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Honokiol (HNK) is a bioactive compound known for its medicinal properties. This study evaluated HNK\u2019s effectiveness in alleviating pain, depression, and anxiety in a reserpine-induced FM rat model. Thirty male rats were divided into three groups: control, RES (FM-induced), and RES\u2009+\u2009HNK. HNK was supplemented to RES\u2009+\u2009HNK in a dose of 8\u00a0mg\/kg for 21 days. Behavioral assessments included the open field, elevated plus maze, and forced swim tests, while pain was evaluated using treadmill endurance, tail flick latency, paintbrush, and rotarod tests. Brain homogenates were analyzed for neurotransmitters, antioxidants, pro-inflammatory cytokines, and gene expressions. Histopathological evaluation of spinal cords assessed markers of inflammation and apoptosis. Results showed that HNK administration improved behavior and reduced pain. This was linked to reduced levels of malondialdehyde, tumor necrosis factor-\u03b1, and prostaglandin E2, alongside increased superoxide dismutase and interleukin-10. Additionally, HNK downregulated the expression of calcitonin gene-related peptide and the JAK\/STAT3 gene. These findings suggest that HNK alleviates FM symptoms through its antioxidant, anti-inflammatory, neuroprotective, and anti-apoptotic properties, indicating its potential as a therapeutic agent for FM.<\/jats:p>","DOI":"10.1038\/s41598-025-07209-w","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T18:24:01Z","timestamp":1752776641000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Honokiol ameliorates reserpine-induced fibromyalgia through antioxidant, anti-inflammatory, neurotrophic, and anti-apoptotic mechanisms"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-9445","authenticated-orcid":false,"given":"Suzan A.","family":"Khodir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3689-2648","authenticated-orcid":false,"given":"Eman M.","family":"Sweed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9938-3907","authenticated-orcid":false,"given":"Hala","family":"El-Haroun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek H.","family":"Abd-Elhamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2659-9328","authenticated-orcid":false,"given":"Sara A.","family":"El Derbaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany R.","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-6541","authenticated-orcid":false,"given":"Shaimaa M.","family":"Motawea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"7209_CR1","doi-asserted-by":"publisher","unstructured":"Siracusa, R., Paola, R. 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