ACTIVATION OF NRF2 HO-1 SIGNALING MEDIATES THE PROTECTIVE EFFECTS OF HIBISCUS SABDARIFFA AGAINST RESTRAINT STRESS-INDUCED OXIDATIVE DAMAGE IN FEMALE WISTAR RATS

Chronic psychological stress disrupts redox homeostasis, leading to oxidative damage, inflammation, and organ dysfunction. Females may be particularly vulnerable due to stress-related hormonal modulation of antioxidant signaling pathways. Hibiscus sabdariffa (HS) possesses documented antioxidant properties; however, its redox-regulated molecular mechanisms under stress conditions remain incompletely understood.This study investigated whether activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway underlies the protective effects of HS in restraint stress exposed female Wistar rats. Thirty-six rats were allocated to six groups: non-stressed control, stress control, stress + HS (250 or 500 mg/kg), and HS alone (250 or 500 mg/kg). Restraint stress was applied for 6 h/day for 14 days. Oxidative stress biomarkers, antioxidant enzyme activities, gene and protein expression of Nrf2, HO-1, TNF-a, and iNOS, and histopathological alterations in the brain, liver, and kidney were assessed. Restraint stress markedly increased lipid peroxidation and suppressed endogenous antioxidant defenses, accompanied by downregulation of Nrf2 and HO-1 and upregulation of TNF-a and iNOS. HS treatment dose-dependently restored antioxidant enzyme activities, reduced oxidative damage, activated Nrf2/HO-1 signaling, and attenuated inflammatory gene and protein expression. High-dose HS (500 mg/kg) normalized redox and inflammatory markers to near-control levels and conferred significant histological protection across examined tissues.