Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays
DOI:
https://doi.org/10.31989/ffhd.v15i12.1802Abstract
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 (< –7.0 kcal/mol) between key flavonoids (e.g., neohesperidin_qt and nobiletin) and the core targets. ADMET predictions indicated favorable drug-likeness, despite potential nephrotoxicity risks.
Novelty: This study is the first to integrate multi-approach validation—combining in vitro bioactivity, network pharmacology, molecular docking, and ADMET profiling—to systematically reveal that CRDMM exerts anti-T2DM effects via a multi-component, multi-target mechanism.
Conclusion: The results provide a scientific basis for developing CRDMM as functional food ingredients or dietary supplements for blood glucose management in T2DM.
Keywords: Citrus reticulata, type 2 diabetes mellitus, α-glucosidase inhibition, network pharmacology, molecular docking, functional food, medicinal-food homology, nobiletin
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