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

Baoying Wang,Yunlian Hu,Zhang’E Xiong,Erping Xu,Zhenqiang Zhang,Xiaolin Gao,Yucheng Li,Ming Bai,Baoguang Liu

doi:10.29219/fnr.v63.3567

Abstract

BackgroundCurcumin 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.ObjectiveThe present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism.DesignAlcohol-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, Ca2+-ATPase, and Ca2+Mg2+-ATPase, were determined. The level of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening was also determined. The expression of PGC-1α, NRF1, Mn-SOD, GRP78, PERK, IRE1α, nuclear NF-κB, and phosphorylated IκBα was quantified by western blot. The contents of TNF-α, IL-1β, and IL-6 in the liver were measured using the ELISA method.ResultsCurcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP, thus increasing the MMP, promoting the activity of Na+/k+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase, and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1α, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1α in hepatic tissue. Curcumin also attenuated inflammation by inhibiting the IκBα–NF-κB pathway, which reduced the production of TNF, IL-1β, and IL-6.ConclusionCurcumin 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.

Highlights

Curcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa
Curcumin improved the alcohol-induced liver histopathology in mice As shown in Fig. 1, in normal control group and curcumin control group, the structure of the hepatocyte cord was intact, hepatocyte cytoplasm was evenly distributed, and no fat vacuoles and inflammatory cells infiltrations were found (Fig. 1a and b); in the model group, the hepatocytes were swollen, the cytoplasm distributed loosely, and fat vacuoles and inflammatory cells were observed (Fig. 1c); compared with the model group, hepatocyte swelling and cytoplasm looseness were alleviated in curcumin-administered groups, and no fat vacuoles were observed (Fig. 1d and e)
Curcumin alleviated the decrease of liver membrane potential (MMP) in mice with chronic alcoholic liver injury The fresh liver mitochondria were incubated with the fluorescent dye Rhodamine 123 (Rh123), and the fluorescence intensity was measured by a fluorescence spectrophotometer

Summary

Introduction

Curcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa. Objective: The present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism. The activities of mitochondrial antioxidant enzymes, Na+/k+-ATPase, Ca2+-ATPase, and Ca2+Mg2+-ATPase, were determined. Results: Curcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP, increasing the MMP, promoting the activity of Na+/k+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase, and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1α, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1α in hepatic tissue. Curcumin attenuated inflammation by inhibiting the IκBα–NF-κB pathway, which reduced the production of TNF, IL-1β, 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

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