Bioprospection of Hura crepitans metabolites against oxidative stress and inflammation: An in vitro and in silico exploration

Background: Despite the recognized therapeutic potential of Hura crepitans, its mechanistic antioxidant and anti-inflammatory actions remain underexplored. Methods: This study investigates the inhibitory effects, binding stability, and interactions of metabolites from H. crepitans on oxidative and inflammatory biomarkers/targets using in vitro analyses and molecular dynamics (MD) simulations. Results: In vitro experiments revealed significant dose-dependent antioxidant and anti-inflammatory activities. The crude methanolic extract (CMEHC) showed notable half-maximal inhibitory concentration (IC50) values for antioxidant assays, such as diphenyl picrylhydrazine (45.51 µg/mL) and ferric-reducing power (10.86 µg/mL), with comparable performance to standard ascorbic acid. Anti-inflammatory activities, including protein denaturation, proteinase inhibition, and membrane stabilization, demonstrated IC50 values between 77.29– 171.30 µg/mL. Liquid chromatography-mass spectrophotometry identified five primary compounds, predominantly phenolics, with rutin as the most abundant. Computational analyses confirmed these compounds' safety profiles, robust binding interactions, and stability against oxidative and inflammatory targets, with rutin forming the most stable interactions. Conclusion: These findings highlight the potential of H. crepitans phenolics as alternative therapies for oxidative stress and inflammation, warranting further drug development studies.