Rajesh Mandade et al.

, IJSID, 2012, 2 (5), 502-510

ISSN:2249-5347

IJSID

International Journal of Science Innovations and Discoveries

Research Article

An International peer Review Journal for Science

Available online through www.ijsidonline.info

RATS AND THE POSSIBLE MORPHOLOGICAL CHANGES IN THE LIVER AND KIDNEY

PROTECTIVE EFFECTS OF CARTHAMUS TINCTORIUS ON STREPTOZOTOCIN-INDUCED DIABETIC COMPLICATIONS IN Research Student, Pharmacology Department, J.J.T. University, Jhunjhunu Rajasthan, India Rajesh Mandade

Received: 26.10.2012 Accepted: 14.11.2012

*Corresponding Author

Objectives: Medicinal plants play a major role in the management of Diabetes mellitus ABSTRACT especially in developing countries. The present study investigated the possible therapeutic in streptozotocin (STZ) induced diabetes mellitus in rats. intraperitoneal (i.p.) injection of streptozotocin (STZ) (65 mg/kg). The rats were divided

effects of Carthamus tinctorius (C. tinctorius) crude extract on certain biochemical markers Materials and Methods: Diabetes was induced in Wistar albino rats of either sex by four groups as follows: I control, II diabetic control and III diabetic group treated with 400

mg/kg body weight crude extract of C. tinctorius IV diabetic group treated with Insulin 6 Address: Name: Rajesh mandade Place: Rajastan, India E-mail: raj_mandade@rediffmail.com units/kg body weight of rats /day. The effects of an crude extract of C. tinctorius aerial part on blood glucose, albumin, albumin/globulin ratio, urea, insulin, C-peptide, uric acid and creatinine and the activities of diagnostic marker enzymes aspartate aminotransferase, examined in the plasma, liver and kidney tissues of control and experimental groups. INTRODUCTION enzymes to near control levels. significantly reduced blood glucose, urea, uric acid and creatinine, but increased the alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase were activities of insulin, C-peptide, albumin, albumin/globulin ratio and restored all marker antihyperglycaemic effect and consequently may alleviate liver and renal damage associated with STZ-induced diabetes mellitus in rats. Rats.

Results: Oral administration of C. tinctorius crude extract to diabetic rats for 6 weeks

INTRODUCTION Conclusion: The present results shown that C. tinctorius crude extract has an
Key Words: C. tinctorius, Diabetes complications, Insulin, Blood Glucose, Streptozotocin,

International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

502

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510 Organization predicts that 300 millions of people will have diabetes mellitus by the year 2025 hyperglycemia, glycosuria and several microvascular and macro vascular complications
[2, 3].

associated with glucose metabolism resulting from defects in insulin secretion and action. It is characterized by atherosclerosis [6]. There is also possibility of liver damage in diabetes due to increased gluconeogenesis and ketogenesis.

Diabetes mellitus (DM) is a health problem affecting millions of individuals worldwide. The World Health INTRODUCTION
[1].

linked to oxidative stress induced by hyperglycemia which overcomes the bodys natural anti-oxidant system [4, 5]. In the later nitrogen from most organs. Increased urea nitrogen production in DM may be accounted for by enhanced catabolism of both drugs have undesirable side effects
[7].

stages of diabetes, lipid metabolism is affected and seen as hyperlipidemia and hypercholesterolemia which are risk factors in liver and plasma proteins. Management of DM without any side effects is still a challenge to the medical system. There is an glucosidase inhibitors in addition to insulin. However, due to unwanted side effects the efficacies of these compounds are scientific investigation due to a lack of mechanism-based available in vitro assays management of diseases all over the world coagulant flavonoids
[12], [16], [10], [9].

