Authors: Sangam K․C․ a, Shankar Thapa b, Nisha Adhikari a, Dirgha Raj Joshi a
a) School of Pharmacy, Karnali Academy of Health Sciences, Jumla, Nepal
b) Department of Pharmacy, Madan Bhandari Academy of Health Sciences, Hetauda, Nepal
सार
Background
Pathological angiogenesis is a key characteristic of cancer and other proliferative diseases and represents an important therapeutic target. Artemisia vulgaris L. (mugwort) is a medicinal plant with diverse phytochemicals; however, its anti-angiogenic mechanisms remain insufficiently explored.
Methods
Network pharmacology and molecular docking approaches were employed to investigate the anti-angiogenic potential of A. vulgaris. Phytochemicals were retrieved from the IMPPAT database and screened for drug-likeness and toxicity. Potential targets were predicted and intersected with anti-angiogenesis-related genes. Protein-protein interaction analysis, pathway enrichment, and molecular docking were performed to identify key targets and ligand-protein interactions, followed by molecular dynamics simulations to evaluate the stability of selected complexes.
Results
Twenty-eight compounds met ADME and toxicity criteria. Seventy-three overlapping targets associated with anti-angiogenesis were identified. Network analysis highlighted EGFR, AKT1, STAT3, HIF1A, CASP3, ESR1, PTGS2, BCL2L1, PPARG, and MMP9 as key hub genes. Pathway enrichment revealed significant involvement of the EGFR tyrosine kinase inhibitor resistance pathway. Molecular docking demonstrated stable interactions between selected phytochemicals and hub proteins, with the strongest binding observed for EGFR and AKT1 (up to -7.9 kcal/mol). Furthermore, molecular dynamic simulation demonstrated a stable β-caryophyllene–EGFR complex, while Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analysis revealed strong binding affinity (ΔG_bind = −75.20 ± 4.81 kcal/mol) predominantly driven by hydrophobic interactions.
Conclusion
Findings suggest that A. vulgaris phytochemicals may exert anti-angiogenic effects through multi-target modulation of EGFR-associated signaling pathways. This study provides a mechanistic basis for further experimental validation and supports the therapeutic potential of A. vulgaris in angiogenesis-related diseases.
