RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND 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-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.
Assuntos
Artemisia , Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Cromatografia Líquida , Fosfatidilinositol 3-Quinases/metabolismo , Células Estreladas do Fígado , Espectrometria de Massas em Tandem , Fígado , Transdução de Sinais , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Tetracloreto de Carbono/farmacologiaRESUMO
OBJECTIVE: To explore the effect and mechanism of flavones of buckwheat flower and leaf (FBFL) on lowering blood glucose and improving insulin resistance in type 2 diabetic rats. METHOD: Seventy healthy male Wistar rats were used in this trial. Ten of them were selected randomly as normal group; the others were given fat milk by intragastric administration daily, from the 14th day on, low dose tetraoxypyrimidine was added by intraperitoneal injection every other day for three times. Rats with fasting (72 hours after the last injection) blood sugar > or = 16.7 mmol x L(-1) and K(IPT) < 60% of normal group were selected as type 2 diabetic model with insulin resistance, which were randomly divided into 5 groups: model group. LGLT group; low, moderate and high dosage FBFL groups (L-FBFL; M-FBFL; H-FBFL). Every rat was treated accordingly for 4 weeks; then FBG, FFA, INS were detected and ISI was calculated to evaluate the degree of insulin resistance. Liver PTP1B expression was determined by immunohistochemistry method. staining were observed by light microscopy. RESULT: FBFL could dose-dependently inhibit the rising of FBG, FFA, INS, improve the state of insulin resistance and reduce the expression level of liver PTP1B. CONCLUSION: FBFL could effectively improve insulin resistance in type 2 diabetic rats induced by tetraoxypyrimidine and fat milk and showed dose-dependence relationship.