The complications of diabetes are

Diabetes is a disease

increasing demand by patients to use natural products with antidiabetic activity, because insulin and oral hypoglycaemic

DM is grossly reflected by profound changes in protein metabolism and by a negative nitrogen balance and loss of

hyperglycemia by the use of biguanides, thiazolidinediones, sulphonylureas, Diphenylalanine derivatives, meglitinides and debatable and there is a demand for new compounds for the treatment of diabetes [8]. Hence, plants have been suggested as a rich, as yet unexplored source of potentially useful anti diabetic drugs. However, only a few have been subjected to detailed demonstrated anti-myocardial ischemia effects improve neuropsychological disorders antioxidant and neuroprotective
[18]. [11].

Currently, the treatment of diabetes mainly involves a sustained reduction in

Carthamus tinctorius L. (Safflower) has long been used as Chinese medicine in clinics to treat cardiovascular disease, and has electro-physiological abnormalities induced by hydrogen peroxide in guinea pig ventricular myocytes diabetic rats, and the possible changes in the liver and kidney. Collection and authentication of plant material lignans, triterpene alcohols, and polysaccharides among others. Safflower has also been reported to prevent
[17]. [13, 14],

historically; the use of medicinal plants is as old as mankind and medicine. antiulcer
[15].

Safflower also possesses other pharmacological effects, including antiThe chemical constituents in safflower are reported to be It can be used to

Medicinal plants are widely used in

The present study was performed to assess the antidiabetic effects of extract of C. tinctorius on streptozotocin-induced MATERIALS AND METHODS Aerial part of Carthamus tinctorius L. were collected in the month of April from the Hingoli district of Maharashtra

India. The plant was identified and authenticated by Dr. Miss. A. Chaturvedi, Post Graduate Teaching Department of Botany, Rashtra Santa Tukadoji Maharaj Nagpur University Nagpur, India, where a voucher specimen (No. 9715) of the plant has been kept in the herbarium. Preparation of crude extract The plant materials were cleaned, shade dried and coarsely powdered mechanically. The powdered material was

soaked in 70% aqueous-methanol for 3 days with occasional shaking. It was filtered through a muslin cloth and then through a International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

filter paper. This procedure was repeated thrice and the combined filtrate was evaporated on a rotary evaporator under

503

reduced pressure to a thick, semi-solid mass of dark brown color, i.e. the crude extract (Co. Cr), yielding approximately 6.1%
[19].

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510

Selection of animals:

approved the experimental protocol; animals were maintained under standard conditions in an animal house approved by access to water.

Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA). Albino rats were used in this project was obtained from the Animal House of S.N.Institute of Pharmacy, Pusad. The animals were housed in Poly propylene Acute toxicity studies Rats were kept overnight fasting prior to drug administration. A total of five animals were used which received a

Wistar albino rats of either sex weighing between 160-180 gm were used. Institutional Animal Ethics Committee

cages and maintained at 24C 2C under 12h light/ dark cycle and were feed ad libitum with standard pellet diet and had free single oral dose (2,000 mg/kg body weight) of Carthamus tinctorius L. extract. After the administration of extract, food was side observations included changes in skin and fur, eyes and mucous membrane (nasal) and also respiratory rate, circulatory determined over a period of 2 weeks (OECD 2001c). Selection of dose of the extract carried out at dose 400 mg/kg body weight. Experimental Procedure:

withheld for further 34 h. Animals were observed individually at least once during the first 30 min after dosing, periodically

during the first 24 h (with special attention during the first 4 h) and daily thereafter for a period of 14 days. Once daily cage

(heart rate and blood pressure), autonomic (salivation, lacrimation, perspiration, piloerection, urinary incontinence, and defecation) and central nervous system (ptosis, drowsiness, gait, tremors and convulsion) changes. Mortality, if any, was LD50 was done as per OECD guidelines for fixing the dose for biological evaluation. The LD50 of the extract as per

OECD guidelines falls under class four values with no signs of acute toxicity at 2,000 mg/kg. The biological evaluation was distributed into four groups as follows: group I control, group II diabetic control and group III diabetic treated with 400 mg/kg group II, III and IV were rendered diabetic by a single intraperitoneal (i.p.) injection of 65 mg/kg of streptozotocin (STZ) was drawn from the tail of conscious rats and the glucose content was estimated with glucometer. Only those rats with blood glucose above 250 mg/dl were selected for the study. 15 days after the STZ injection, animals of group III and IV received extract of C. tinctorius (400 mg/kg) and insulin (6unit/kg) for 6 weeks. free filter paper, and the organ weights were measured
[21].

