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.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact

“…A number of these agents, including curcumin, emodin and matrine, have been shown to exert antifibrotic activity (27,28). Thus, these agents are of potential therapeutic value in the treatment of fibrosis of pulmonary silicosis.…”

The expression dynamics of transforming growth factor-β/Smad signaling in the liver fibrosis experimentally caused by Clonorchis sinensis

“…Biological functions of TGF-β and its roles in regulating ECM deposition have been intensively reviewed, and proteins of the Smads family members are important mediators that transduce signals induced by TGF-β to specific target genes in the nucleus, leading to the expression of pro-fibrotic genes [ 28 , 29 ]. There were also some studies suggesting that TGF-β 1 and its downstream Smads played a central role in parasite-induced liver fibrosis [ 20 , 30 , 31 ], for example, in Schistosoma mansoni -infected mouse, the increased expression of TGF-β 1 and its receptors led to extensive accumulation of extracellular matrix proteins and treatment with anti-fibrotic drugs like praziquantel can reduce the concentration of TGF-β signicantly and led to an reversible liver fibrosis in S. mansoni -infected mice [ 32 , 33 ].…”

The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress

“…In an alcohol-induced hepatic fibrosis animal model, curcumin has been demonstrated to play a hepatoprotective role in prevention of fibrosis development. It also inhibits cells proliferation and promotes cell death through ER stress activation and TGF- β /Smad signaling attenuation [ 127 ]. Nicotine has been reported to lose body weight through decreasing feeding and increasing thermogenesis of brown adipose tissue.…”