Phytochemical, Antioxidant, and Anticancer Evaluation of Passiflora edulis Leaf Extract Using In Vitro and In Silico Approaches

Abstract

Hepatocellular carcinoma (HCC) is a major global health burden, and there is an urgent need to develop novel therapeutic agents with more efficacious safety profiles. In the current studies, methanolic leaf extract of Passiflora edulis was characterized for its phytochemical composition and biological activities in an integrated in vitro and in silico approach. Qualitative phytochemical screening indicated that bioactive secondary metabolites such as flavonoids, saponins and steroids were present. The extract showed concentration-dependent antioxidant activity, with 81% DPPH radical scavenging at a maximum, suggesting potent free radical neutralization capability. The MTT assay was used to assess cytotoxicity in HepG2 human liver cancer cells, finding a moderate antiproliferative effect with an IC₅₀ value of 251 µg/mL. GC–MS analysis revealed different phytoconstituents and 13-docosenamide (Z) was predominant, however included some compounds as hexadecane and N-isopropyl-3-phenylpropanamide. The molecular docking studies showed moderate binding affinities (−6.5 to −7.8 kcal/mol) of selected compounds against the target protein (PDB ID: 3GCW), which represented PCSK9–LDLR complex. Significantly, N-isopropyl-3-phenylpropanamide demonstrated the most favourable binding interactions by engaging in both hydrogen bonding and hydrophobic interactions with key amino acid residues, indicating potential modulation of protein function. Since the PCSK9–LDLR axis plays a crucial role in lipid metabolism and has also become increasingly implicated in HCC progression, these results suggest that the biological activity of P. edulis extract may be mediated through multi-target interactions with cancer-associated metabolic pathways. Nonetheless, moderate cytotoxic potency and basic extract evaluation justify further studies. Bioactivity-guided fractionation will be necessary to identify active P. edulis–derived compounds, the mechanism of action needs further validation, and in vivo evaluation should be performed toward demonstrating their therapeutic potential.