body weight extract of C. tinctorius IV diabetic group treated with Insulin 6 units/kg body weight of rats /day. Animals of freshly prepared in 0.1M of citrate buffer (pH 4.5). Group I was injected with buffer alone [20]. After 72 h, of STZ injection blood At the end of the experiment, blood was collected into heparinised tubes, and the plasma and serum were separated by and Creatinine were estimated using a commercial diagnostic kit (Ranbaxy Laboratories, New Delhi, India). The albumin and globulin contents were estimated by the method described by Reinhold. International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

The animals, irrespective of sex, between 2-3 months of age with body weight ranging between 160 to 180 g were

centrifugation. The liver and kidney were quickly removed, washed in ice-cold, isotonic saline and blotted individually on ash7.4. The homogenate was used for the estimations of proteins, enzymes, and other parameters. Blood glucose, urea, uric acid The tissues were then homogenized in 0.1 M TrisHCl buffer, pH

504

(-GT) was assayed by the method of Rosalki and Rau. The protein content in the plasma, liver and kidney were estimated by the method of Lowry. All spectrophotometric measurements were carried out in a UV-visible spectrophotometer. for eight animals in each group.

The enzymes, AST, ALT and ALP, were assayed by the method of King and Armstrong and -glutamyl transpeptidase Hypothesis testing methods included one way analysis of variance (ANOVA) followed by least significant differences RESULTS

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510

test. P-values of less than 0.05 were considered to indicate statistical significance. All the results were expressed as mean SD diabetic rats when compared to control rats. Administration of C. tinctorius (400 mg/kg) and insulin to diabetic rats significantly decreased the level of blood glucose to near control level. Table 1 demonstrates the levels of protein, plasma

albumin and albumin/globulin ratio in control and STZ-diabetic rats. The level of protein in plasma was found to be reduced in diabetic animals (p < 0.05) when compared to control animals. The lowered level of protein, after C. tinctorius treatment, diabetic rats.

A significant increase in the level of blood glucose, a decrease in plasma insulin and C-peptide were observed in

increased to near control. The levels of albumin and albumin/globulin ratio in plasma were decreased in diabetic animals. TABLE-1

These lowered levels of plasma albumin and albumin/globulin ratio level were restored significantly in C. tinctorius-treated Group parameter Control Diabetic control Diabetic + Insulin Diabetic + C. tinctorius Blood glucose (mg/dl) 96.0 6.6 292.74 5.3* 92.24.2* 105 6.3* Albumin (g/dl) 4.09 0.40 1.53 0.20* 3.480.14* 3.52 0.22* Albumin/globulin ratio 1.16 0.12 0.67 0.13* 1.0 0.1* 0.95 0.23* `Blood urea nitrogen (mg/dl) 28.6 2.0 45.0 4.1* 21.31.4* 31.4 2.0* Creatinine (mg/dl) 0.98 0.08 2.22 0.25* 1.100.04* 1.37 0.5* Plasma insulin (U/ml) 15.7 0.76 5.900.45* 11.90.65* 12.00.62* C-peptide (pmol/L) 257.411.9 153.39.85* 225.38.7* 234.39.75* Urinary albumin (mg/day) 0.14 0.02 1.6 0.4* 1.120.04* 0.72 0.2* Uric acid (mg/dl) 1.25 0.4 2.5 0.2* 1.100.06* 1.36 0.15* Protein (g/dl) 6.90 0.84 4.30 0.75* 6.900.64* 6.72 0.38* Values are given as mean SD for groups of eight animals each. Values are statistically significant at *p < 0.05. Diabetic rats rats were compared with diabetic rats. control animals. Oral administration of C. tinctorius extract for 6 weeks significantly lowered urea, uric acid and Creatinine STZ-diabetic rats. The activities of these enzymes were found to be significantly increased (p < 0.05) in the plasma and liver of AST, ALT, ALP and -GT in the plasma, liver and kidney of diabetic rats. treated diabetic rats were compared with diabetic rats. diabetic rats. In the kidney of diabetic animals, the activities of ALP and -GT were increased, while the activities of AST and Values are given as mean SD for groups of eight animals each. Values are statistically significant at *p < 0.05. ALT were not altered. Oral administration of C. tinctorius for six weeks resulted in the near normalization of the activities of

