The protective effect of Danning tablet against hepatic sinusoidal obstruction syndrome induced by Gynura Rhizoma

Recently, hepatic sinusoidal obstruction syndrome (HSOS) caused by Gynura Rhizoma (Tusanqi) has gained global attention. The purpose of this research is to investigate the effects and mechanisms of Danning tablet, a traditional Chinese formula, on protecting against HSOS induced by Gynura Rhizoma. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. HSOS was induced by intragastrical administration of Gynura Rhizoma extract (1 g·kg^-1·d^-1) for 40 consencutive days. On the other hand, mice in the protection group were intragastrical administration of Danning tablet powder (3 g·kg^-1·d^-1) 4 hours before treatment of Gynura Rhizoma extract. The results showed that Danning tablet could significantly attenuate the liver injury in HSOS mice. Mice in the protection group showed decreased serum activity of spartate amino transferase, and levels of total bile acids and total bilirubin. In addition, the endothelial damage to the central venules, subendothelial hemorrhage, sinusoidal hemorrhage, and subendothelial fibrosis in HSOS mice were clearly attenuated in the protection group. Measurements of the key factors involved in liver fibrosis revealed that protection group showed significantly reduction in hepatic hydroxyproline concentration, mRNA expression of α-smooth muscle actin and fibrosis-related genes such as Collagen-1, Collagen-3, Mmp2 and Mmp9, as well as Smad3 phosphorylation (p-Smad) and serum transforming growth factor-β (TGF-β). Moreover, pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, were also reversed in the protection group. All these results demonstrate the key roles of the TGF-β/p-Smad3 and inflammatory signaling pathways in the protection effect of Danning tablet on Gynura Rhizoma-induced HSOS, and pointing to the possibility of utilizing Danning tablet for protection against Gynura Rhizoma induced HSOS clinically.