Anti-type 2 diabetes mellitus activity of Citrus reticulata -derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays | Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007 Skip to main content Skip to main navigation menu Skip to site footer Open Menu Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007 Home Food Science Publisher Functional Food Center Current Archives About About the Journal Aims and Scope Contact Editing Services Editorial Team Express Peer Review Graphical Abstract Journal Insights Privacy Statement Submissions Announcements Search Search Register Login Home / Archives / Vol. 15 No. 12 (2025): December 2025 / Research Articles Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays Authors Hanhua Wang Mingyue Li Yanyue Wang DOI: https://doi.org/10.31989/ffhd.v15i12.1802 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 (< –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 Downloads [Abstract] [Full Article] Published 2025-12-10 Issue Vol. 15 No. 12 (2025): December 2025 Section Research Articles License Copyright (c) 2025 Hanhua Wang, Mingyue Li, Yanyue Wang This work is licensed under a Creative Commons Attribution 4.0 International License. Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License. This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged. By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained. About the Journal      Editing Services      Graphical Abstract      Journal Insights        Submissions        Editorial Team       Privacy Statement        Contact        Current        Archives   Open Journal Systems Hosting and Support by: OpenJournalSystems.com