Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays

Abstract

Background: Citrus reticulata-derived materials (CRDMM) are representative medicinal and edible resources, yet their systematic evaluation for anti-type 2 diabetes mellitus (T2DM) potential remains to be fully elucidated. Objective: This study aimed to investigate the anti-T2DM potential of CRDMM and explore the underlying mechanisms of action using an integrated experimental and computational approach. Results: In vitro assays demonstrated significant α-glucosidase inhibitory activity across 16 CRDMM extracts, with Guangchenpi exhibiting the strongest potency (IC₅₀: 2.5–3.8 mg/mL). Network pharmacology analysis identified 10 active compounds and 74 potential targets, among which AKT1, TP53, PPARG, and PTGS2 were highlighted as core targets via protein-protein interaction analysis. Pathway enrichment suggested involvement in lipid metabolism and inflammatory pathways. Molecular docking confirmed strong binding affinities (