PROTECTIVE ROLE OF BERBERINE IN AMELIORATING DIABETIC COMPLICATIONS IN STREPTOZOTOCIN-HIGH FAT DIET MODEL IN EXPERIMENTAL ANIMALS

Objective: Diabetes mellitus is a serious, complex metabolic disorder and growing health threat disease in the world. Berberine, one of the main constituent in Rhizoma coptidis is widely used in the treatment of diabetes. Potential of berberine in the management of diabetic complications, namely diabetic nephropathy and cardiomyopathy, is however, not yet explored. The present study was, therefore, undertaken to explore the potential of berberine for the management of diabetic nephropathy and diabetic cardiomyopathy in high-fat diet (HFD) and low dose streptozotocin (STZ) induced diabetes in rats. Methods: Rats were fed a high-fat diet for 4 w followed by a single intraperitoneal dose of streptozotocin (35 mg/kg). Animals were divided in five groups. Berberine was given orally in two different dose levels (75 mg/kg and 150 mg/kg) for 28 d. Metformin (100 mg/kg) was used as a standard antidiabetic drug. At the end of the study, parameters evaluated includes glycemic profile, lipid profile, left ventricular indices, urinary protein, serum creatinine, blood urea nitrogen and cardiac antioxidants. Histopathology of kidney and pancreas was carried out. Results: Berberine treated groups showed a significant decrease in fasting blood glucose, glycosylated Hb, creatinine, blood urea nitrogen and urinary total proteins, whereas there was a significant improvement in serum insulin, liver glycogen, skeletal muscle glycogen and cardiac antioxidant enzymes. Conclusion: Present study indicated that berberine shows a protective role in diabetes-associated renal and cardiovascular complications

Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar rats

241-247Nephrotoxicity is a frequent and severe side effect of 5-fluorouracil (5-FU) chemotherapy which limits its use clinically regardless of being one of the most promising chemotherapeutic agents. Here, we assessed the nephroprotective activity of two structurally related phenolic acids 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) and gentisic acid (2,5 dihyroxybenzoic acid) against 5-FU induced nephrotoxicity in Wistar rats. Intraperitoneal administration of 5-FU at a dose of 20 mg/kg once a day for 5 days produced a significant elevation in serum parameters of the kidney such as uric acid, urea, creatinine, sodium and potassium levels along with severe histopathological changes in renal tissues of rats indicating severe nephrotoxicity. Administration of 2-pyrocatechuic acid (2-PCA) at 10, 30 and 100 by oral route for 9 days and additional 5 days with 5-FU resulted in an amelioration of altered serum parameters in a dose-dependent manner. Moreover, 2-PCA attenuated the renal damage produced by 5-FU demonstrating its efficacy as a nephroprotective agent for the prevention as well as amelioration of 5-FU induced nephrotoxicity. None of the doses of gentisic acid (GA) were found to be effective in this posology when given orally

Comparative studies on protective efficacy of gentisic acid and 2-pyrocatechuic acid against 5-fluorouracil induced nephrotoxicity in Wistar rats

Nephrotoxicity is a frequent and severe side effect of 5-fluorouracil (5-FU) chemotherapy which limits its use clinically regardless of being one of the most promising chemotherapeutic agents. Here, we assessed the nephroprotective activity of two structurally related phenolic acids 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) and gentisic acid (2,5 dihyroxybenzoic acid) against 5-FU induced nephrotoxicity in Wistar rats. Intraperitoneal administration of 5-FU at a dose of 20 mg/kg once a day for 5 days produced a significant elevation in serum parameters of the kidney such as uric acid, urea, creatinine, sodium and potassium levels along with severe histopathological changes in renal tissues of rats indicating severe nephrotoxicity. Administration of 2-pyrocatechuic acid (2-PCA) at 10, 30 and 100 by oral route for 9 days and additional 5 days with 5-FU resulted in an amelioration of altered serum parameters in a dose-dependent manner. Moreover, 2-PCA attenuated the renal damage produced by 5-FU demonstrating its efficacy as a nephroprotective agent for the prevention as well as amelioration of 5-FU induced nephrotoxicity. None of the doses of gentisic acid (GA) were found to be effective in this posology when given orally

Synthesis and antidiabetic evaluation of some novel compounds

849-854Aryloxypropanolmines have been reported to have β3-agonist activity. Agonists of β3-adrenergic receptors have been observed to simultaneously increase lipolysis, fat oxidation, energy expenditure and insulin action leading to the belief that this receptor might serve as an attractive target for the treatment of diabetes and obesity. Various aryloxypropanolamine derivatives have been synthesized starting with the substituted imines derived from 4-hydroxy benzaldehyde and substituted anilines. These imines have been converted to benzamide intermediates. The benzamide epoxide intermediates have been synthesized using epichlorhydrin. The title compounds 6a-j have been synthesized via ring opening of the epoxides. The synthesized compounds have been characterized using infrared (IR), nuclear magnetic resonance (NMR) and mass spectrometry. The synthesized compounds have been evaluated for antidiabetic activity on streptozotocin induced diabetic male Wistar rats. The synthesized aryloxypropanolamine derivative consisting of –OCH3 and t-butyl amine substituents show good activity as compared to the other synthesized compounds in the series. Glibenclamide has been taken as standard for measuring the antidiabetic activity