Effect of Atractylenolide Ⅲ on liver fibrosis in rats with non-alcoholic fatty liver disease by regulating the Hippo/YAP signaling pathway
YAO Shuo
LI Yuan
DUAN Chao
Abstract：Objective To investigate the effect of Atractylenolide Ⅲ(ATL Ⅲ)on liver fibrosis in rats with non-alcoholic fatty liver disease(NAFLD)by regulating the Hippo/yes-associated protein(YAP)signaling pathway.Methods Sprague-Dawley(SD)rats in the specific-pathogen free(SPF)grade were randomly grouped into control group,NAFLD group,low-dose ATL Ⅲ group,medium-dose ATL Ⅲ group,high-dose ATL Ⅲ group,and positive control group(Compound Biejia Ruangan tablets)using a random number table.Except for rats in the control group,NAFLD modeling was constructed by feeding a high-fat diet in the remaining rats.Drugs were administered by gavage or tail vein injection once a day for 4 consecutive weeks.Blood lipids and liver function indicators(alanine aminotransferase[AST]and aspartate aminotransferase[ALT])were detected.Serum levels of fibrosis indicators like hyaluronic acid(HA)and laminin(LN)were measured by Enzyme-linked immunosorbent assay(ELISA).Hematoxylin and eosin(H&E)staining was applied to observe pathological changes in rat liver tissues and the NAFLD activity score(NAS)was calculated.Masson staining was applied to observe liver fibrosis.Positive expression of α-smooth muscle actin(α-SMA)was detected by immunohistochemical staining.Western blot was applied to detect protein expressions of transforming growth factor-β1(TGF-β1)and proteins in the Hippo-YAP signaling pathway in rat liver tissue.Results Compared with those of the control group,rats in the NAFLD group presented significantly higher total cholesterol(TC),triglyceride(TG),low-density lipoprotein-cholesterol(LDL-C),HA,LN,AST,ALT,NAS and expression levels of α-SMA,TGF-β1 and transcriptional co-activator with PDZ-binding motif(TAZ),but significantly lower high-density lipoprotein-cholesterol(HDL-C),p-LATS1/LATS1 and p-YAP/YAP(P＜0.05).Compared with rats in the NAFLD group,rats in the low-dose ATL Ⅲ group,medium-dose ATL Ⅲ group,high-dose ATL Ⅲ group and positive control group presented significantly lower TC,TG,LDL-C,HA,LN,AST,ALT,NAS and expression levels ofα-SMA,TGF-β1 and TAZ,but significantly higher HDL-C,p-LATS1/LATS1 and p-YAP/YAP(P＜0.05).Conclusion ATL Ⅲ relieves liver fibrosis in NAFLD rats by inhibiting the activation of the Hippo/YAP signaling pathway.
Keywords：Atractylenolide ⅢHippo/yes-associated proteinnon alcoholic fatty liver diseaseliver fibrosis
Publication Date：2024-11-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 3212-3216,3221 )