title: Hypoglycemic action of borapetoside A from the plant Tinospora crispa in mice.
abstract: OBJECTIVE
  This study explores the hypoglycemic effects of borapetoside A, the most active principle among three major diterpenoids (borapetosides A, B, and C) isolated from ethanol extract of Tinospora crispa vines.
  
  
  METHODS
  We employed mouse mitogenic C2C12 and hepatocellular carcinoma Hep3B cells in this study. Furthermore, the mice were divided into three groups, including streptozotocin-induced type 1 diabetes mellitus, diet-induced type 2 diabetes mellitus, and normal control. The mice in each group were treated with assigned vehicle control, borapetoside A, or other active agents.
  
  
  RESULTS
  Borapetoside A was shown to increase the glycogen content and decrease the plasma glucose concentration in a concentration or dose-dependent manner in vitro and in vivo. The hypoglycemic effects in the normal mice and the mice with type 2 diabetes mellitus were associated with the increases of the plasma insulin levels; whereas, the insulin levels remained unchanged in the mice with type 1 diabetes mellitus. Borapetoside A not only attenuated the elevation of plasma glucose induced by an intraperitoneal glucose tolerance test, but also increased the glycogen synthesis of IL-6 treated C2C12 cells. Moreover, the elevated protein expression levels of phosphoenolpyruvate carboxykinase were reversed after borapetoside A treatment twice a day for 7 days.
  
  
  CONCLUSIONS
  The hypoglycemic effects of borapetoside A were mediated through both the insulin-dependent and the insulin-independent pathways. Furthermore, borapetoside A was shown to increase the glucose utilization in peripheral tissues, to reduce the hepatic gluconeogenesis, and to activate the insulin signaling pathway; they thereby contributed to the lowering of the plasma glucose. Comparison of the structures of three borapetosides suggests clearly that the C-8 stereochemistry plays a key role in hypoglycemic effect since the active borapetoside A and C possess 8R-chirality but the inactive borapetoside B possess 8S-chirality. The location of glycoside at C-3 for borapetoside A but C-6 for borapetoside C and the formation of lactone between C-4 and C-6 for borapetoside A, could account for the different potency in hypoglycemic action for these two compounds.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Tun
authors.initials: CT
authors.lastname: Ruan
authors.forename: Sio-Hong
authors.initials: SH
authors.lastname: Lam
authors.forename: Shoei-Sheng
authors.initials: SS
authors.lastname: Lee
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification; D010946:Plants, Medicinal / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D031610:Tinospora / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D004224:Diterpenes; D005960:Glucosides; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D010936:Plant Extracts; C585193:borapetoside A; D006003:Glycogen; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose