Induction of Nrf2 pathway by Dendrobium nobile Lindl. alkaloids protects against carbon tetrachloride induced acute liver injury

摘要

Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of Dendrobium, has been shown to possess antioxidative effects. The nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway plays a critical role in the cellular response to oxidative stress. Oxidative damage has been implicated in the mechanism of various hepatotoxins induced liver injury. The present study aimed to examine the protective effects of DNLA on CCl4-induced acute liver injury, and to explore the role of the Nrf2 pathway in the protective action of DNLA. Wild-type (WT) and Nrf2-knockout (Nrf2(-/-)) mice were administrated with DNLA (20 mg/kg/day, ig) for 7 days, and then challenged with CCl4 (20 mu L/kg, ip). In WT mice, DNLA reduced CCl4 induced liver injury, as evidenced by the reduction in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), attenuation of malondialdehyde (MDA) production, and improved ultrastructural morphology in hepatocytes. However, the protective effect was diminished in Nrf2(-/-) mice, indicating an essential role of Nrf2 in DNLA-mediated protection over CCl4 liver injury. Furthermore, it was found that DNLA enhanced Nrf2 expression and nuclear accumulation and increased the expression of Nrf2 regulated downstream proteins. These results demonstrate that DNLA protects mice from CCl4 induced liver injury, probably through the activation of the Nrf2 signaling pathway.