{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:34:05Z","timestamp":1784806445795,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education Research Grant","award":["FRGS\/1\/2021\/SKK0\/UKM\/02\/12"],"award-info":[{"award-number":["FRGS\/1\/2021\/SKK0\/UKM\/02\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Persistent and chronic hyperglycaemia in Type II diabetic mellitus (DM) is known to cause oxidative stress, which exacerbates underlying metabolic disorders, contributing to the progression of complications such as diabetic peripheral neuropathy (DPN). Palm tocotrienol-rich fraction (TRF) is renowned for its potent antioxidative and neuroprotective properties and might have the potential to halt or mitigate the severity of DPN. This study aimed to investigate the effects of palm TRF on diabetic rats with peripheral neuropathy and to identify the correlation between plasma metabolomic alterations and DPN parameters. Male Sprague Dawley (SD) rats were randomly divided into normal control and DM groups in which Type II DM was induced using a high-fat diet and a low-dose streptozotocin (STZ) (35 mg\/kg). Successful diabetic rats were randomly divided and received daily oral treatments of palm olein (vehicle), metformin (70 mg\/kg), TRF (60 mg\/kg), or a combination of TRF and metformin for 12 weeks. Behavioural parameters, serum biomarkers, and plasma metabolomic profiling were assessed at 0 (baseline) and 12 weeks of intervention. From the behavioural parameters, improvement in the symptoms of thermal hyperalgesia and mechanical allodynia was seen with TRF interventions, either alone or in combination with metformin. A significant reduction in the neurofilament light (NEFL) chain, accompanied by a notable increase in nerve growth factor (NGF) levels in the serum of treatment groups, was also observed. From the plasma samples, findings reveal that TRF increases metabolites related to neurotransmitter pathways (acetylcholine, choline, phenylalanine, tryptophan) and decreases inflammatory metabolites (kynurenine, prostaglandin) compared to untreated diabetic rats. These metabolites, except for prostaglandin, showed positive correlations with pain sensitivity. In contrast, prostaglandin showed opposite correlations with pain and nerve damage markers, suggesting its potential role in inflammation and axonal injury.<\/jats:p>","DOI":"10.3390\/ijms262311247","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:59:46Z","timestamp":1763715586000},"page":"11247","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Effects of Palm Tocotrienol-Rich Fraction in Diabetic Peripheral Neuropathy Rat\u2019s Model: An Untargeted Metabolomic Profiling and Correlation Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9719-6662","authenticated-orcid":false,"given":"Noradliyanti","family":"Rusli","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-0581","authenticated-orcid":false,"given":"Jen Kit","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Makpol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"},{"name":"Ageing and Degenerative Diseases Research Group, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-9927","authenticated-orcid":false,"given":"Isma Liza","family":"Mohd Isa","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"},{"name":"C\u00daRAM Research Ireland Centre for Medical Devices, School of Medicine, University of Galway, H91 TK33 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Haleeda","family":"Hakimi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazirah","family":"Ab Rani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-7609","authenticated-orcid":false,"given":"Rabani","family":"Remli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2019","journal-title":"J. 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