6-Gingerol Reduces Tumor Necrosis Factor-Alpha Levels in the Brain of Metabolic Syndrome Rats

Abstract

Metabolic syndrome (MetS), with its associated abnormalities, is linked with oxidative stress and inflammation in the brain, leading to cognitive decline. As a natural compound with promising antioxidant properties derived from ginger, 6-gingerol (6G) could be a potential therapeutic candidate. This study aimed to investigate the effects of 6G on alleviating inflammation, oxidative stress, and insulin signaling in the brain tissue of MetS rats. Male Sprague-Dawley Rats were randomized into five groups: normal control, negative control, and three groups receiving increasing doses of 6G for 8 weeks. A high-fat diet and a low-dose streptozotocin injection induced MetS. Brain tissues were analyzed for tumor necrosis factor (TNF-ɑ), interleukin-1 (IL-1β), malondialdehyde (MDA), glutathione peroxidase (GPx), glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) levels. The study was conducted at the Pharmacokinetics Laboratory Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, in January-February, 2023. TNF- levels were significantly higher in the MetS group compared to the normal-control group (95% CI: -4.4 – -74.9; p = 0.024), whereas there were no significant differences in IL-1, MDA, GPx, GLP-1, and GLP-1R levels between the MetS and normal-control groups. Administration of 6G at 50 mg/kg/day significantly reduced TNF levels compared with the MetS group (95% CI: -12 to -82; p = 0.006), whereas 6G at 100 and 200 mg/kg/day did not improve all parameters. The present findings suggest that 6G, particularly at a dose of 50 mg/kg, may exert anti-inflammatory effects in MetS-induced brain inflammation. However, the importance of dose optimization for the potential translational application of 6G remains to be further researched.