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Emerging evidence suggests that plant-derived polyphenols may offer neuroprotective benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This pilot study aimed to investigate the therapeutic potential of polyphenol-rich cocoa extract in a valproic acid (VPA)-induced zebrafish model of ASD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Zebrafish were exposed to 3\u202f\u03bcM VPA, cocoa powder providing 2.5 \u03bcM (\u2013)-epicatechin, a combination of both, or left untreated. Behavioral phenotyping was conducted using DanioVision and gut morphology was assessed. Untargeted metabolomic and proteomic profiling was performed followed by univariate and multivariate analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VPA exposure induced ASD-like behavioral hyperactivity, and severe gastrointestinal abnormalities. Cocoa co-treatment ameliorated both behavioral performance and gut architecture. Metabolomic profiling revealed VPA-associated disruptions in neurotransmission, methylation, mitochondrial function and redox homeostasis. Proteomic profiling showed elevated levels of trafficking protein particle complex subunit 11, proteasomal ubiquitin receptor, betaine-homocysteine S-methyltransferase 1 (BHMT-1), and desmoplakin-A, consistent with genotoxic stress and impaired protein trafficking. Cocoa co-treatment normalized BHMT-1 and desmoplakin-A expression and mitigated broader metabolic dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these results suggest that polyphenol-rich cocoa may represent a promising multi-targeted nutraceutical approach for mitigating ASD-related neurodevelopmental and metabolic disturbances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-026-02482-w","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:18:05Z","timestamp":1781803085000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Untargeted metabolomics and proteomics reveals cocoa-mediated mitigation of valproic acid-induced dysregulation in a zebrafish model of autism: pilot study"],"prefix":"10.1007","volume":"22","author":[{"given":"Jeffrey","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isra\u2019a","family":"Haj-Husein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Ghafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Khorraminezhad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Iskandar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Zaouter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lekha","family":"Sleno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunmoogum A.","family":"Patten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stan","family":"Kubow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"2482_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/2040-2392-5-43","volume":"5","author":"D Adamsen","year":"2014","unstructured":"Adamsen, D., Ramaekers, V., T Ho, H., Britschgi, C., R\u00fcfenacht, V., Meili, D., Bobrowski, E., Philippe, P., Nava, C., Van Maldergem, L., & Bruggmann, R. 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