Protective effects of curcumin against chronic alcohol-induced liver injury in mice through modulating mitochondrial dysfunction and inhibiting endoplasmic reticulum stress

Background: Curcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa. In Ayurveda and traditional Chinese medicine, it has been used as a hepatoprotective agent for centuries. however, the underlying mechanisms are not clear. Objective: The present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism. Design: Alcohol-exposed Balb/c mice were treated with curcumin (75 and 150 mg/kg) once per day for 8 weeks. Tissue from individual was fixed with formaldehyde for pathological examination. The activities of mitochondrial antioxidant enzymes, Na+/k+-ATPase, Ca-2(+)-ATPase, and (Ca+Mg2+)-Mg-2-ATPase, were determined. The level of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP)opening was also determined. The expression of PGC-1 alpha, NRF1, Mn-SOD, GRP78, PERK, IRE1 alpha, nuclearNF-kappa B, and phosphorylated I kappa B alpha was quantified by western blot. The contents of TNF-alpha, IL-1 beta, and IL-6 in the liver were measured using the ELISA method. Results: Curcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP,thus increasing the MMP, promoting the activity of Na+/k(+)-ATPase, Ca-2(+)-ATPase, and Ca-2(+)/Mg-2(+)-ATPase,and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1 alpha, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1 alpha in hepatic tissue. Curcumin also attenuated inflammation by inhibiting the I kappa B alpha-NF-kappa B pathway, which reduced the production of TNF, IL-1 beta, and IL-6. Conclusion Curcumin attenuates alcohol-induced liver injury via improving mitochondrial function and attenuating endoplasmic reticulum stress and inflammation. This study provides strong evidence for the beneficial effects of curcumin in the treatment of chronic alcohol-induced liver injury.