{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:13Z","timestamp":1787027053049,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetic neuropathy (DN) is one of the most common and debilitating complications of type 2 diabetes mellitus (T2DM), yet effective therapeutic strategies remain limited. Nervonic acid (NA) is recognized for its neuroprotective and anti-inflammatory properties. However, its role in DN has not been fully elucidated. In this study, we investigated the protective effects of NA against T2DM-induced DN using a zebrafish model and explored the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>T2DM was induced in zebrafish larvae through a high-fat, high-glucose diet combined with a low dose of streptozotocin. Larvae were subsequently treated with NA at concentrations of 125, 250, or 500\u00a0\u03bcg\/mL. Motor function, myelin integrity, neutrophil infiltration, and reactive oxygen species (ROS) levels were evaluated using fluorescence imaging and histological staining. Gene expression analysis was performed by quantitative real-time PCR. Metabolomics coupled with KEGG enrichment analysis was applied to identify NA-regulated metabolic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NA significantly preserved myelin integrity, reduced neutrophil infiltration, and lowered ROS levels in DN zebrafish. Expression of myelin-related genes (\n                      <jats:italic>mbpa<\/jats:italic>\n                      and\n                      <jats:italic>mpz<\/jats:italic>\n                      ) was upregulated, while pro-inflammatory cytokines were downregulated following NA treatment. Metabolomic profiling revealed that NA reversed diabetes-associated dysregulation in purine metabolism, energy metabolism, vitamin B6 pathways, and redox homeostasis. Key metabolites including guanosine monophosphate, adenosine triphosphate, pyridoxal 5\u2032-phosphate, and L-glutathione were markedly restored toward normal levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that NA confers robust neuroprotection in DN by alleviating inflammation and oxidative stress, preserving neuronal structure and function, and reprogramming key metabolic pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1721486","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:54Z","timestamp":1771397814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nervonic acid confers neuroprotection in a zebrafish model of diabetic neuropathy by promoting myelin repair and metabolic modulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Huan","family":"Ge","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University","place":["Hangzhou, China"]},{"name":"Hunter BioInsight Technology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Dai","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Cao","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Guo","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunter Biotechnology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Hunter BioInsight Technology, Inc.","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lushan","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences, Zhejiang University","place":["Hangzhou, China"]},{"name":"Zhejiang Provincial Engineering Research Center for Innovative Small-Molecule Drugs","place":["Jinhua, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"115734","DOI":"10.1016\/j.biopha.2023.115734","article-title":"Diabetes mellitus: classification, mediators, and complications; a gate to identify potential targets for the development of new effective treatments","volume":"168","author":"Antar","year":"2023","journal-title":"Biomed. 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