Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-β1/ Smad2/3 and YAP signaling pathways

• Published in: Journal of ethnopharmacology 2024-06, Vol.327, p.117975-117975, Article 117975
• Main Authors: Feng, Xinyi, Liu, Hengxu, Sheng, Yifei, Li, Jiaqi, Guo, Jiyuan, Song, Wenxuan, Li, Sha, Liu, Zixuan, Zhou, Haoyu, Wu, Naijun, Wang, Rui, Chu, Jinxiu, Han, Xiaolei, Hu, Baofeng, Qi, Yajuan
• Format: Article
• Language: English
• Subjects: Insulin signaling pathway; Liver fibrosis; TGF-β1; YAP; Yinchen gongying decoction
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2024.117975

Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-β1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-β1/Smad2/3 and YAP signal pathways. [Display omitted]