{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:10:09Z","timestamp":1778929809043,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2010alcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are prevalent metabolic disorders that frequently coexist, yet their shared molecular mechanisms remain poorly understood, and current therapies often yield suboptimal outcomes.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Lycium barbarum<\/jats:italic>\n                    <\/jats:styled-content>\n                    L. (\n                    <jats:italic>Lycii fructus<\/jats:italic>\n                    , LF), a traditional medicinal herb, has demonstrated clinical efficacy in treating both conditions, but its mechanism of action in comorbidity management remains unclear. Active LF compounds were identified via the TCMSP database, with potential targets predicted using Swiss Target Prediction and PharmMapper. Disease\u2010associated proteins for NAFLD and DM were curated from OMIM, GeneCards, DisGeNET, UniProt, DrugBank, and TTD. A protein\u2013protein interaction (PPI) network was constructed from these targets, and GO and KEGG pathway analyses were performed using the DAVID platform. Key targets were further refined through network module analysis via Metascape. Drug\u2010likeness of bioactive compounds was assessed using SwissADME and ADMETlab 2.0. Molecular docking and dynamics simulations validated interactions between core targets and LF compounds. Mendelian randomization (MR) analysis tested causal relationships between core genes and disease phenotypes. We identified 58 shared therapeutic targets for NAFLD\u2010DM comorbidity, including HSP90AA1, ESR1, MMP9, EGFR, AKT1, and CASP3. GO analysis implicated LF in blood pressure regulation and glucose\u2010stimulated insulin secretion. KEGG pathways highlighted modulation of MAPK, PI3K\u2010Akt, FoxO, and mTOR signaling. 24\u2010methylenelanost\u20108\u2010enol and cryptoxanthin monoepoxide emerged as core bioactive compounds with favorable drug\u2010likeness. Molecular docking confirmed strong binding of 24\u2010methylenelanost\u20108\u2010enol to HSP90AA1 and cryptoxanthin monoepoxide to MMP9, further supported by dynamics simulations. MR analysis revealed a significant causal role for CASP3 in both NAFLD and DM, aligning with network pharmacology predictions. LF's therapeutic effects on NAFLD\u2010DM comorbidity likely arise from terpenoid and cryptoxanthin mediated modulation of apoptosis and inflammation pathway. This study identifies shared molecular networks, proposes candidate mechanisms for LF's efficacy, and provides a framework for targeting multifactorial metabolic diseases.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70256","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:09:34Z","timestamp":1748304574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating the Mechanisms of\n                    <i>Lycii fructus<\/i>\n                    in Treating Nonalcoholic Fatty Liver Disease and Diabetes Comorbidity Through Network Pharmacology and Molecular Dynamics"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-4140","authenticated-orcid":false,"given":"Peng","family":"Sun","sequence":"first","affiliation":[{"name":"Science and Technology Center Ningxia Medical University  Yinchuan China"},{"name":"Ningxia Hui Autonomous 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