, in the present study we co-adminis-
tered curcumin with piperine – the alkaloid extracted from
balck pepper or long pepper – which is a strong glucuronidase
inhibitor with known bioavailability-enhancing effects on cur-
cumin [40, 41]. Finally, Kim et al. showed that turmeric extract
reduces gastric acid via blocking H2 histamine receptors in an
experimental rats model [44]. This finding is in line with the
present results, and suggests that although curcumin could not
eradicate H. pylori, it could ameliorate PU symptoms possibly
through reduction of gastric acid secretion.
In summary, findings of the randomized controlled trial sug-
gested that adding curcumin on top of standard H. pylori treat-
ment regimen improves clinical symptoms of dyspepsia with
Conflict of Interest
▼
Muhammed Majeed is the CEO of Sabinsa Corporation and Sami
Labs Ltd.
Affiliations
1
 Baqiyatallah Research Center for Gastroenterology and Liver Disease,
Baqiyatallah University of Medical Sciences, Tehran, Iran
2
 Chemical Injuries Research Center, Baqiyatallah University of Medical
Sciences, Tehran, Iran
3
 Neurogenic Inflammation Research Center, Department of Modern Sciences
and Technologies, Mashhad University of Medical Sciences, Mashhad, Iran
4
 Sabinsa Inc, Princeton, NJ, United States
5
 Biotechnology Research Center, Mashhad University of Medical Sciences,
Mashhad, Iran
6
 Metabolic Research Centre, Royal Perth Hospital, School of Medicine and
Pharmacology, University of Western Australia, Perth, Australia.
References
1 Najm WI. Peptic ulcer disease. Primary Care: Clinics in Office Practice
2011; 38: 383–394
2 Ford A, Delaney B, Forman D et al. Eradication therapy for peptic ulcer
disease in Helicobacter pylori positive patients. The Cochrane Library
2007
3 Kuipers E. Helicobacter pylori and the risk and management of asso-
ciated diseases: gastritis, ulcer disease, atrophic gastritis and gastric
cancer. Alimentary pharmacology & therapeutics 1997; 11: 71–88
4 Vanni E, Bugianesi E, Kotronen A et al. From the metabolic syndrome to
NAFLD or vice versa? Digestive and Liver Disease 2010; 42: 320–330

Khonche A et al. Curcumin for Peptic Ulcer…  Drug Res

DrugRes/2016-05-1190/22.6.2016/MPS
5 Rinella M, Charlton M. The globalization of non-alcoholic fatty liver
disease – prevalence and impact on world health. Hepatology 2016
6 Chey WD, Wong BC. American College of Gastroenterology guideline
on the management of Helicobacter pylori infection. The American
journal of gastroenterology 2007; 102: 1808–1825
7 Sarkar A, De R, Mukhopadhyay AK. Curcumin as a potential therapeutic
candidate for Helicobacter pylori associated diseases. World journal
of gastroenterology 2016; 22: 2736
8 Momtazi AA, Derosa G, Maffioli P et al. Role of microRNAs in the Thera-
peutic Effects of Curcumin in Non-Cancer Diseases. Mol Diagn The
2016; May 30. [Epub ahead of print] Review. doi: 10.1007/s40291-
016-0202-7
9 Panahi Y, Badeli R, Karami GR et al. Investigation of the efficacy of
adjunctive therapy with bioavailability-boosted curcuminoids in
major depressive disorder. Phytotherapy Research 2015; 29: 17–21
10 Esmaily H, Sahebkar A, Iranshahi M et al. An investigation of the effects
of curcumin on anxiety and depression in obese individuals: A rand-
omized controlled trial. Chinese journal of integrative medicine 2015;
21: 332–338
11 Panahi Y, Alishiri GH, Parvin S et al. Mitigation of systemic oxidative
stress by curcuminoids in osteoarthritis: results of a randomized con-
trolled trial. Journal of dietary supplements 2015
12 Panahi Y, Rahimnia AR, Sharafi M et al. Curcuminoid treatment for
knee osteoarthritis: a randomized double-blind placebo-controlled
trial. Phytotherapy Research 2014; 28: 1625–1631
13 Panahi Y, Hosseini MS, Khalili N et al. Antioxidant and anti-inflamma-
tory effects of curcuminoid-piperine combination in subjects with
metabolic syndrome: A randomized controlled trial and an updated
meta-analysis. Clinical Nutrition 2015
14 Panahi Y, Khalili N, Hosseini MS et al. Lipid-modifying effects of adjunc-
tive therapy with curcuminoids-piperine combination in patients
with metabolic syndrome: Results of a randomized controlled trial.
Complementary therapies in medicine 2014; 22: 851–857
15 Sahebkar A. Curcuminoids for the management of hypertriglyceridae-
mia. Nature Reviews Cardiology 2014; 11: 123–123
16 Mohammadi A, Sahebkar A, Iranshahi M et al. Effects of supplemen-
tation with curcuminoids on dyslipidemia in obese patients: a ran-
domized crossover trial. Phytotherapy Research 2013; 27: 374–379
17 Panahi Y, Kianpour P, Mohtashami R et al. Curcumin lowers serum
lipids and uric acid in subjects with non-alcoholic fatty liver disease:
A randomized controlled trial. Journal of cardiovascular pharmacol-
ogy 2016
18 Rahmani S, Asgary S, Askari G et al. Treatment of Non-alcoholic Fatty
Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.
Phytother Res 2016; June 8. doi:10.1002/ptr.5659.
