title: Capsaicin Inhibits Dimethylnitrosamine-Induced Hepatic Fibrosis by Inhibiting the TGF-β1/Smad Pathway via Peroxisome Proliferator-Activated Receptor Gamma Activation.
abstract: Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2.3 ± 0.1 to 1.0 ± 0.1) and Smad2/3 phosphorylation (from 1.5 ± 0.1 to 1.1 ± 0.1 and from 1.6 ± 0.1 to 1.1 ± 0.1, respectively) by activating Smad7 expression (from 0.1 ± 0.0 to 0.9 ± 0.1) via PPAR-γ induction (from 0.2 ± 0.0 to 0.8 ± 0.0) (p < 0.05). Furthermore, in HSCs, CPS inhibited the TGF-β1-induced increases in α-SMA and collagen type I expression, via PPAR-γ activation. These results indicate that CPS can ameliorate hepatic fibrosis by inhibiting the TGF-β1/Smad pathway via PPAR-γ activation.
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Jin
authors.affiliation: Jeollanamdo Institute of Natural Resources Research , Jeollanamdo, Republic of Korea.
authors.forename: Chul Yung
authors.initials: CY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Gi Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Yong An
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Department of Food Science, International University of Korea , Jinju, Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Chungnam National University , Daejeon, Republic of Korea.
authors.forename: Hye Gwang
authors.identifier: http://orcid.org/0000-0002-8020-8914
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D024042:Collagen Type I / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D051785:Smad Proteins / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D002211:Capsaicin; D024042:Collagen Type I; D004128:Dimethylnitrosamine; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D047495:PPAR gamma; D051785:Smad Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat
keywords: PPAR-γ; capsaicin; dimethylnitrosamine; hepatic stellate cells; liver fibrosis