Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation
Xiangming Tao, Dong Li, Chong Zhang, Guang-Hua Wen, Chao Wu, Yuanyuan Xu, Yue Kan, Wanpeng Lu, Hanyan Ding, Yan Yang
Abstract
Salvianolic acid B (Sal B) has strong antioxidant and anti-fibrosis effects, which are related to the transforming growth factor β/Smad signaling pathway. However, how Sal B affects this antioxidant pathway and the phosphorylation (p-) of Smad2 at both the COOH-terminal (pSmad2C) and linker region (pSmad2L) are unknown. The aims of the present study were to investigate the underlying mechanisms of Sal B on acute and chronic liver injury induced by CCl<sub>4</sub> and H<sub>2</sub>O<sub>2</sub>, and its effects on p-Smad2C/L. In <em>in vivo</em> experiments, acute and chronic liver injury models were induced by CCl<sub>4</sub>, and the oxidative damage cell model was established <em>in vitro</em> with H<sub>2</sub>O<sub>2</sub>. Liver histopathology was assessed using hematoxylin and eosin and Van Gieson's staining. Moreover, serum biochemical indicators were analyzed using specific assay kits. Furthermore, the present study evaluated the oxidant/antioxidant status in acute and chronic liver injury models by oxidative stress parameters such as malondialdehyde, glutathione and superoxide dismutase. In addition, western blot analysis was performed to analyze the protein expression levels of pSmad2C, pSmad2L, nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). It was found that Sal B improved liver histology, decreased the levels of aminotransferase and attenuated oxidative stress in acute and chronic liver injury models. Additionally, the protein expression levels of pSmad2C and pSmad2L were decreased, but Nrf2 and HO-1 expression levels were increased both <em>in vivo</em> and <em>in vitro</em>. Collectively, the present results suggested that Sal B may protect against acute and chronic liver injury via inhibition of Smad2C/L phosphorylation, and the Nrf2/HO-1 signaling pathway may play an important role in this process.