Abstract
Objective:Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases.Chuanxiong Rhizoma(Chuanxiong in Chinese,CX)is a traditional Chinese herbal product to prevent cerebrovascular,gynecologic and hepatic diseases.Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells(HSCs).Here,this study aimed to compare the protection of different CX extracts on bile duct ligation(BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.Methods:The active compounds of CX extracts were identified by high performance liquid chromatogra-phy(HPLC).Network pharmacology was used to determine potential targets of CX against hepatic fibro-sis.Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation.The expression of targets of interest was determined by quantitative real-time PCR(qPCR)and Western blot.Results:Different CX extracts were identified by tetramethylpyrazine,ferulic acid and senkyunolide A.Based on the network pharmacological analysis,42 overlap targets were obtained via merging the can-didates targets of CX and liver fibrosis.Different aqueous,alkaloid and phthalide extracts of CX(CXAE,CXAL and CXPHL)significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor(CTCF)-c-MYC-long non-coding RNA H19(H1 9)pathway in the BDL-induced mouse model.Meanwhile,CX extracts,especially CXAL and CXPHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with tauro-cholate acid(TCA),lithocholic acid(LCA)and transforming growth factor beta(TGF-β),as illustrated by decreased bile duct proliferation markers.Conclusion:Our data supported that different CX extracts,especially CXAL and CXPHL significantly allevi-ated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway,providing novel insights into the anti-fibrotic mechanism of CX.
基金项目
Beijing Municipal Science &Technology Commission(7212174)
National High-Level Talents Special Support Program()
National Key Research and Development Program on Modernization of Traditional Chinese Medicine(2022YFC3502100)
National Natural Science Foundation of China(82004045)
National Natural Science Foundation of China(82274186)
NETL
NSTL
万方数据