{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:44:34Z","timestamp":1782697474099,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal loss. Despite available therapies, there is currently no effective cure for MS. Ibudilast (IBD), a phosphodiesterase inhibitor, and 6-shogaol (SH), a bioactive compound from ginger, have independently shown therapeutic potential in MS models. This study aimed to evaluate the therapeutic efficacy of combining SH and IBD in modulating neuroinflammation and improving functional recovery in a cuprizone (CPZ) mouse model of MS. Methods: Male SWR\/J mice were exposed to 0.3% CPZ for 5 weeks to induce demyelination, followed by 4 weeks of spontaneous remyelination after CPZ withdrawal. During remyelination, the CPZ group was subdivided into four groups: no therapy, SH (25 mg\/kg), IBD (10 mg\/kg), and SH + IBD. Behavioral tests were used to assess locomotion, muscle strength, coordination, and memory. Gene expression of proinflammatory and anti-inflammatory cytokines was analyzed in brain tissue. Results: The combined treatment significantly improved locomotor activity, muscle strength, and memory during remyelination phases while suppressing proinflammatory gene expression and enhancing anti-inflammatory pathways in the brain. Conclusions: SH and IBD combination therapy provides enhanced anti-inflammatory and functional benefits compared with monotherapies, supporting its potential as a promising multi-target therapeutic strategy for improving functional recovery and modulating neuroinflammation during the spontaneous remyelination phase following CPZ withdrawal.<\/jats:p>","DOI":"10.3390\/ph19071004","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effects of Combined 6-Shogaol and Ibudilast on Neuroinflammation and Behavioral Deficits in a Cuprizone Mouse Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7493-7224","authenticated-orcid":false,"given":"Gadah Ali","family":"Alshahrany","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kholoud A.","family":"Alyami","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor Ahmed","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2843-169X","authenticated-orcid":false,"given":"Mohammad Zubair","family":"Alam","sequence":"additional","affiliation":[{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badrah S.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-8476","authenticated-orcid":false,"given":"Ulfat M.","family":"Omar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer A.","family":"Banjabi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3739-8844","authenticated-orcid":false,"given":"Huda F.","family":"Alshaibi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Stem Cell Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana Jamalaldin","family":"Jambi","sequence":"additional","affiliation":[{"name":"The Applied College, Department of Health Information Technology, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-5862","authenticated-orcid":false,"given":"Kholoud M.","family":"Al-Otaibi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha 65799, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8474-8985","authenticated-orcid":false,"given":"Hadeil M.","family":"Alsufiani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi 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