{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:07:14Z","timestamp":1789052834195,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["214522"],"award-info":[{"award-number":["214522"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"publisher"}]},{"award":["214522"],"award-info":[{"award-number":["214522"]}],"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"publisher","award":["FRB690042\/0162"],"award-info":[{"award-number":["FRB690042\/0162"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FRB690042\/0162"],"award-info":[{"award-number":["FRB690042\/0162"]}],"id":[{"id":"https:\/\/ror.org\/000025p04","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017170","name":"Chiang Mai University and the Thailand Research Fund (TRF) through the Research Team Promotion Grant (RTA) and the Senior Research Scholar","doi-asserted-by":"publisher","award":["N42A671052"],"award-info":[{"award-number":["N42A671052"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Androgenetic alopecia (AGA) involves dihydrotestosterone-driven follicular miniaturization compounded by oxidative stress and perifollicular inflammation, while current pharmacotherapies remain limited by adverse effects. Neem (Azadirachta indica A. Juss., Meliaceae) leaves, a phenolic- and limonoid-rich plant widely used in Southeast Asian traditional medicine, were fermented for seven days with a tri-culture consortium of Saccharomyces cerevisiae, Lactobacillus plantarum, and Aspergillus niger (TRI-NE) to evaluate whether expanded microbial diversity enhances bioactivity relative to the unfermented extract (UN-NE). TRI-NE significantly increased total phenolic content, rising from 315.30 to 564.70 mg GAE\/g by day 7, alongside an overall enhancement of antioxidant capacity across all assays. Moreover, untargeted metabolomics revealed compositional remodeling, with 67.47% of significantly altered metabolite features upregulated after fermentation, including selective enrichment of quercetin despite reductions in other polyphenols. In human hair follicle dermal papilla cells (HFDPCs) and complementary models, TRI-NE consistently outperformed UN-NE, enhancing paracrine-mediated fibroblast proliferation, preserving cell viability under potassium-channel blockade, suppressing lipopolysaccharide-induced inflammatory nitric oxide production, and attenuating oxidative membrane damage. At the transcriptional level, TRI-NE downregulated androgen metabolism (SRD5A1 and SRD5A2) and pro-regression genes (TGFB1) while upregulating Wnt\/\u03b2-catenin (CTNNB1), Sonic Hedgehog (SHH, SMO, and GLI1), and angiogenic (VEGF) pathway genes, with effects matching or exceeding standard hair-loss therapeutics. These findings indicate that TRI-NE confers superior bioactivity over the unfermented extract, supporting its potential as a multi-target cosmeceutical candidate for AGA.<\/jats:p>","DOI":"10.3390\/plants15182779","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:11:22Z","timestamp":1789049482000},"page":"2779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tri-Culture Fermentation of Neem (Azadirachta indica) Leaves Induces Phytochemical Remodeling and Enhances Multi-Target Bioactivities Relevant to Androgenetic Alopecia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8590-169X","authenticated-orcid":false,"given":"Anurak","family":"Muangsanguan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, 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