<i>In Silico</i> Evaluation of Anti-diabetic and Immunomodulatory Activities of Phytoconstituents from <i>Lepidagathen pungens</i> and <i>Capparis grandis</i>

Background: Diabetes mellitus is strongly associated with oxidative stress and immunological dysfunction, exacerbating metabolic and inflammatory challenges. Therapeutic compounds produced from bioactive plant molecules have garnered significant interest due to their extensive impact on various biological targets. Aim: This study employed molecular docking and in vitro antioxidant assays to assess the antioxidant, immunomodulatory, and anti-diabetic activities of bioactive compounds derived from Capparis grandis and Lepidagathen pungens. Methods: To elucidate the interactions between Cristatin-A from L. pungens and Cappariloside from C. grandis with two target proteins, Human Collagenase-3 (MMP-13) and the c-Src SH3 domain mutant T125S, we performed a molecular docking study with Molegro Virtual Docker (MVD). These proteins are involved in pathways that govern metabolism and the immune system. We examined its docking efficacy with two reference medications, Glibenclamide and Azathioprine. We employed tests to evaluate the scavenging of hydroxyl radicals, superoxide radicals, and lipid peroxidation to ascertain the efficacy of the hydro-alcoholic extract of C. grandis (HAECG) against free radicals. Results: Cristatin-A and Cappariloside demonstrated robust hydrogen bond interactions with both target proteins and achieved favourable MolDock scores in docking assessments. This signifies that their binding affinity surpasses that of the reference medications. These interactions indicate the potential for a dual role in modulating the immune system and glycemic control. The IC₅₀ values of 22.21 µg/mL for hydroxyl radicals and 22.04 µg/mL for superoxide radicals demonstrate that HAECG displayed considerable radical scavenging activity in antioxidant assessments. Consistent with standard treatment, the extract suppressed lipid peroxidation, exhibiting an IC₅₀ value of 27.618 µg/mL. Conclusion: The data indicate that C. grandis and L. pungens are abundant in bioactive chemicals with potential antioxidant, immunomodulatory, and anti-diabetic effects. These plants may yield potential novel plant-based therapeutics for metabolic and immune system disorders. Major Findings: In comparison to conventional pharmaceuticals, Cristatin-A and Cappariloside received superior docking scores owing to their robust binding affinity for MMP-13 and c-Src SH3 domain proteins. The hydro-alcoholic extract of C. grandis shows considerable antioxidant activity, perhaps aiding in the management of oxidative stress linked to diabetes and immune system problems.