Gamma-oryzanol protects human liver cell (L02) from hydrogen peroxide-induced oxidative damage through regulation of the MAPK/Nrf2 signaling pathways.

Abstract

Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be available and served as an antioxidant. The present study was to explore the potential protective effects of Orz on oxidative stress and cell apoptosis in human hepatic cells (L02 cells) induced by hydrogen peroxide (H2 O2 ). Flow cytometry detection and Hoechst 33258 staining showed that Orz significantly restored cell cycle and ameliorated apoptosis in H2 O2 -challenged L02 cells. Orz pretreatment inhibited H2 O2 -induced cell apoptosis by increasing the scavenging of hydroxyl radicals (OH·), and efficiently decreasing the production of nitric oxide (NO). Moreover, a loss of total antioxidant capacity (T-AOC) and adenosine triphosphatase (ATPase) were enhanced in H2 O2 -mediated L02 cells pretreated with Orz. Furthermore, preincubation with Orz reduced H2 O2 -mediated the proapoptotic protein of Bak expression and the phosphorylation of ASK1, p38, JNK, and ERK, and increased the anti-apoptotic protein of Bcl-xl expression and anti-oxidative stress proteins of Nrf2 and HO-1 expression. The findings suggested that Orz exerts the cytoprotective effects in H2 O2 -induced L02 cells apoptosis by ameliorating oxidative stress via inhibiting MAPK signaling pathway and activating Nrf2 signaling pathway. PRACTICAL APPLICATIONS: Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be availably served as an antioxidant. In this study, it was found that Orz exerts the cytoprotective effects in H2 O2 -induced L02 cell apoptosis by ameliorating oxidative stress via the inhibition of MAPK signaling pathway and the activation of Nrf2 signaling pathway, which provides a theoretical basis for dietary adding natural products to prevent or treat oxidative stress-related diseases.