Anti-inflammatory Potentials of Hydromethanolic Extract of Hibiscus sabdariffa Seeds: Insights from Phytochemical, In vitro, and In silico Analyses

Abstract Inflammation, a complex physiological response implicated in various diseases including cardiovascular disorders, diabetes, neurodegenerative diseases, and cancer; and is regulated by enzymes such as cyclooxygenase-2 (COX-II) and 5-lipoxygenase (5-LOX). This study investigated the anti-inflammatory potential of bioactive compounds from the hydromethanolic extract of Hibiscus sabdariffa seeds (HEHSS) using in vitro and in silico approaches. The HEHSS was subjected to phytochemical analysis using gas chromatography–flame ionization detection (GC-FID), which revealed the presence of nineteen bioactive compounds, with tannin, catechin, dihydrocystine, and oxalate being predominant. In vitro anti-inflammatory assays demonstrated concentration -dependent inhibitory effects against albumin denaturation (22.06–51.75%), heat-induced hemolysis (16.81–43.17%), and lipoxygenase activity (14.01–42.99%), suggesting significant protein-stabilizing, membrane-protective, and enzyme-inhibitory activities. ADME profiling acknowledged catechin, kaempferol, naringenin, and ribalinidine as promising candidates with favourable pharmacokinetic properties with no violations of the Lipinski rules. Molecular docking of selected ligands against inflammation-related COX-II and 5-LOX revealed strong binding affinities of catechin (−7.33 kcal/mol), naringenin (−7.14 kcal/mol), and kaempferol (−6.84 kcal/mol) to COX-II, as well as naringenin (−6.17 kcal/mol), ribalinidine (−5.72 kcal/mol), and catechin (−5.24 kcal/mol) to 5-LOX, outperforming standard reference inhibitors (aspirin, indomethacin, zileuton and licofelone). These results highlight the dual inhibitory capability of H. sabdariffa seed phytochemicals on COX-II and 5-LOX, emphasizing their relevance in suppressing the synthesis of prostaglandin and leukotriene. The findings establish H. sabdariffa seeds as a valuable source of multifunctional phytochemicals, which could be harnessed for the development of cheaper, safer, plant-based and sustainable anti-inflammatory therapeutics.