Gunawan Shirly, Soetikno Vivian, Purwaningsih Erni Hernawati, Ferdinal Frans, Wuyung Puspita Eka, Ramadhani Dwi
Department of Pharmacology, Faculty of Medicine, Universitas Tarumanagara, Jakarta, Indonesia.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
J Exp Pharmacol. 2024 Dec 17;16:455-466. doi: 10.2147/JEP.S492971. eCollection 2024.
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.
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.
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.
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.
内质网（ER）应激在高脂饮食诱导的非酒精性脂肪性肝病（NAFLD）发病机制中起重要作用。本研究旨在探讨6-G对代谢综合征（MetS）大鼠内质网应激诱导的NAFLD减轻作用的影响。
25只雄性Sprague-Dawley大鼠给予高脂高果糖（HFHF）饮食16周。大鼠每天口服一次6-G（50、100和200mg/kg体重），持续8周。在第16周，处死所有动物，采集血清和肝组织进行生化和结构分析。
NAFLD肝大鼠显示GRP78以及ER相关凋亡蛋白如IRE1、TRAF2、p-JNK和p-NF-κB的蛋白表达升高，而这三种剂量的6-G处理可使其显著降低。此外，在NAFLD大鼠肝脏中观察到肝脏凋亡和非酒精性脂肪性肝炎（NAS）评分显著增加，三种剂量的6-G处理也使其减轻。6-G处理还降低了血清ALT、AST和ALP水平。
综合所有研究结果，提示6-G处理可能是治疗大鼠内质网应激诱导的NAFLD的潜在候选疗法。