were compared with control rats; C. tinctorius -treated diabetic rats were compared with diabetic rats; insulin-treated diabetic levels in STZ-diabetic rats. Table 2 shows the activities of AST, ALT, ALP and -GT in plasma, liver and kidney of control and Urea, uric acid, and Creatinine levels were significantly elevated in STZ-diabetic rats (p < 0.05) when compared to

Diabetic rats were compared with control rats; C. tinctorius -treated diabetic rats were compared with diabetic rats; insulinInternational Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

505

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510 TABLE-2 Groups Control Diabetic Diabetic+ Insulin Diabetic + C. tinctorius Plasma AST 72.2 6.72 110.1 6.31* 81.2 1.90* 82.0 3.18* ALT 31.3 2.0 62.2 4.30* 35.5 2.75* 37.7 2.34* ALP 74.4 4.52 136.1 5.41* 83.9 4.42* 86.5 3.82* -GT 11.7 1.00 24.5 2.54* 16.7 1.52* 16.8 1.88* Kidney AST 783.0 11.4 743.4 13.3* 786.2 9.8* 780.5 8.80* ALT 831.4 16.4 806.4 19.9* 828.8 14.5* 822.4 15.22* ALP 0.21 0.02 0.43 0.06* 0.29 0.02* 0.32 0.04* -GT 2.65 0.20 5.56 0.26* 3.00 0.16* 3.21 0.17* Liver AST 752.0 15.9 958.4 22.4* 742.4 14.4* 755.2 12.7* ALT 905.4 15.5 1237.6 18.6* 932.3 12.9* 975.6 16.8* ALP 0.14 0.02 0.29 0.04* 0.20 0.02* 0.22 0.01* -GT 3.38 0.34 5.57 0.39* 3.40 0.35* 3.64 0.30* Units of measurement (per L) for AST and ALT: mol of pyruvate liberated/hr; ALP: mol of phenol liberated/min; -

GT: mol of pnitroaniline liberated/min. Histological results:

Liver: By light microscopy, liver of the STZ treated diabetic rats showed 2 - 3 foci of interlobular lymphocytes predominant inflammatory cells infiltration per 100 magnifications as compared by necrosis and apoptosis of few hepatocytes. Mild inflammation and lymphocytes were replaced by few eosinophils, the hepatic tissue appeared somewhat like the control and the Insulin treated groups (Figure 1). the diabetic rats treated by C. tinctorius crude extract, showed gradual significant reduction in parenchymal and portal

lymphocytic infiltration and congested vessel intlemajority of portal spaces were noted. Histological examination of livers of

Figure 1: Photomicrograph of liver section of rats, control (A) and STZ (B), C. tinctorius extract treated (C). The specimens International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012 were stained with Hematoxylin and Eosin.

506

Kidney: Histological examination of the STZ-induced diabetic rats renal tissue compared to the control groups revealed mild extract these pathologic changes improved toward to the Insulin treated groups (Figure 2).

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510

increase in mesangial cells and matrix of glumeroli. Hyaline thickening of some arteriole wall was noted. By C. tinctorius crude

Figure 2: Photomicrograph of Kidney section of rats, control (A) and STZ (B), C. tinctorius extract treated (C). The specimens were stained with Hematoxylin and Eosin. DISCUSSION

and kidney of STZ-diabetic rats. We have observed a significant decrease in blood glucose in C. tinctorius-treated diabetic rats, when compared with diabetic control rats. The optimum dosage (400 mg/kg) was standardized and confirmed by a previous study with significant hypoglycaemic activity peripheral tissue [23]. This was clearly evidenced by the increased level of insulin in diabetic rats treated with C. tinctorius.
[22].

