BACKGROUND: Obesity is linked to chronic low-grade inflammation and increased oxidative stress that may disrupt hypothalamic metabolic homeostasis. Excess nutrient intake activates inflammatory signaling and promotes glial reactivity, contributing to neuroinflammatory remodeling. Superoxide dismutase (SOD) is a key enzymatic antioxidant marker reflecting hypothalamic defense capacity. However, whether natural antioxidants can simultaneously restore SOD activity and attenuate obesity-induced glial reactivity remains unclear. Among many natural antioxidant, Moringa oleifera is rich in bioactive compounds with antioxidant properties that may attenuate neuroinflammation. Therefore, this study was conducted to evaluated the effect of M. oleifera fruit extract (MOFE) on hypothalamic total SOD activity and histopathological features of glial reactivity in obese Wistar rats.METHODS: Male Wistar rats were divided into four groups: normal control, obese control, and two treatment groups. For obese control and treatment groups, obesity was induced for 8 weeks using a high-fat/high-sucrose diet. Fresh M. oleifera fruit pods were macerated to produce MOFE. Following the obesity-induction, the two treatment groups were treated with 500 and 1,000 mg/kgBW/day MOFE for 4 weeks. A hydroxylamine-based assay was employed to measure total SOD activity of hypothalamic tissue homogenate. Meanwhile, hematoxylin-eosin (HE) was used to stain hypothalamic sections for glial reactivity scoring.RESULTS: After the obesity induction, the obesity-induced rats showed elevated Lee Index, but after the treatment with 500 and 1,000 mg/kgBW/day MOFE, the Lee Index decreased for 26.61±3.53% and 26.32±0.93%, respectively, which is greater compared to obese control. MOFE administration was also able to improve hypothalamic SOD activity (64.75±1.29 U/mL and 65.78±0.74 U/mL). MOFE groups also exhibited predominantly milder histopathological changes and glial reactivity than obese controls.CONCLUSION: MOFE administration lowers Lee Index, improves hypothalamic SOD activity, reduces glial reactivity and improves neuroinflammation changes in obese rats, suggesting that MOFE might be potential agent for obesity-related oxidative-inflammatory brain injury. KEYWORDS: Moringa oleifera, obesity, oxidative stress, superoxide dismutase, hypothalamus, gliosis, Wistar rat