Protective Effect and Mechanism of Xiaohuang Qudan Decoction on Liver Fibrosis by Regulating Autophagy
CHEN Lifeng
ZHANG Yujie
XIA Hao
WANG Dang
Abstract：Objective To investigate the protective effects of Xiaohuang Qudan Decoction on liver fibrosis and ex-plore its potential mechanisms.Methods A total of 18 specific pathogen free(SPF)-grade mice were randomly divided into control group,model group,high-dose traditional Chinese medicine group,medium-dose traditional Chinese medicine group,low-dose traditional Chinese medicine group and colchicine group(positive control),with 3 mice in each.Except for the control group,all the other groups were intraperitoneally injected with 10％CCl4 olive oil solution to establish mouse liver fibrosis model.The contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)and hydroxyproline(HYP)in serum were meas-ured;hematoxylin-eosin(HE)staining and Masson staining were used to observe liver pathological morphology and colla-gen deposition,while oil red O staining was used to observe lipid deposition in liver tissues;enzyme-linked immunosor-bent assay(ELISA)was used to detect levels of hyaluronic acid(HA),laminin(LN),type Ⅲ procollagen(PC Ⅲ)and type Ⅳ collagen(Col Ⅳ);immunohistochemistry was used to observe the levels of smooth muscle actin alpha(α-SMA),type Ⅰ collagen(ColⅠ)and transforming growth factor beta 1(TGF-β1)in liver tissues;real-time quantitative polymer-ase chain reaction(qPCR)was used to detect the gene expression levels of protein P62,autophagy-related gene Beclin 1,microtubule-associated protein light chain 3 Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),AMP-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR)and Unc-5 1 like autophagy activating kinase 1(ULK1)gene expression in liver tissues;Western blot was used to detect the protein expression levels of P62,Beclin-1,LC3-Ⅱ/Ⅰ,p-AMPK,AMPK,p-mTOR,mTOR and ULK1 in liver tissues.Results Compared with the control group,the contents of AST,ALT,HYP,LN,HA,PC Ⅲ and Col Ⅳ in the model group,low-dose Chinese medicine group,medium-dose Chinese medicine group,high-dose Chinese medicine group and the colchicine group significantly increased(P＜0.05).The expression lev-els of Beclin-1 and LC3-Ⅱ/Ⅰ proteins increased(P＜0.05),the expression levels of Beclin-1 and LC3 genes increased(P＜0.01),the expression levels of P62 protein and gene decreased(P＜0.01),the ratio of p-AMPK/AMPK and ULK1 protein and the expression of AMPK and ULK1 gene significantly increased(P＜0.05),while the expression of p-mTOR/mTOR protein and mTOR gene significantly decreased(P＜0.05).Compared with the model group,the con-tents of AST,ALT,HYP,LN,HA,PC Ⅲ and Col Ⅳ in the the low-dose Chinese medicine group,high-dose Chinese medicine group and the colchicine group decreased(P＜0.05),and the inflammatory infiltration and collagen deposition in the liver were significantly improved,and the liver fat deposition was improved;the protein expression of Beclin-1 and LC3-Ⅱ/Ⅰ decreased(P＜0.05),and the gene expression of Beclin-1 and LC3 decreased(P＜0.05),and the protein and gene expression of P62 increased(P＜0.05);the protein expression of α-SMA,Col Ⅰ and TGF-β1 significantly de-creased;the expression of p-AMPK/AMPK,UKL1 protein and AMPK gene significantly decreased(P＜0.05),and the expression of p-mTOR/mTOR protein and mTOR gene significantly increased(P＜0.05).Conclusion Xiaohuang Qudan Decoction can alleviate liver fibrosis to some extent,and its mechanism may involve regulating the AMPK/mTOR/ULK1 signaling pathway,reducing hepatic cell autophagy and thereby delaying the progression of liver fibrosis.
Keywords：Xiaohuang Qudan DecoctionLiver fibrosisAutophagyHepatic stellate cellsAMP-activated pro-tein kinas/mammalian target of rapamycin/Unc-51 like autophagy activating kinase 1 signaling pathway
Publication Date：2025-10-28
Online Publishing Date：2025-12-05(First online date of this platform, not the publication date of the document)
Pages：8( 845-852 )