Clerodane Diterpenoids with Anti-hyperglycemic Activity from Tinospora crispa.

Yuan Gao,Yin-Dong Fang,Ping Hai,Fei Wang,Yan-Fen Niu,Wen-Yong Xiong,Fang Wang,Ji-Kai Liu

doi:10.1007/s13659-016-0109-3

Abstract

Four new clerodane diterpenoids, tinosporols A–C (2–4) and tinosporoside A (5), together with six known analogues were isolated from the vines of Tinospora crispa. Their structures were established by extensive spectroscopic analysis. The relative configuration at C-12 in the known diterpenoid borapetoside E (1), the major component of the plant, was firstly established with the aid of molecular model. Compound 1 significantly reduced serum glucose levels at dose-dependent manners in alloxan-induced hyperglycemic mice and db/db type 2 diabetic mice.Graphical Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-016-0109-3) contains supplementary material, which is available to authorized users.

Highlights

Four new clerodane diterpenoids, tinosporols A–C (2–4) and tinosporoside A (5), together with six known analogues were isolated from the vines of Tinospora crispa
This plant is a prolific source of anti-hyperglycemic clerodane diterpenoids, among which borapetoside C was found to be an effective agent for the treatment of type 2 diabetes mellitus (T2DM) [2, 3]
As part of a BioBioPha [http://www.chemlib.cn] objective to assemble a large-scale natural products library valuable in the discovery of new drug leads from Traditional Chinese medicines (TCMs) [9,10,11], phytochemical investigation on the vines of T. crispa led to the isolation of four new clerodane diterpenoids, tinosporols A–C (2–4) and tinosporoside A (5), together with six known analogues

Summary

Graphical Abstract

Tinospora crispa (Menispermaceae) is a defoliation vine mainly distributed in Cambodia, India, Indonesia, Laos, Malaysia, Myanmar, Philippines, Thailand, and South China [1]. This plant is a prolific source of anti-hyperglycemic clerodane diterpenoids, among which borapetoside C was found to be an effective agent for the treatment of type 2 diabetes mellitus (T2DM) [2, 3]. The estimated prevalence of diabetes among a representative sample of Chinese adults was 11.6 % [5] Numerous drugs, such as rosiglitazone (ROS) and metformin (MET), have been used in the treatment of T2DM. The following describes the isolation and structural elucidation of compounds 1–5, and the antihyperglycemic activity of borapetoside E

Results and Discussion

H H-11 p ro-R*

General Experimental Procedures

Plant Material

Extraction and Isolation

Anti-hyperglycemia Activity