The present investigation indicates the hypoglycaemic and protective effects of C. tinctorius crude extract in the liver The possible mechanism of C. tinctorius hypoglycaemic action may be

through potentiating of pancreatic secretion of insulin from -cell of islets or due to enhanced transport of blood glucose to the results obtained by other scientists [24].The decrease in protein and albumin may be due to microproteinuria and albuminuria, elevation in the plasma total protein and albumin levels as compared with their normal levels. Such improvement of serum C-peptide and insulin are the products of the enzymatic cleavage of proinsulin and secreted into the circulation in equimolar International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

which are important clinical markers of diabetic nephropathy and/or may be due to increased protein catabolism. The results of the present study demonstrated that the treatment of diabetic rats with the extract of C. tinctorius caused a noticeable experimentally diabetic rats [25]. It has been established that insulin stimulates the incorporation of amino acids into proteins. protein and albumin was previously observed after the oral administration of Balanites aegyptiaca (B. aegyptiaca) to concentrations. The measurement of both C-peptide and insulin levels have been reported to be a valuable index of insulin

Reduction in plasma total protein and albumin level was observed in diabetic rats and this is consistent with the

507

secretion rather than insulin alone. In this study, the plasma C-peptide and insulin levels were significantly higher in the C. tinctorius treated group than in the diabetic control group. glucose regulation, including elevated glucose and glycosylated protein tissue levels, haemodynamics changes within the kidney tissue, and increased oxidative stress. The STZ-induced diabetic rats exhibited significantly higher plasma urea, uric acid and creatinine levels compared to the diabetic control group. However, the C. tinctorius supplement lowered these plasma values to a control range. Significant elevations in serum creatinine and urea levels indicate an impaired renal function of diabetic animals [26]. Thus, it would appear that the C. tinctorius supplement lowered the plasma urea, uric acid and creatinine previous studies. The AST, ALT and ALP activities are known as cytosolic marker enzymes reflecting hepatocellular necrosis as they are
[29, 30].

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510

The plasma levels of urea, uric acid and creatinine were measured, as DM also causes renal damage due to abnormal

levels by enhancing the renal function that is generally impaired in diabetic rats. These results are in agreement with other released into the blood after cell membrane damage [27, 28]. The increase in the activities of plasma AST, ALT and ALP indicated that DM may induce hepatic dysfunction. The enzymes directly associated with the conversion of amino acids to keto acids are AST and ALT, and are increased in the diabetic conditions enzyme activities. The increased protein catabolism accompanying gluconeogenesis and urea formation that are seen in the

diabetic state might be responsible for the elevation of these tissue transaminases. The rise in the activity of ALT is due to enzymes, which were brought back to near normal value by C. tinctorius treatment. This result shows the normalizing effects diabetic rats. Plant antioxidants are able to restore and regenerate pancreatic B cells increased significantly
[32]. [31].

hepatocellular damage and is usually accompanied by a rise in AST. This might be the reason for the elevated activities of these fenugreek, garlic and onion show that in diabetic rats treated with anti-oxidants the number of Langerhans islets has potential, suggesting that it could be useful in prevention of diseases in which free radicals are implicated. Some studies have thus elevating the insulin level. shown that flavonoids are able to decrease plasma glucose levels. Taking into accounts these results, we conclude that one of the mechanisms involved in hypoglycemic effect of Carthamus tinctorius is regeneration and restoration of Langerhans islets, treatment restored the activity of this enzyme to near normal by reducing its induction in DM. -GT catalyses the transfer of The results from the studies on

Treatment with C. tinctorius or insulin normalized these

of C. tinctorius on hepatocellular damage and suppression of gluconeogenesis. Elevated activity of ALP was observed in STZC. tinctorius constitutes a good source of antioxidant compounds with free radical-scavenging

the -glutamyl group from -glutamyl peptides to another peptide or L-amino acids or to water. The assay of -GT is a helpful adjunct in detecting hepatic damage. A highly significant elevation in the activity of -GT was observed in plasma, liver and expression was found in the liver of diabetic rats. Elevated activity of -GT in plasma takes place as a result of hepatic possible prevention of necrosis by C. tinctorius. In conclusion, C. tinctorius aerial part crude extract lowered blood glucose with a simultaneous increase in the plasma

