Salvianolic acid B protects against acute and chronic liver injury by inhibiting Smad2C/L phosphorylation

Autor: Yan Yang, Yuan-Yuan Xu, Chao Wu, Wanpeng Lu, Xiang-Ming Tao, Hanyan Ding, Yue Kan, Dong Li, Chong Zhang, Guanghua Wen
Rok vydání: 2021
Předmět:
Zdroj: Experimental and Therapeutic Medicine
ISSN: 1792-1015
1792-0981
DOI: 10.3892/etm.2021.9772
Popis: 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 CCl4 and H2O2, and its effects on p-Smad2C/L. In in vivo experiments, acute and chronic liver injury models were induced by CCl4, and the oxidative damage cell model was established in vitro with H2O2. 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 in vivo and in vitro. 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.
Databáze: OpenAIRE