title: Inhibitory effects of capsaicin on hepatic stellate cells and liver fibrosis.
abstract: Hepatic stellate cells (HSCs) play an important role in the process of liver fibrosis. In this study, we investigated the inhibitory effects of capsaicin on HSCs and liver fibrosis. Cultured HSCs were incubated with various concentrations of capsaicin. Cell proliferation was examined using a cell counting kit. Production of hydrogen peroxide was determined using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay. The mRNA and protein expression of target genes was analyzed by reverse transcription PCR and Western blot analysis, respectively. Cell apoptosis was evaluated by annexin V-FITC and propidium iodide (PI) costaining followed by flow cytometric analysis. A CCl4 rat liver fibrosis model was used to assess in vivo effects of capsaicin by histological examination and measurement of liver fibrosis markers, including hydroxyproline content, serum type III collagen, and hyaluronic acid (HA) levels. Our results show that capsaicin dose-dependently inhibited cell proliferation, suppressed cell activation, and decreased hydrogen peroxide production in cultured HSCs. Capsaicin reduced the mRNA levels of tissue inhibitors of metalloproteinase 1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in HSCs. Moreover, capsaicin-induced cell apoptosis was associated with increased expression of Bax, cytochrome c (cyt c), and caspase-3, but reduced levels of Bcl-2. The animal studies further revealed that capsaicin efficiently reduced the extent of liver fibrosis, inhibited HSC proliferation, and promoted cell apoptosis. Our findings suggest that capsaicin might inhibit fibrogenesis by inhibiting the activities of HSCs.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, Zhejiang, China.
authors.forename: Fu-Xiang
authors.initials: FX
authors.lastname: Yu
authors.forename: Yin-Yan
authors.initials: YY
authors.lastname: Teng
authors.forename: Qian-Dong
authors.initials: QD
authors.lastname: Zhu
authors.forename: Qi-Yu
authors.initials: QY
authors.lastname: Zhang
authors.forename: Yin-He
authors.initials: YH
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024061:Collagen Type III / Q000097:blood; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006820:Hyaluronic Acid / Q000097:blood; D006861:Hydrogen Peroxide / Q000737:chemistry; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D024061:Collagen Type III; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide; D053148:Caspase 3; D006909:Hydroxyproline; D002211:Capsaicin
keywords: activation; apoptose; apoptosis; capsaicin; capsaïcine; cellules hépatiques stellaires; fibrose hépatique; hepatic stellate cells; liver fibrosis