{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:17Z","timestamp":1791352217682,"version":"4.3.1"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Trigonelline (TG), a major alkaloid in fenugreek seed and coffee, has anti\u2010inflammatory and antioxidant activities. We investigated whether TG ameliorates Parkinson's disease (PD)\u2010related synucleinopathy and whether these effects are associated with inflammatory signaling and gut microbial\u2013metabolic alterations. Two\u2010sample Mendelian randomization (MR) was used to examine the relationship between genetically predicted circulating TG and \u03b1\u2010synuclein. In\u00a0vivo, AAV\u2010SynA53T C57BL\/6J mice received oral TG (5\u2009mg\/kg\/day) for 30\u2009days, followed by assessment of motor behavior, pSer129\u2010\u03b1\u2010syn pathology, dopaminergic markers, inflammatory readouts, intestinal barrier proteins, 16S rRNA profiles, and colon\u2010content metabolomics. MR supported a potential protective association between genetically predicted serum TG and reduced \u03b1\u2010synuclein. TG improved motor performance, reduced midbrain pSer129\u2010\u03b1\u2010syn signals, preserved dopaminergic markers, and attenuated inflammatory responses, accompanied by modulation of PI3K\/AKT and NF\u2010\u03baB signaling. TG also improved intestinal barrier\u2010associated features and altered the gut microbiota and metabolomic profile. A metabolomic feature tentatively annotated as Ganolucidic acid B was increased following TG treatment and correlated with several taxa enriched in the TG group; conditional network pharmacology suggested that its predicted targets were enriched in PD\u2010relevant inflammatory and PI3K\u2013AKT\u2010related pathways. Overall, TG may ameliorate synucleinopathy\u2010associated phenotypes in AAV\u2010SynA53T mice, accompanied by attenuated inflammation and gut microbiota\u2013metabolism remodeling. Further targeted metabolomic validation and causal intervention studies are warranted to clarify the contributions of specific metabolites and gut\u2010associated mechanisms.<\/jats:p>","DOI":"10.1002\/fsn3.72451","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:55:31Z","timestamp":1791348931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trigonelline Alleviates Neuroinflammation in AAV\u2010SynA53T Parkinson's Disease Model Mice: Involvement of PI3K\/AKT\u2013NF\u2010\u03baB Signaling and Gut Microbial\u2010Metabolic Remodeling"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4929-4438","authenticated-orcid":false,"given":"Mozi","family":"Chen","sequence":"first","affiliation":[{"name":"School of Public Health Wenzhou Medical University  Wenzhou Zhejiang 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