OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
目的:本研究旨在评估YGD对四氯化碳(CCl4)诱导的肝纤维化的影响,并阐明其可能的机制。该研究旨在为YGD作为肝纤维化的候选药物奠定实验基础。
方法:LC-MS/MS鉴定了YGD中的11种血液进入成分,和网络药理学预测他们参与FoxO信号通路,胰岛素抵抗,和PI3K-AKT信号通路。使用CCl4诱导的LF小鼠模型,与阳性对照和正常组比较,评价YGD的保护作用。通过评估肝星状细胞(HSC)的激活,探讨了潜在的机制,纤维化信号,和炎症。
结果:YGD治疗显著改善肝功能,肝脏形态学增强,CCl4诱导的LF小鼠肝脏胶原沉积减少。机械上,YGD抑制HSC激活,MMPs/TIMP1比值升高,抑制FoxO1/TGF-β1/Smad2/3和YAP途径,并表现出抗炎和抗氧化作用。值得注意的是,YGD改善了胰岛素信号通路。
结论:YGD通过调节纤维化和炎症途径减轻小鼠的LF,增强抗氧化反应,并特异性抑制FoxO1/TGF-β1/Smad2/3和YAP信号通路。