{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:41:18Z","timestamp":1792712478636,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174088"],"award-info":[{"award-number":["82174088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104600"],"award-info":[{"award-number":["82104600"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Diabetes\u2010related depression (DD) is a challenging comorbidity characterized by self\u2010reinforcing interactions between metabolic dysfunction and affective disturbance, while conventional antidepressants and glucose\u2010lowering drugs often yield suboptimal outcomes with adverse effects. This study investigated the therapeutic potential of fingered citron extract (FCE), traditionally used for metabolic and inflammatory conditions, in alleviating DD and elucidated its underlying mechanisms. Using a DD mouse model induced by high\u2010fat diet, streptozotocin, and chronic unpredictable mild stress, we administered FCE at varying doses and employed a multimodal approach including behavioral tests, biochemical assays, UPLC\u2010MS\/MS, network pharmacology, molecular docking, molecular dynamics simulation, immunofluorescence, Western blotting, and cellular validation. The results showed that FCE significantly reversed weight loss, reduced fasting blood glucose, and ameliorated depressive\u2010like behaviors. It also restored 5\u2010HT, DA, NE, and BDNF, lowered glutamate and pro\u2010inflammatory cytokines (IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1), and increased anti\u2010inflammatory IL\u201010. UPLC\u2010MS\/MS analysis identified 34 serum\u2010absorbed bioactive constituents, and integrated analyses highlighted neohesperidin (NH) and SRC as a candidate active constituent\u2010target axis. FCE suppressed pancreatic SRC overactivation, improved pancreatic and brain insulin (INS) related signaling, and these molecular changes were associated with behavioral recovery. In\u00a0vivo pharmacodynamic validation further showed that NH partially reproduced the metabolic, behavioral, and biochemical effects of FCE in DD mice. In high\u2010glucose\u2010induced MIN6 cells, NH enhanced insulin secretion, mitigated reactive oxygen species accumulation, and restored mitochondrial membrane potential, whereas these protective effects were markedly attenuated after SRC knockdown. Collectively, these findings suggest that FCE ameliorates DD, at least in part, through NH\/SRC\u2010mediated regulation of insulin signaling and neuroinflammation, supporting its potential as a multi\u2010target natural therapeutic candidate for DD.<\/jats:p>","DOI":"10.1002\/ptr.70492","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:36:08Z","timestamp":1792712168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fingered Citron Extract Ameliorates Diabetes\u2010Related Depression via Targeting\n                    <scp>SRC<\/scp>\n                    \u2010Mediated Insulin Signaling and Neuroinflammation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3377-542X","authenticated-orcid":false,"given":"Shun","family":"Guo","sequence":"first","affiliation":[{"name":"College of Life Sciences, Northwest University  Xi'an Shaanxi People's Republic of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northwest University  Xi'an Shaanxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-6057","authenticated-orcid":false,"given":"Yajun","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northwest University  Xi'an Shaanxi People's Republic of 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