Parasitic diseases are some of the most lethal and pervasive infections globally, causing millions of cases of morbidity and mortality annually. Plasmodium falciparum is the predominant vector-borne pathogen, resulting in 0.5 million fatalities annually. Malaria, caused by Plasmodium falciparum, continues to be a significant worldwide health issue, requiring the development of novel treatment medicines to address increasing medication resistance. This study undertakes a focused in silico screening of phytochemicals derived from Centella asiatica against dihydrofolate reductase-thymidylate synthase (PfDHFR-TS), represented by PDB ID: 3BWK. This work investigated molecular modelling to clarify the probable mechanism of its anti-malarial activity through the suppression of falciparum proteins. Campesterol exhibits a maximal binding affinity (docking score: −8.6 Kcal/mol) for FP-2 from Plasmodium falciparum, as determined by our molecular docking investigation of 15 bioactive compounds from Centella asiatica. However, Ursolic acid and rutin also showed potential activity with significant docking scores (−8.5 and 8.4 Kcal/mol). Campesterol, recognized as a possible inhibitor of falciparum, offers a viable pathway for the treatment of malaria, necessitating additional investigation into its therapeutic use. This research provides significant insights into the molecular interactions between phytochemicals, facilitating innovative and successful strategies for malaria treatment. Our research indicates that polyphenols derived from Centella asiatica exhibit significant pharmacological potential against several biological targets.

Angiogenesis is a fundamental process in wound healing that facilitates tissue repair and regeneration by forming new blood vessels. Natural polyphenols have attracted considerable attention as potential therapeutic agents owing to their antioxidant, anti-inflammatory, and tissue-protective properties. In the present study, an in silico approach was employed to investigate the angiogenic potential of 28 natural polyphenols targeting the vascular endothelial growth factor receptor-2 (VEGFR-2; PDB ID: 3VHE), a key regulator of angiogenesis and vascular remodelling. Molecular docking was performed using AutoDock, and Dexpanthenol, a clinically used wound-healing agent, was selected as the reference standard. The investigated compounds exhibited binding affinities ranging from −5.3 to −10.6 kcal/mol. Among them, kaempferol and fisetin demonstrated the highest binding affinity (−10.6 kcal/mol), followed by quercetin (−10.3 kcal/mol), while apigenin, luteolin, chrysin, naringenin, and hesperetin each exhibited docking scores of −10.2 kcal/mol. Notably, several polyphenols displayed stronger binding affinities than Dexpanthenol (−5.1 kcal/mol). Molecular interaction analysis revealed stable ligand–receptor complex formation through hydrogen bonding, π–π stacking, and hydrophobic interactions involving key amino acid residues, including CYS919, ASP1046, VAL848, LEU1035, PHE1047, and CYS1045. Furthermore, ADMET prediction studies demonstrated favourable pharmacokinetic properties, acceptable toxicity profiles, and compliance with drug-likeness criteria for the top-performing compounds. These findings suggest that kaempferol and fisetin are promising natural VEGFR-2 modulators with potential applications in angiogenesis-mediated wound healing. Further molecular dynamics simulations and experimental validation are warranted to confirm their therapeutic potential and underlying mechanisms of action.