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.
PMID:39712345 | PMC:PMC11662909 | DOI:10.2147/JEP.S492971