The increased activity of this enzyme in plasma may be a result of diabetes-induced damage to the tissues. C. tinctorius

kidney of STZ-induced diabetic rats. This is in accord with earlier investigations, wherein a dramatic increase in -GT induction of the enzyme. In addition, hepatocellular damage or cholestasis may also contribute to the elevation in the activity. Increased activity of -GT in STZ-induced diabetic rats was lowered to near normal by C. tinctorius treatment that indicates the insulin and C-peptide levels. In addition, C. tinctorius extract could influence protein metabolism and marker enzymes in STZinduced diabetic rats. Extract also protect liver and Kidney from damage due to diabetes. International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

508

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510 1. 2. 3. 4. 5. 6. 7. 8. 9. Pradeepa R, Mohan V. The changing of the diabetes epidemic implications for India. Indian Journal of Medical REFERENCES Research 2002; 116:12132. Brownlee M. Biochemistry and molecular cell biology of diabetic complication. Nature 2001; 414:813-20. diaease in diabetes. Fron. Biosci 2003; 8:750-68. Diabetic Wistar Rats. Journal of Pharmacology and Toxicology 2008; 3:311-17.

Virella-Lopes Mf, Virella G. The role of immune and inflammatory processes in the development of macrovascular Udoh EA, Iya N, Okon E, Mary N. Red cell catalase activity in diabetes. Pak. J. Nutr 2007; 6: 511-15. Schwartz SL. Diabetes and dyslipidemias. Diabetes obes. Metab 2006; 8:355-64. in experimental ethanol toxicity. Phytother. Res 2003; 17:737-43. 10:369-78 santalinus L. on blood glucose level in experimental animals. J Ethnopharmacol 2001; 74: 69-74.

Anilkumar MD, Naseeruddin MI. Protective Effects of Andrographis paniculata Against Endothelial Dysfunction in Kameswara RB, Guiri R, Kesavulu MM, Apparao CH. Effect of oral administration of bark extracts of Pterocarpus Thirunavukkarasu V, Anuradha CV, Viswanathan P. Protective effect of fenugreek (Trigonella foenum graecum) seeds Saxena A, Vikram NK. Role of selected Indian plants in management of type 2 diabetes. J. Altern. Comp. Med 2004; on rat liver and kidney functions. J. Pharmacol. Toxicol 2007; 2:373-79. Pharmacol. Bull 2006; 53337 silica gel adsorption. Chin Pharm J 2002; 37:10609 injury. Exp Brain Res 2007; 177:53339

10. Aliyu R, Adebayo AH, Gatsing D, Garba IH. The effects of ethanolic leaf extract of Commiphora Africana (Burseraceae)

11. Li XZ, Liu JX, Shang XH, Fu JH. Protective effects of hydroxysafflor yellow A on acute myocardial ischemia in dogs. Chin. 12. Zang BX, Wu W, Li WR, Li JR, Li JS, Wang YQ. Study on the anticoagulation effect of gross safflor yellow prepared by 13. Wang CY, Zhang DL, Li GS, Liu JT, Tian JW, Fu FH, et al., Neuroprotective effects of safflor yellow B on brain ischemic volume and acidity of stimulated gastric secretion. Orient Pharm Exp Med 2011; 11 (4):293-98 Free Radicals and Antioxidants 2011; 1(3):87-93. different cultivars of Carthamus tinctorius L. Biosci Biotechnol Biochem 2000; 64:158899 myocytes induced by oxygen-derived free radical. Chin J Clin Rehabil 2004; 8:681012 Ethnopharmacol 2009; 6:124(1):11624 Carthamus oxycantha. Phytother Res 2005; 19:67983

