Journal of Agricultural and Food Chemistry · 2016 · 78 citations · 31 references
Veterinary MedicineMedicinal ChemistryPharmacologyHepatotoxicologyInflammationMolecular PharmacologyAntifibrotic TherapyFibrosisHepatic FibrosisHepatic PathophysiologyHepatotoxicity MechanismsLiver DiseaseActivated Hepatic Stellate CellsCollagen Type I DepositionHepatic Stellate Cell BiologyHepatic Stellate Cell FunctionLiver Fibrosis ProgressionLiver Stellate Cell ActivationNf-κb SignalingSmad Signaling Pathway
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.
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A Vitamin D Receptor/SMAD Genomic Circuit Gates Hepatic Fibrotic Response
Ning Ding, Ruth T. Yu, Nanthakumar Subramaniam et al. · Cell · 2013 · 620 citations · Full text