TY - JOUR
T1 - Hypoglycemic action of borapetoside A from the plant Tinospora crispa in mice
AU - Ruan, Chi Tun
AU - Lam, Sio Hong
AU - Lee, Shoei Sheng
AU - Su, Ming Jai
N1 - Funding Information:
This work was supported by the Ministry of Economics and the National Science Council, Taiwan, Republic of China , under NSC-101-2325-B-002-058 , respectively. We thank Professor DK Granner (Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA) for the supply of antibodies specific to PEPCK.
PY - 2013/6/15
Y1 - 2013/6/15
N2 - Aim: 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.
AB - Aim: 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.
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U2 - 10.1016/j.phymed.2013.02.009
DO - 10.1016/j.phymed.2013.02.009
M3 - Article
C2 - 23523259
AN - SCOPUS:84878111064
SN - 0944-7113
VL - 20
SP - 667
EP - 675
JO - Phytomedicine
JF - Phytomedicine
IS - 8-9
ER -