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Highlights: [•] An intermolecular interaction existed between CAPE and Trolox. [•] CAPE and Trolox exerted synergistic antioxidant effects by scavenging ROS directly. [•] CAPE and Trolox exerted synergistic antioxidant effects by inhibiting lipid peroxidation. [•] CAPE used with Trolox promoted the redox cycle of GSH mediated by Nrf2 in cells. [Copyright &y& Elsevier]

Alcoholic liver disease (ALD) is one of the leading causes of death in the world. Oxidative stress plays an important role in the pathogenesis of alcohol-induced liver injury. Our previous results have found that oleanolic acid (OA), a liver protective agent, plays a potent antioxidant activity in hepatocyte. In the present study, the protective effects of OA co-administration on ethanol-induced oxidative injury in rats were investigated through detecting hepatic histopathology, antioxidant enzymes, ethanol metabolic enzymes and inflammatory factors. Preventions of ethanol-induced oxidative injury by OA were reflected by markedly decreased serum activities of AST, ALT and significantly increased the hepatic ATP level. In addition, the increase of the hepatic TG content, MDA level and the decrease of hepatic GSH level, SOD activity, CAT activity induced by ethanol were significantly inhibited by OA co-administration. Furthermore, OA could also elevate the protein expressions and nuclear translocation of antioxidant transcription factor Nrf-2 and then up-regulated antioxidant enzymes expressions of HO-1, SOD-1 and GR. Moreover, OA co-administration can significantly reduce the activity and expressions of CYP2E1 and ADH, which has characteristic of generation ROS mediated oxidative stress and acetaldehyde respectively. Furthermore, OA co-administration could inhibition of the generation of inflammatory factors TNF-α and IL-6. Those above results indicated that OA co-administration can protect rats against ethanol-induced liver injury by induction Nrf-2 related antioxidant to maintain redox balance and modulating the ethanol-metabolizing and inflammatory pathway. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]