Chelesta-8,24-dien-3-ol in Ficus exasperata leaves enhances the prevention of sodium nitrite-induced hypoxia by binding to HIF-1 and NF-κB

In-silico and in-vivo methods were used to study Ficus exasperata leaves' n-hexane ethyl acetate fraction (NHEAF) phytochemicals that may protect against NaNO₂-induced hypoxic stress. The impact of NHEAF on enzymatic and non-enzymatic antioxidants, total ATPase, malondialdehyde, and the relative expression of human inducible factor-1 (HIF-1), nuclear respiratory factor-2, and nuclear factor kappa-B (NF-kB) were investigated, along with the docking of NHEAF phytochemicals to HIF-1 and NF-κB. Thirty female Wistar rats were divided into groups A, B, C, D, E and F (n = 5). Groups A and B were pretreated with olive oil (vehicle). While group C, D, E, and F were pretreated with standard drug (C = Vitamin E 100 mg/ kg bwt and Omega-3 essential fatty acid (72 mg Eicosapentaenoic acid (EPA) + 48 mg Docosahexaenoic acid (DHA)/ kg bwt), 30 mg/ kg bwt NHEAF (D) and 60 mg/ kg bwt NHEAF (E and F respectively) for 14 days followed by oral administration of NaNO₂ (80 mg/kg bwt) to groups B, C, D, and E. One of the eight NHEAF phytochemicals with the highest percentage total quantity is Cholesta-8,24-dien-3-ol, 4-methyl- (3β). Unlike group B, groups D and E pretreated with NHEAF were protected from the impairment of antioxidant defence and elevation of HIF-1 and NF-κB caused by NaNO₂ intoxication. Cholesta-8,24-dien-3-ol, 4-methyl- (3β), has the highest binding affinity for HIF-1 (ΔG = -8.6 kcal/mol) and NF-κB (ΔG = -7.6 kcal/mol) proteins among the NHEAF phytochemicals. Cholesta-8,24-dien-3-ol, 4-methyl-, (3β) may contribute to NHEAF's protection against s NaNO₂-induced hypoxic stress.