Curcumin ameliorates inflammatory reaction and oxidative
stress through activation of autophagy in experimental non-alcoholic fatty
liver disease rats

doi:10.3969/j.issn.2095-4344.2505

Abstract

Abstract:

BACKGROUND: Autophagy, oxidative stress and inflammatory reactions play an important role in non-alcoholic fatty liver disease. Curcumin has biological activities such as regulating autophagy, oxidative stress and inflammatory reaction.

OBJECTIVE: To explore the effect and underlying mechanism of curcumin on experimental non-alcoholic fatty liver disease rats.

METHODS: Non-alcoholic fatty liver model was established in rats fed 8-week high-fat diets. Forty healthy SPF male Sprague-Dawley rats were randomly divided into control group, model group, curcumin treatment group, and curcumin and 3-methyladenine (3-MA, an autophagic flux blocker) treatment group. At the end of 8 weeks of high-fat diet, control and model groups were given PBS intragastrically, curcumin treatment group given curcumin 500 mg/kg per day intragastrically, and curcumin+3-MA given curcumin 500 mg/kg per day intragastrically and 3-MA 2 mg/kg per day intraperitoneally. The interventions in each group were given for 8 continuous weeks. The biochemical parameters including serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, total cholesterol, fasting blood glucose level were measured in rats. Oil red O staining was used to characterize the change of hepatic pathology. The ultrastructure of mitochondria was examined by transmission electron microscopy. The hepatic malondialdehyde level and superoxide dismutase activity were measured by thiobarbituric acid method and xanthine oxidase method, respectively. Western blot assay was performed to detect the expression level of autophagic molecular signals including P62, Beclin, LC3B and nuclear factor-κB. The experimental protocol was approved by the Animal Ethic Committee of Renmin Hospital of Wuhan University (approval No. 2018-541).

RESULTS AND CONCLUSION: The serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and total cholesterol levels were significantly higher in the model group than the control group (P < 0.05). Compared with the model group, curcumin significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and total cholesterol (P < 0.05), but this effect was partly inhibited by 3-MA (P < 0.05). There was more cellular lipid deposition in the model group than the control group. Compared with the model group, curcumin significantly decreased cellular lipid deposition, but the decrease was partly inhibited by 3-MA. Compared with the control group, mitochondrial edema and cristae rupture (or even completely disappearing) were easily found in the model group. Curcumin significantly attenuated mitochondrial injury, which was partly inhibited by 3-MA. Hepatic superoxide dismutase activity in the model group was significantly lower than that in control group, and it significantly increased after curcumin treatment. The hepatic superoxide dismutase activity in the curcumin+3-MA group was higher than that in model group but lower than that in the curcumin group. Hepatic malondialdehyde level in the model group was higher than that in the control group, and it significantly decreased after curcumin treatment. Whereas the hepatic malondialdehyde level in the curcumin+3-MA group was lower than that in model group but higher than that in the curcumin group. Compared with the control group, the model group showed significantly increased expressions of P62, nuclear factor-κB but decreased expressions of Beclin-1 and LC3II/LC3I (all P < 0.05). Curcumin significantly decreased the expressions of P62 and nuclear factor -κB and increased the expressions of Beclin-1 and LC3II/LC3I; however, these changes were partly inhibited by 3-MA (all P < 0.05). Therefore, curcumin can effectively prevent hepatic steatosis in experimental non-alcoholic fatty liver disease rats by regulating inflammatory reaction and oxidative stress via activation of autophagy.

Key words: curcumin, non-alcoholic fatty liver disease, autophagy, inflammatory reaction, oxidative stress

CLC Number:

Wu Pengbo, Song Qi, Yu Yuanjie, Rao Qian, Zhang Guo, Guo Yitian, Tan Shiyun. Curcumin ameliorates inflammatory reaction and oxidative stress through activation of autophagy in experimental non-alcoholic fatty liver disease rats [J]. Chinese Journal of Tissue Engineering Research, 2020, 24(11): 1720-1725.

Figures/Tables 6

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