14. Mandade R, Sreenivas SA, Sakarkar DM, Wanare R. Pharmacological effects of extract of Carthamus tinctorius on 15. Mandade R, Sreenivas SA, Choudhury A. Radical Scavenging and Antioxidant Activity of Carthamus tinctorius Extracts. 16. Kazuma K, Takahashi T, Sato K, Takeuchi H, Matsu-moto TTO. Quinochalcones and flavonoids from fresh florets in

17. Shan HL, Yang BF, Li YH, Li YR, Xu CQ. Effect of safflower yellow pigment on abnormal electro-physiology of cardiac 19. Gilani AH, Bukhari IA, Khan RA, Khan A, Ullah F, Ahmad VU. Cholinomimetic and calcium channel blocking activities of nephropathy in rats. Pharmacology 2006; 76 (2):172-78.

18. Zhao G, Zheng XW, Gai Y, Chu WJ, Qin GW, Guo LH. Safflower extracts functionally regulate monoamine transporters. J. 20. Sharma S, Anjanevulu M, Kulkarni SK, Chopra K. Resveratrol a polyphenolic phytoalexin, attenuates diabetic International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

509

21. Atangwho IJ, Ebong PE, Egbung GE, Eteng MU, Eyong EU. Effect of Vernonia amygdalina Del. on liver funtion in alloxan22. Paramesha M, Ramesh CK, Krishna V, Parvathi KMM, Kuppast IJ. Antihyperglycemic activity of methanolic extract of carthamus tinctorius L. annigere-2. Asian journal of experimental science 2009; 23(3):497-02. Diabetic Rats. Journal of Pharmacology and Toxicology 2008; 3: 1-10. insulindependent diabetes in children. Acta Paediatr Suppl 1997; 418:7-10. rats. J Cell Mol Med 2003; 7:322-29. 23. Saravanan G, Pari L. Hypoglycaemic and Antihyperglycaemic Effect of Syzygium cumini Bark in Streptozotocin-Induced 24. Tuvemo T, Ewald U, Kobboh M, Proos LA. Serum magnesium and protein concentrations during the first five years of 25. Mansour HA, Newairy AA. Amelioration of impaired renal function associated with diabetes by Balanites aegyptiaca 26. Shinde UA, Goyal RK. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic induced diabetic rats. Indian J Exp Biol 2010; 48:165-73. fruits in streptozotocin-induced diabetic rats. J Med Res Inst 2000; 21:115-25. induced hyper glycemic rats. J. Pharm. Bioresour 2007; 4(1):1-7.

Rajesh Mandade et al., IJSID, 2012, 2 (5), 502-510

27. Kaimal S, Sujatha KS, George S. Hypolipidaemic and antioxidant effects of fruits of Musa AAA (Chenkadali) in alloxan hydroxytyrosol from olive mill waste in vitro and in rats. Chem Biol Interact 2009; 180:421-32. alloxaninduced diabetic mice. Indian J Biochem Biophys 2009; 46:99-05. and Carthamus tinctorius extracts. Chem Biodivers 2010; 7:383-91. alloxan induced diabetic rats. Food Chem Toxicol 2005; 43:57-63.

28. Hamden K, Allouche N, Damak M, Elfeki A. Hypoglycemic and antioxidant effects of phenolic extracts and purified 30. Han SY, Li HX, Bai CC, Wang L, Tu PF. Component analysis and free radical-scavenging potential of Panax notoginseng 31. Venkatesh S, Reddy MB, Reddy DG, Mullangi R, Lakshman M. Antihyperglycemic and hypolipidemic effects of Helicteres isora roots in alloxan-induced diabetic rats: A possible mechanism of action. J Nat Med 2010; 64:295-04. 32. Eldemerdash FM, Yousef MI, Abou ElNaga NI. Biochemical study on the hypoglycemic effects of onion and garlic in

29. Sharma N, Garg V. Antidiabetic and antioxidant potential of ethanolic extract of Butea monosperma leaves in

International Journal of Science Innovations and Discoveries, Volume 2, Issue 5, September-October 2012

510