Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver.
Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations were conducted using t-BHP-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats to evaluate the antioxidative bioactivity of berberine. The results in rat primary hepatocytes demonstrated that berberine, at the concentrations of 0.01-1.0 mM, significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP (1.5 mM). Berberine also attenuated the t-BHP-induced depletion of glutathione (GSH) and induced a high level of DNA repair synthesis. The in vivo study showed that the intraperitoneal pretreatment with berberine (0.5 and 5 mg/kg) for 5 days before a single dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and aspartate aminotransferase) and reduced oxidative stress in the liver. The histopathological evaluation of the livers revealed that berberine reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltrations, and necrosis induced by t-BHP. These results lead us to speculate that berberine may play a chemopreventive role via reducing oxidative stress in living systems.
Hwang
Jin-Ming
JM
Department of Biochemistry, Medical College, Chung Shan Medical University, No. 110, Section 1, Chien Kuo N. Rd., Taichung 402, Taiwan.
Wang
Chau-Jong
CJ
Chou
Feu-Pi
FP
Tseng
Tsui-Hwa
TH
Hsieh
Yih-Shou
YS
Lin
Wea-Lung
WL
Chu
Chia-Yih
CY
D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D004249:DNA Damage; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D005609:Free Radicals; D017382:Reactive Oxygen Species; D001599:Berberine; D020122:tert-Butylhydroperoxide; D005978:Glutathione