Exploring the potential value of aloe active components in inhibiting non-small cell lung cancer through network pharmacology

Abstract

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, and its management is challenged by profound molecular heterogeneity and inevitable resistance to targeted therapies. Natural products offer a valuable reservoir for anticancer drug discovery, yet the therapeutic potential of Aloe vera--a medicinal plant rich in structurally diverse bioactive compounds--remains insufficiently characterised in the context of NSCLC. Here, we employed an integrated strategy combining network pharmacology, protein-protein interaction analysis, Gene Ontology and KEGG enrichment, molecular docking, and 100-ns molecular dynamics simulations to comprehensively elucidate the multi-target and multi-pathway regulatory mechanisms of Aloe vera active constituents against NSCLC. We identified 369 aloe-derived targets and 5519 NSCLC-related genes, with 268 overlapping targets enriched in pathways involving EGFR signalling, PI3K/AKT/mTOR activation, p53 regulation, inflammation, apoptosis, and drug-resistance networks. Core hub genes included TP53, EGFR, AKT1, and STAT3. Molecular docking demonstrated strong spontaneous binding between key aloe compounds (such as aloe-emodin, aloeresin C, quercetin and sitosterols) and wild-type EGFR, mutant EGFR T790M/C797S, AKT1, and p53. Molecular dynamics simulations confirmed stable ligand-protein interactions, favourable hydrogen-bonding networks, and energetically favourable binding free energies. Collectively, our findings reveal a systematic, multi-level regulatory landscape through which Aloe vera may exert anti-NSCLC effects and highlight several candidate molecules with potential to enhance therapeutic efficacy or overcome EGFR-TKI resistance. This study provides a solid theoretical framework for subsequent experimental validation and the development of novel aloe-derived anticancer agents with low toxicity.