19 Sahebkar A. Dual effect of curcumin in preventing atherosclerosis:
the potential role of pro-oxidant-antioxidant mechanisms. Natural
product research 2014; 1–2
20 Sahebkar A. Molecular mechanisms for curcumin benefits against
ischemic injury. Fertility and sterility 2010; 94: e75–e76
21 Panahi Y, Ghanei M, Bashiri S et al. Short-term curcuminoid supple-
mentation for chronic pulmonary complications due to sulfur mustard
intoxication: positive results of a randomized double-blind placebo-
controlled trial. Drug research 2014
22 Panahi Y, Sahebkar A, Parvin S et al. A randomized controlled trial on
the anti-inflammatory effects of curcumin in patients with chronic
sulphur mustard-induced cutaneous complications. Annals of clinical
biochemistry 2012; 49: 580–588
23 Panahi Y, Ghanei M, Hajhashemi A et al. Effects of curcuminoids-pip-
erine combination on systemic oxidative stress, clinical symptoms and
quality of life in subjects with chronic pulmonary complications due
to sulfur mustard: a randomized controlled trial. Journal of dietary
supplements 2014
24 Panahi Y, Sahebkar A, Amiri M et al. Improvement of sulphur mustard-
induced chronic pruritus, quality of life and antioxidant status by
curcumin: results of a randomised, double-blind, placebo-controlled
trial. British Journal of Nutrition 2012; 108: 1272–1279
Original Article
25 Panahi Y, Saadat A, Beiraghdar F et al. Adjuvant therapy with bioavail-
ability-boosted curcuminoids suppresses systemic inflammation and
improves quality of life in patients with solid tumors: a randomized
double-blind placebo-controlled trial. Phytotherapy Research 2014;
28: 1461–1467
26 Sharma R, Gescher A, Steward W. Curcumin: the story so far. Euro-
pean journal of cancer 2005; 41: 1955–1968 doi: 10.1007/s40291-
016-0202-7
27 Sahebkar A. Are curcuminoids effective c-reactive protein-lowering
agents in clinical practice? evidence from a meta-analysis. Phyto-
therapy Research 2014; 28: 633–642
28 Panahi Y, Hosseini MS, Khalili N et al. Effects of supplementation
with curcumin on serum adipokine concentrations: a randomized
controlled trial. Nutrition 2016
29 Münzenmaier A, Lange C, Glocker E et al. A secreted/shed product of
Helicobacter pylori activates transcription factor nuclear factor-kappa
B. The Journal of Immunology 1997; 159: 6140–6147
30 Mahady G, Pendland S, Yun G et al. Turmeric (Curcuma longa) and cur-
cumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen.
Anticancer research 2001; 22: 4179–4181
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
31 Foryst-Ludwig A, Neumann M, Schneider-Brachert W et al. Curcumin
blocks NF-κB and the motogenic response in Helicobacter pylori-
infected epithelial cells. Biochemical and biophysical research com-
munications 2004; 316: 1065–1072
32 Han C, Wang L, Yu K et al. Biochemical characterization and inhibitor
discovery of shikimate dehydrogenase from Helicobacter pylori. Febs
Journal 2006; 273: 4682–4692
33 De R, Kundu P, Swarnakar S et al. Antimicrobial activity of curcumin
against Helicobacter pylori isolates from India and during infections in
mice. Antimicrobial agents and chemotherapy 2009; 53: 1592–1597
34 Zaidi SFH, Yamamoto T, Refaat A et al. Modulation of activation-induced
cytidine deaminase by curcumin in helicobacter pylori-infected gas-
tric epithelial cells. Helicobacter 2009; 14: 588–595
35 Kundu P, De R, Pal I et al. Curcumin alleviates matrix metalloprotein-
ase-3 and-9 activities during eradication of Helicobacter pylori infec-
tion in cultured cells and mice. PloS one 2011; 6: e16306
36 Sintara K, Thong-Ngam D, Patumraj S et al. Curcumin suppresses gas-
tric NF-kappaB activation and macromolecular leakage in Helicobac-
ter pylori-infected rats. World J Gastroenterol 2010; 16: 4039–4046
37 Santos AM, Lopes T, Oleastro M et al. Curcumin inhibits gastric inflam-
mation induced by Helicobacter pylori infection in a mouse model.
Nutrients 2015; 7: 306–320
38 Di Mario F, Cavallaro LG, Nouvenne A et al. A curcumin-based 1-week
triple therapy for eradication of helicobacter pylori infection: some-
thing to learn from failure? Helicobacter 2007; 12: 238–243
39 Koosirirat C, Linpisarn S, Changsom D et al. Investigation of the anti-
inflammatory effect of Curcuma longa in Helicobacter pylori-infected
patients. International immunopharmacology 2010; 10: 815–818
40 Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bio-
availability by piperine: evidence that piperine is a potent inhibitor
of drug metabolism. The Journal of pharmacology and experimental
therapeutics 1985; 232: 258–262
41 Shoba G, Joy D, Joseph T et al. Influence of piperine on the pharmacoki-
netics of curcumin in animals and human volunteers. Planta medica
1998; 64: 353–356
42 Hu WH, Lam KF, Wong YH et al. The Hong Kong index of dyspepsia: a
validated symptom severity questionnaire for patients with dyspep-
sia. J Gastroenterol Hepatol 2002; 17: 545–551
43 Prucksunand C, Indrasukhsri B, Leethochawalit M et al. Phase II clinical
trial on effect of the long turmeric (Curcuma longa Linn.) on healing of
peptic ulcer. Southeast Asian journal of tropical medicine and public
health 2001; 32: 208–215
44 Kim D-C, Kim S-H, Choi B-H et al. Curcuma longa extract protects
against gastric ulcers by blocking H2 histamine receptors. Biological
and Pharmaceutical Bulletin 2005; 28: 2220–2224
Khonche A et al. Curcumin for Peptic Ulcer …  Drug Res