{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:18:09Z","timestamp":1792113489144,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":228,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Chemotherapy\u2010induced peripheral neuropathy (CIPN) is an adverse event caused by drugs such as bortezomib, vincristine, paclitaxel, and oxaliplatin (L\u2010OHP). This condition can lead to the discontinuation of anticancer drug administration and a diminished quality of life, posing a significant clinical problem. However, the only currently recognized effective treatment is duloxetine, and new therapeutic options are urgently required.\n                    <jats:italic>Lentinula edodes<\/jats:italic>\n                    mycelia extract (LEM) has been reported to improve CIPN in mouse models and alleviate numbness in patients with persistent neuropathy following L\u2010OHP treatment. However, the active ingredients responsible for the attenuation of neuropathy remain unknown. We extracted the fractions from LEM, and an L\u2010OHP\u2010evoked allodynia mouse model was used to investigate which fraction contained the active ingredient. LEM was separated into an ethanol\u2010soluble fraction (LES), an ethanol\u2010insoluble fraction (LEP), and LEM(\u2212), a hot water extract from the LEM\u2010free medium. LEP abolished L\u2010OHP\u2010evoked allodynia, whereas LES and LEM(\u2212) did not. In addition, fractionation of LEP based on molecular weight sieving yielded fractions LEP\u20101 (molecular weight \u2265\u2009100,000) and LEP\u20102 (molecular weight &lt;\u2009100,000), the latter of which was found to inhibit L\u2010OHP\u2010evoked allodynia. Similarly, fractionation of LEP\u20102 gave rise to LEP\u20103 (molecular weight 3500\u201350,000) and LEP\u20104 (molecular weight \u2264\u20093500), the former of which had no inhibitory effects on L\u2010OHP\u2010evoked allodynia, whereas an inhibitory effect was observed in response to the administration of LEP\u20104. In addition, LEP\u20104 was found to abrogate the expression of NR2A and Cav3.2 mRNAs in the dorsal root ganglion (DRG), and inhibited the activation of extracellular regulated\u2010protein kinase 1\/2 (ERK1\/2) in both the spinal cord and DRG. Moreover, oral administration of 0.25\u2009g\/kg LEP\u20104 ameliorated allodynia, which had developed following L\u2010OHP administration. These findings indicate that the active component preventing CIPN in LEM resides in LEP\u20104. This compound has prophylactic and therapeutic potential for L\u2010OHP\u2010evoked allodynia by abrogating NR2A and Cav3.2 mRNA expression and activating ERK1\/2.\n                  <\/jats:p>","DOI":"10.1155\/adpp\/4435116","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:25:50Z","timestamp":1786958750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Ethanol\u2010Insoluble Low\u2010Molecular\u2010Weight Fraction LEP\u20104 Derived From\n                    <i>Lentinula edodes<\/i>\n                    Mycelia Extract Attenuates Oxaliplatin\u2010Evoked Allodynia in 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