Abstract：
BACKGROUND: 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.
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.
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.
摘要：
背景：肝纤维化（LF）是慢性肝损伤的常见可逆后果，治疗选择有限。银辰弓英汤（YGD）由两种同源植物组成：（蒿，蒲公英单衣原体手。-爵士.),传统上用作急性黄疸性肝炎的药用饮食。然而,其对LF和潜在机制的影响尚不清楚。
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。
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。
