IN SILICO AND IN VITRO ASSESSMENT OF ANGIOTENSINCONVERTING ENZYME INHIBITORY ACTIVITY OF DIGERA MURICATA EXTRACTS

AbstractBackground: Hypertension is a leading global health concern, often managed with syntheticACE inhibitors such as captopril, enalapril, and lisinopril. While effective, these drugs areassociated with adverse effects during long-term use, prompting interest in safer, plant-basedalternatives. Digera muricata, a medicinal plant rich in phytochemicals, has shown diversepharmacological activities, but its ACE inhibitory potential remains underexplored.Methods: Stem extracts of Digera muricata were prepared using ethanol (EEDM) andaqueous ethanol (AEDM, 70:30 v/v) by maceration. Extraction yield, total phenolic content,and total flavonoid content were determined. ACE inhibitory activity was assessed using theCushman and Cheung HHL-based method, with IC₅₀ values calculated. Molecular dockingstudies were performed against human ACE (PDB ID: 4AHP) using SWISS dock, and ligandinteractions were analyzed with Molegro Molecular Viewer.Results: AEDM produced a higher yield (13.18%) than EEDM (7.64%) and containedgreater phenolic (95.88 ± 0.84 mg GAE/g) and flavonoid (61.42 ± 0.78 mg QE/g) levels.Both extracts exhibited concentration-dependent ACE inhibition, with AEDM showingsuperior activity (83.56 ± 1.04% inhibition at 1000 µg/mL; IC₅₀ = 405.68 µg/mL) comparedto EEDM (71.38 ± 1.12%; IC₅₀ = 577.24 µg/mL). Docking studies identified gallic acid as themost promising compound (binding affinity -7.624 kcal/mol), forming stable interactionswith key ACE residues.Conclusion: Digera muricata stem extracts, particularly AEDM, demonstrate significantACE inhibitory activity, likely due to their high phenolic and flavonoid content. Gallic acidemerged as a potential lead compound, correlating well with experimental findings. Theseresults highlight Digera muricata as a promising source of natural ACE inhibitors andprovide a foundation for future pharmacological and clinical investigations in hypertensionmanagement.