title: Suppression of the TGF-β/Smad signaling pathway and inhibition of hepatic stellate cell proliferation play a role in the hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis.
abstract: The hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis have rarely been discussed and its mechanisms of action in alcohol-induced liver disease remain unknown. In this study, serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess hepatic function; histopathological and immunohistochemical observations were used to evaluate pathological and specific molecular changes in liver tissue and flow cytometry was used to detect the apoptosis in cultured hepatic stellate cells (HSCs), the major fibrogenic cells in the liver; PCR and western blot analysis were employed to evaluate the changes in the expression of molecules and signaling pathways. We demonstrate that curcumin alleviates alcohol-induced hepatic fibrosis by affecting the HSCs. We found that the administration of curcumin inhibited alcohol-induced HSC proliferation and even induced HSC apoptosis by stimulating endoplasmic reticulum (ER) stress. We also found that by suppressing the transforming growth factor-β (TGF-β)/Smad signaling pathway, the administration of curcumin impaired the production of extracellular matrix proteins in alcohol-stimulated HSCs. These results indicate that curcumin exerts its hepatoprotective effects against alcohol-induced hepatic fibrosis by inhibiting the proliferation and inducing the apoptosis of HSCs by stimulating ER stress and deactivating HSCs by suppressing the TGF-β/Smad signaling pathway.
authors: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Nanzheng
authors: N
authors: Chen
authors: Department of Nuclear Medicine, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Qianqian
authors: Q
authors: Geng
authors: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Jianbao
authors: J
authors: Zheng
authors: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Sai
authors: S
authors: He
authors: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Xiongwei
authors: X
authors: Huo
authors: Department of General Surgery, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Xuejun
authors: X
authors: Sun
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D000431:Ethanol; D005353:Fibronectins / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D020011:Protective Agents; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D000431:Ethanol; D003474:Curcumin