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Toxicol Appl Pharmacol. 2019 Jan 1;362:125-135. doi: 10.1016/j.taap.2018.11.001. Epub 2018 Nov 5.

6-gingerol ameliorates age-related hepatic steatosis: Association with regulating lipogenesis, fatty acid oxidation, oxidative stress and mitochondrial dysfunction.

Author information

1
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, China.
2
Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
3
Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
4
The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
5
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
6
Pharmafood Institute, Kyoto, Japan.
7
Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, Australia.
8
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing, China. Electronic address: wjwcq68@163.com.

Abstract

The prevalence of NAFLD increases with age. As the main active ingredient of ginger, 6-gingerol significantly improves lipid metabolism abnormalities in adult rodents. However, few studies have reported its effect on age-related NAFLD. This study was to investigate the effects of 6-gingerol on age-related hepatic steatosis and its potential targets. As expected, 6-gingerol dramatically normalized the hepatic triglyceride content, plasma insulin and HOMA-IR index of ageing rats. Mechanistically, 6-gingerol affected lipid metabolism by increasing β-oxidation and decreasing lipogenesis through activation of PPARα and CPT1α and inhibition of DGAT-2. Furthermore, 6-gingerol reversed the decreases in citrate, Cs and ATP, lessened the damage caused by ROS, and upregulated mitochondrial marker enzymes NOX, SDH, and SIRT3 in the ageing liver, indicating its ability to strengthen mitochondrial function. Our results showed 6-gingerol exerted a positive effect on insulin sensitivity by regulating Akt. In conclusion, the hepatic anti-steatotic effect of 6-gingerol is associated with inhibition of de novo lipogenesis, upregulation of fatty acid oxidation, reduction in oxidative stress and synergistic enhancement of mitochondrial function.

KEYWORDS:

6-Gingerol; Ageing; Fatty Liver; Mitochondria; PPARα

PMID:
30408433
DOI:
10.1016/j.taap.2018.11.001

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