Antidiabetic effect of oleanolic acid: a promising use of a traditional pharmacological agent.
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. Although the clear mechanisms of DM and insulin resistance are still to be cleared, it has been well documented that reactive oxygen species (ROS) play a pivotal role in DM and multiple types of insulin resistance. For the past few years, natural substances have been shown to have the potential to treatment DM. Attention has been especially focused on plants rich in triterpenoids, which generally show antioxidant and antiglycation effect. In our previous studies, it was shown that oleanolic acid (OA), a natural triterpenoid and an aglycone of many saponins, is a potent antioxidant acting as not only a free radical-scavenger through direct chemical reactions but also as a biological molecule, which may enhance the antioxidant defenses. The present study aimed to investigate the potential antidiabetic effect of OA. Oleanolic acid showed a significant blood glucose-lowering and weight-losing effect in diabetic animals induced by streptozotocin (STZ). In the insulin resistant model, it was also shown that OA may promote insulin signal transduction and inhibit oxidative stress-induced hepatic insulin resistance and gluconeogenesis, in which process the phosphorylation of ERK and the protective effect on mitochondrial function may be involved. These findings may significantly better the understanding of the pharmacological actions of OA and advance therapeutic approaches to DM.
Department of Toxicology, Faculty of Preventive Medicine, the Fourth Military Medical University, Xi'an 710032, China.
Xin
X
Wang
Yu-Liang
YL
Li
Hao
H
Wu
Jiang-Zheng
JZ
Liu
Jun-Xia
JX
Hu
Nai
N
Liao
Jie
J
Peng
Pei-Pei
PP
Cao
Xin
X
Liang
Chun-Xu
CX
Hai
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D053078:Membrane Potential, Mitochondrial; D009828:Oleanolic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid