Antidiabetic and antioxidant activities of Toddalia asiatica (L.) Lam. Leaves in Streptozotocin induced diabetic rats

Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
Journal of ethnopharmacology (Impact Factor: 2.94). 07/2012; 143(2):515-23. DOI: 10.1016/j.jep.2012.07.006
Source: PubMed

ABSTRACT The leaves of Toddalia asiatica (L.) Lam. have been utilized traditionally for the cure of diabetes.
The present study was aimed to assess the antidiabetic and antioxidant effects of T. asiatica leaves in Streptozotocin (STZ) induced diabetic rats.
The phytochemical screening, total phenolic content, HPLC analysis, acute toxicity study and oral glucose tolerance test were carried out. Glucose lowering effect of the hexane, ethyl acetate and methanol extracts of T. asiatica leaves was studied in STZ-induced diabetic rats. The antidiabetic and antioxidant activities were studied for the ethyl acetate extract. The effects of extracts on blood glucose, body weight, plasma insulin, total protein, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and activities of SOD, CAT and GPx were analyzed.
T. asiatica leaves ethyl acetate extract (TALEe) showed highly significant blood glucose lowering effect. Phytochemical evaluation of TALEe showed the presence of alkaloids, terpenoids, cumarins, flavonoids and phenolic compounds. The total phenolic content of TALEe was 126mg of gallic acid equivalents/g extract. HPLC analysis revealed the presence of flindersine and ulopterol. Acute toxicity study of TALEe revealed no death or toxicity. The oral glucose tolerance test showed lowered area under curve (AUC(glucose)) values in TALEe treated rats. After treatment with TALEe (250 and 500mg/kg) for 28 days there was a significant decrease in blood glucose, plasma enzymes (SGOT, SGPT and ALP) and significant increase in body weight, total protein, serum insulin and liver glycogen levels in treated diabetic rats. The activities of antioxidant enzymes SOD, CAT and GPx were reversed to near normal in treated diabetic rats. Histopathology of pancreas in TALEe treated groups showed regeneration of β-cells.
The results of the experiments showed that TALEe exerted significant antidiabetic and antioxidant effects in STZ-induced diabetic rats justifying its traditional use.

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    • "This could be due to the result of improved glycemic control exerted by 1 and 2. Reduction in total protein content was observed in diabetic rats which might be due to progressive proteinuria (Latha and Daisy 2011). In experimental diabetes, distinct metabolic renal alterations are demonstrable, leading to a negative nitrogen balance, enhanced proteolysis and lowered protein synthesis (Irudayaraj et al. 2012). The plasma protein level was improved in diabetic rats after treatment with test compounds 1 and 2. Liver is the vital organ of metabolism, detoxification, storage and excretion of xenobiotics and their metabolites. "
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    ABSTRACT: 1, 2, 8-trihydroxy-6-methoxy xanthone (1) and 1, 2- dihydroxy-6-methoxyxanthone-8-O-β-d-xylopyranosyl (2) are the main constituents of petroleum ether and ethyl acetate extracts from Swertia corymbosa (Gentinaceae), a medicinal plant used in Indian traditional system for the treatment of diabetes. The present study was designed to examine the antihypoglycemic, antihyperlipidemic and antioxidant effect of compounds 1 and 2 in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (60mg/kgb.w.). The isolated compounds 1 and 2 at a dose of 50mg/kgb.w., produced the maximum fall of 83% in the blood glucose level in the diabetic rats after 3h of the treatment. The administration of 1 and 2 (50mg/kgb.w.) daily for 28 days in STZ induced diabetic rats, resulted in a significant decrease in blood glucose, glycosylated hemoglobin, SGOT, SGPT, ALP serum urea and creatinine with significant rise in plasma insulin level. Test compounds 1 and 2 showed antihyperlipidemic activities as evidenced by significant decrease in serum TC, TG, LDL-C, VLDL-C levels coupled together with elevation of HDL-C level in diabetic treated rats when compared to diabetic untreated rats, indicate the protective role against liver and kidney damage. The results of histopathology also showed 1 and 2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like glucokinase (PDB ID: 1V4S), fructose-1, 6-bisphosphatase 1 (PDB ID: 2JJK) 11-β-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction. The ligand pose with 2BEL and SUR1 protein target of ligand 2 gave the best binding conformation. Hence 1 and 2 can be considered for developing into a potent antidiabetic drug.
    Phytomedicine 09/2014; 21(11):1237–1248. DOI:10.1016/j.phymed.2014.06.011 · 2.88 Impact Factor
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    • "The activities of antioxidant enzymes SOD, CAT and GPx were reversed to near normal in the treated diabetic rats. Histopathology of pancreas in the extract treated groups`-showed regeneration of β-cells of Langerhans (Irudayaraj, et al., 2012). "
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    ABSTRACT: Plants have been used by mankind to alleviate various ailments for several millennia. The World Health Organization (WHO) estimates that approximately 80 percent of the people especially in the developing countries use herbal medicine for their primary health care (WHO, 2002). Interest and research into the pharmacological effects of the various plant extracts has risen after the realization of their therapeutic potential. Toddalia asiatica is a monotypic genus which has been used as folklore remedy for malaria, pain, fever and respiratory problems especially in Africa. Several phytochemicals isolated from this species includes coumarins, quinolines, triterpenoids, phenanthridine and alkaloids. Extract from T. asiatica were shown to possess anti-inflammatory, analgesic, antipyretic, antimicrobial, antifungal, antimalarial, larvicidal, spasmolytic, cardiovascular and antitumor activity. Traditional herbs and knowledge when tested scientifically can provide new and effective pharmacological agents. Keywords: Toddalia; phytochemical; pharmacological
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