6-Gingerol, a Bioactive Compound of Zingiber officinale, Ameliorates High-Fat High-Fructose Diet-Induced Non-Alcoholic Related Fatty Liver Disease in Rats

J Exp Pharmacol. 2024 Dec 17:16:455-466. doi: 10.2147/JEP.S492971. eCollection 2024.

Abstract

Purpose: Endoplasmic reticulum (ER) stress has a prominent role in the pathogenesis of high-fat diet-induced non-alcohol related fatty liver disease (NAFLD). The aim of this study is to investigate the effects of 6-G on the reduction of ER stress-induced NAFLD in metabolic syndrome (MetS) rats.

Methods: Twenty-five male Sprague-Dawley rats were fed with a high-fat high-fructose (HFHF) diet for 16 weeks. The rats were treated orally with 6-G (50,100, and 200 mg/kgBW) once daily for eight weeks. At Week 16, all animals were sacrificed, and serum and liver tissue were harvested for biochemical and structural analysis.

Results: NAFLD liver rats were shown to have elevated protein expression of GRP78, and ER-associated apoptotic protein, such as IRE1, TRAF2, p-JNK, and p-NF-κB, which were considerably reduced by the 6-G at three doses treatment. Furthermore, a significant increase in liver apoptosis and non-alcoholic steatohepatitis (NAS) score were observed in the NAFLD rat liver and which were also attenuated by the 6-G treatment at three doses. 6-G treatment also reduced ALT, AST, and ALP serum levels.

Conclusion: Considering all the findings, it is suggested that the 6-G treatment could be a potential candidate therapy in treating ER stress-induced NAFLD in rats.

Keywords: 6-gingerol; diabetes; endoplasmic reticulum; inflammation; insulin resistance.

Grants and funding

This study was supported by a research grant from Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia with a grant number NKB-868/UN2.RST/HKP.05.00.2024. We thank our laboratory staff for supporting the study.