<![CDATA[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.]]>
