Protective effects of oleanolic acid on cerebral ischemic damage in vivo and H(2)O(2)-induced injury in vitro.
BACKGROUND
Oleanolic acid (OA), a triterpenoid compound, exists in many plants. It has numerous bioactivities and has been used to treat hepatitis in China. However, few studies have reported its effect on the central nervous system, especially in ischemic stroke.


OBJECTIVE
To explore the protective effects of OA on cerebral ischemic injury for the first time.


METHODS
Survival time was tested in mice injured by bilateral common carotid artery ligation (BCCAL). Neurological function, infarct area, cerebral edema, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were estimated in rats operated by middle cerebral artery occlusion (MCAO). Cell survival, lactate dehydrogenase (LDH), SOD, reduced glutathione (GSH), MDA, mitochondrial membrane potential (MMP) and succinic dehydrogenase (SDH) were detected in H(2)O(2)-injured PC12 cells.


RESULTS
Pre-administration with OA significantly prolonged survival time in mice at 50 and 25 mg/kg, alleviated neurological function, infarct area and cerebral edema, increased SOD and GSH-Px activities and decreased MDA level in rats at 25 and 12.5 mg/kg. Pre-treatment with OA at 10 and 1 μM remarkably improved cell survival, enhanced SOD activity and GSH content, reduced LDH and MDA levels and reversed the lowering of MMP and SDH activity.


CONCLUSIONS
These results demonstrate that oleanolic acid effectively alleviates cerebral ischemic damage in vivo and oxidative injury in vitro, which may be in part due to the modulation of endogenous antioxidants and the improvement of mitochondrial function. Oleanolic acid may be a potential medicine for attenuating ischemic stroke.
Rong
Zhi-Tao
ZT
Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Gong
Xiao-Jian
XJ
Sun
Hong-Bin
HB
Li
Yun-Man
YM
Ji
Hui
H
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy*; D015996:Survival Rate
D000975:Antioxidants; D009828:Oleanolic Acid; D006861:Hydrogen Peroxide