EXPLORING THE MOLECULAR MECHANISMS OF EPICATECHIN FROM THE ENDOPHYTIC FUNGUS CHAETOMIUM GLOBOSUM IN RHEUMATOID ARTHRITIS USING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING

Abstract

Endophytic fungi from medicinal plants represent valuable sources of bioactive secondary metabolites with diverse pharmacological properties. This study aimed to characterize the metabolite profile of Chaetomium globosum SK04 isolated from Drynaria quercifolia and explore its molecular mechanism in rheumatoid arthritis. The ethyl acetate extract was chromatographically fractionated, and MF5 exhibited the highest anti-inflammatory activity among the fractions, with 79.86 ± 0.03% inhibition of albumin denaturation and 77.52 ± 0.04% HRBC membrane stabilization. LC–MS/MS profiling of MF5 identified eight metabolites, among which epicatechin showed a prominent peak and was selected for further analysis. A total of 126 non-redundant potential targets of epicatechin were identified, of which 43 overlapped with rheumatoid arthritis-associated targets. PPI network analysis highlighted AKT1 as a central hub among the core targets. GO and KEGG pathway enrichment analyses revealed significant enrichment of biological processes and signalling pathways, particularly the PI3K–Akt signalling pathway. The 10 core pathways and 43 common targets were further integrated into a compound–target–pathway–disease network, in which AKT1 occupied a central position. Molecular docking showed the highest binding of epicatechin to KDR at −9.57 kcal/mol. Thus, this study provides insights into the potential molecular mechanisms of epicatechin in rheumatoid arthritis.