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Compound 5, a tricarboxylic acid derivative, is reported for the first time as abundantly accumulated in this fungus. Aging-relevant assays showed that 1 potently inhibited \u03b1-glucosidase (IC50 = 0.02 mM, surpassing acarbose) and moderately inhibited acetylcholinesterase (IC50 = 0.29 mM); 5 competitively inhibited alkaline phosphatase (IC50 = 5.47 mM) and suppressed GluN2A-containing NMDA receptor currents (IC50 = 0.40 mM), the first such dual report for a fungal tricarboxylic acid; and 4 inhibited tyrosinase (IC50 = 0.80 mM) comparably to kojic acid. HPLC confirmed meaningful recovery under mild hydro-alcoholic extraction compatible with functional food processing. These multifunctional small molecules target carbohydrate metabolism, cognition, and skin homeostasis, supporting T. fuciformis as a source of healthy-aging food ingredients.<\/jats:p>","DOI":"10.3390\/foods15173045","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:03Z","timestamp":1788150243000},"page":"3045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Six Bioactive Small Molecules from Tremella fuciformis with Potential for Healthy Aging"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6708-9145","authenticated-orcid":false,"given":"Feifei","family":"Wang","sequence":"first","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yuxuan","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Ziying","family":"Cai","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Shidong","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Lingjun","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1557-7542","authenticated-orcid":false,"given":"Yongbiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11592","DOI":"10.1039\/D2FO01951E","article-title":"Anti-aging potency correlates with metabolites from in vitro fermentation of edible fungal polysaccharides using human fecal intestinal microflora","volume":"13","author":"Zhang","year":"2022","journal-title":"Food Funct."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1039\/D2FO01683D","article-title":"Therapeutic potential and nutritional significance of Ganoderma lucidum\u2014A comprehensive review from 2010 to 2022","volume":"14","author":"Swallah","year":"2023","journal-title":"Food Funct."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/jmf.2016.3740","article-title":"Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases","volume":"20","author":"Phan","year":"2017","journal-title":"J. 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