title: Isolation and structural characterization of 2R, 3R taxifolin 3-O-rhamnoside from ethyl acetate extract of Hydnocarpus alpina and its hypoglycemic effect by attenuating hepatic key enzymes of glucose metabolism in streptozotocin-induced diabetic rats.
abstract: Hydnocarpus alpina Wt. (Flacourtiaceae) (H. alpina) is a large tree traditionally used to treat leprosy; it also posses antidiabetic property. The present study was undertaken to isolate, characterize and to evaluate the antidiabetic effect of 2R, 3R taxifolin 3-O-rhamnoside. (rhamnoside) and its impact on carbohydrate metabolic key enzymes in control and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). Oral administration of rhamnoside for 21 days significantly reduced food intake, calorie intake, blood glucose and glycosylated hemoglobin levels, and improved plasma insulin levels. Administration of rhamnoside showed significant increase in the body weight, body composition (Lean body weight (LBW) and retro body fat), glycolytic hexokinase, glucose-6-phophate dehydrogenase and pyruvate kinase levels where as significant decrease was observed in the levels of glucose-6-phosphatase fructose-1, 6-bisphosphatase and lactate dehydrogenase in diabetic treated rats. Further, administration of rhamnoside significantly improved the glycogen content, glycogen synthase and glycogen phosphorylase, suggesting the antihyperglycemic potential of rhamnoside in diabetic rats. The results obtained were compared with glibenclamide a standard hypoglycaemic drug. Immunohistopathological study of pancreas revealed increased number of β-cells and insulin granules in diabetes-induced rats after treatment with rhamnoside for 21 days. Furthermore, Co-administration of rhamnoside (50 mg/kg) with nifedipine (13.6 mg/kg), a Ca(2+)ion channel blocker, or nicorandil (6.8 mg/kg), an ATP-sensitive K(+) ion channel opener, reveals the insulin secretion property of rhamnoside via a K(+)-ATP channels dependent pathway in diabetic rats. In conclusion, rhamnoside normalized blood glucose, glycosylated hemoglobin, key hepatic enzymes and glycogen content by increasing insulin secretion via K(+)-ATP channels dependent signaling pathway. The results suggest that the rhamnoside from H. alpina could be used as a therapeutic agent to treat diabetes mellitus.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, 664-14, 1GA Deokjin-Dong, Deokjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea.
authors.forename: Rangachari
authors.initials: R
authors.lastname: Balamurugan
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, 600034, India.
authors.forename: Subramanian Ezhil
authors.initials: SE
authors.lastname: Vendan
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, 664-14, 1GA Deokjin-Dong, Deokjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea.
authors.forename: Adithan
authors.initials: A
authors.lastname: Aravinthan
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, 664-14, 1GA Deokjin-Dong, Deokjin-Gu, Jeonju City, Jeollabuk-Do 561-756, Republic of Korea. Electronic address: jhkim1@jbnu.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D005947:Glucose / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D010936:Plant Extracts / Q000737:chemistry*; D017208:Rats, Wistar
chemical_list: D000085:Acetates; D006027:Glycosides; D007004:Hypoglycemic Agents; D010936:Plant Extracts; C007650:ethyl acetate; D005947:Glucose
keywords: 2R, 3R taxifolin 3-O-rhamnoside; Ca(2+) channel; Diabetes mellitus; Hepatic enzymes; Hydnocarpus alpina; K(+) channel