KNAPSACK-Based Network Pharmacology and Molecular Docking Reveal the Anti-Cervical Cancer Potential of Litsea garciae

Litsea garciae is a medicinal plant from the Lauraceae family known for its rich alkaloid and phenolic composition; however, its molecular mechanisms against cervical cancer remain insufficiently elucidated. This study aimed to investigate the anticervical cancer mechanisms of Litsea garciae bioactive compounds using a KNAPSACK-based network pharmacology approach integrated with molecular docking analysis. Phytocompounds associated with Litsea garciae were retrieved from the KNAPSACK database and subjected to target prediction. Cervical cancer–related genes (۴۹,۷۵۳ genes) were collected from GeneCards, OMIM, and GEO databases to identify overlapping targets. Protein–protein interaction (PPI) analysis was performed, and hub proteins were prioritized using the maximal clique centrality (MCC) algorithm. Functional enrichment analysis was conducted to elucidate key biological processes and signaling pathways. Molecular docking using AutoDock Vina was employed to evaluate binding affinity (ΔG) and inhibition constants (Ki) of selected compounds against prioritized hub proteins, with interaction analysis performed using BIOVIA Discovery Studio. Network pharmacology identified SRC, HSP۹۰AA۱, AKT۱, JUN, MAPK۱, MTOR, and GSK۳B as major hub proteins involved in cervical cancer–related signaling. Functional enrichment revealed significant association with PI۳K–Akt signaling, EGFR tyrosine kinase inhibitor resistance, and cancer-related pathways (FDR < ۱ × ۱۰⁻²⁰). Molecular docking showed favorable binding affinities ranging from −۶.۶۰ to −۸.۵۳ kcal/mol. Notably, (+)-boldine and actinodaphnine exhibited strong interactions with HSP۹۰AA۱, yielding nanomolar inhibition constants. Litsea garciae may exert anticervical cancer activity through multitarget modulation of kinase- and chaperone-centered signaling networks.

کلیدواژه ها:

Litsea garciae ، Cervical cancer ، Network pharmacology ، Molecular docking ، Multitarget therapy