Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases.
Oleanolic acid (OA) is a natural triterpenoid, which has been used in Chinese medicine for the treatment of liver disorders for many years. Its pharmacological activities have been the focus of intense research in recent years. However, there is little research on the antioxidant activities of OA. In the present study, we aim to investigate whether OA produces its protective effects mainly through antioxidant mechanisms and whether OA plays as an antioxidant through quenching reactive oxygen species (ROS), inhibiting lipid peroxidation or stimulating cellular antioxidant defenses. In the in vitro antioxidant activity-assessing models, OA acted as not only a free radical-scavenger through direct chemical reactions but also a biological molecule, which may enhance the antioxidant defenses. tert-Butyl hydroperoxide (tBHP) induced ROS generation, damaged plasma membrane and decreased cell viability and the expression of key antioxidant enzymes and MAP kinases in QZG cells. OA ameliorated the oxidative injury induced by tBHP through increasing the generation of antioxidant (glutathione) and the expression of key antioxidant enzymes mediated by nuclear factorerythroid 2 p45-related factor 2 (Nrf2), in which process, activation of JNK and ERK, but not p38, was involved. The present study, for the first time, investigated the antioxidant activities of OA systematically. OA probably functions mainly through indirect biological effect and protects QZG cells against cytotoxicity induced by tBHP through increasing the generation of antioxidant and the expression of oxidative stress sensitive transcription factor-Nrf2, and MAP kinases, mainly JNK and ERK. These findings may significantly better the understanding of OA and advance therapeutic approaches to the diseases which are associated with oxidative stress.
Wang
Xin
X
Department of Toxicology, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China.
Ye
Xiao-long
XL
Liu
Rui
R
Chen
Hong-Li
HL
Bai
Hua
H
Liang
Xin
X
Zhang
Xiao-Di
XD
Wang
Zhao
Z
Li
Wen-li
WL
Hai
Chun-Xu
CX
D000818:Animals; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism* / Q000502:physiology; D009828:Oleanolic Acid / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid; D020122:tert-Butylhydroperoxide; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione