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

Shirly Gunawan,1 Vivian Soetikno,2 Erni Hernawati Purwaningsih,3 Frans Ferdinal,4 Puspita Eka Wuyung,5,6 Dwi Ramadhani7 1Department of Pharmacology, Faculty of Medicine, Universitas Tarumanagara, Jakarta, Indonesia; 2Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Tarumanagara, Jakarta, Indonesia; 5Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 6Animal Research Facility, IMERI, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 7Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy, National Research and Innovation Agency, Banten, IndonesiaCorrespondence: Vivian Soetikno, Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Salemba Raya no. 6, Jakarta, 10430, Indonesia, Tel +62 21 31930481, Email [email protected]: 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, endoplasmic reticulum, diabetes, insulin resistance, inflammation