Tanshinone IIA Ameliorates Nonalcoholic Steatohepatitis in Mice by Modulating Neutrophil Extracellular Traps and Hepatocyte Apoptosis

Abstract

Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is widely used in the treatment of a variety of diseases and syndromes. Tanshinone IIA (TIIA), a phenanthrenequinone-class derivative extracted from S. miltiorrhiza, is one of its main active components and has anti-inflammatory effects on various tissues and cells. This study aimed to investigate the beneficial effects of TIIA on nonalcoholic steatohepatitis (NASH) induced in mice using a methionine choline deficiency (MCD) diet and the underlying mechanism of these. Our results reveal that TIIA remarkably ameliorated hepatic steatosis and inflammation and decreased the serum levels of liver dysfunction markers while increasing the levels of serum total cholesterol and triglycerides in MCD-fed mice. TIIA significantly reduced mRNA levels of the inflammatory factors TNF-α, IL-6, and TGF-β. Similarly, TIIA inhibited caspase-3 and Bax-mediated apoptosis in MCD-fed mice. Together, our data indicate that TIIA inhibits the formation of MPO and CitH3 in neutrophil extracellular traps and inhibits apoptosis mediated by caspase-3 and Bax in hepatocytes, thereby mitigating inflammatory progression in an MCD diet-induced NASH mouse model.

Comparative efficacy of Chinese patent medicines for non-alcoholic fatty liver disease: A network meta-analysis

“…Saikosaponin-d, the extract of Bupleurum chinense, could inhibit the inflammatory reaction in NAFLD mice and achieve the liver protective effect ( Chang et al, 2021 ). Salvianolic acid B, Tanshinone IIA and Salvianolic acid A in Salvia miltiorrhiza extract could improve the inflammatory damage in NAFLD mice ( Li et al, 2020 ; Meng et al, 2022 ; Xu et al, 2022 ). Qianggan capsule had the best effect in reducing serum TG level.…”

Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms

“…By preventing the development of neutrophil extracellular traps linked to the production of MPO, TSO might diminish inflammatory TNF-α and IL-6 markers to control hepatocyte death in MCD diet-fed NASH mice. Overexpression of TGF-β was also reverted by TSO via SMAD signalling [180]. Furthermore, TSO minimised oxidative stress by reducing the formation of ROS and MDA while increasing the activities of SOD and GPx, which could also help to prevent cytotoxicity and improve HS [181].…”

Traditional Chinese medicines and natural products targeting immune cells in the treatment of metabolic-related fatty liver disease

“…MPO and CITH3 are two components of NETs that contribute to the pro-inflammatory response (Saisorn et al, 2021). TIIA has been shown to inhibit the formation of MPO and CITH3 in NETs, thereby reducing the inflammatory response in the liver (Xu et al, 2022). Caspase-3 and bax are two proteins involved in the apoptotic pathway in cells (Xu et al, 2022).…”

“…TIIA has been shown to inhibit the formation of MPO and CITH3 in NETs, thereby reducing the inflammatory response in the liver (Xu et al, 2022). Caspase-3 and bax are two proteins involved in the apoptotic pathway in cells (Xu et al, 2022). Inflammatory liver diseases often lead to hepatocyte apoptosis (Xu et al, 2022).…”

“…Caspase-3 and bax are two proteins involved in the apoptotic pathway in cells (Xu et al, 2022). Inflammatory liver diseases often lead to hepatocyte apoptosis (Xu et al, 2022). TIIA has been shown to inhibit caspase-3 and bax-mediated apoptosis of hepatocytes, thereby preventing liver damage and inflammation (Xu et al, 2022).…”