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(NIH)","award":["RG-2206-39711"],"award-info":[{"award-number":["RG-2206-39711"]}]},{"name":"National Institutes of Health (NIH)","award":["P51 OD011092"],"award-info":[{"award-number":["P51 OD011092"]}]},{"name":"National Institutes of Health (NIH)","award":["T32 AG055378"],"award-info":[{"award-number":["T32 AG055378"]}]},{"name":"National Institutes of Health (NIH)","award":["T32 ES007060"],"award-info":[{"award-number":["T32 ES007060"]}]},{"name":"National Institutes of Health (NIH)","award":["RF1 AG059088"],"award-info":[{"award-number":["RF1 AG059088"]}]},{"name":"National Institutes of Health (NIH)","award":["R21 AG065914"],"award-info":[{"award-number":["R21 AG065914"]}]},{"name":"National Institutes of Health (NIH)","award":["R21 AG079158-01A1"],"award-info":[{"award-number":["R21 AG079158-01A1"]}]},{"name":"National Institutes of Health (NIH)","award":["NIH\/NCCIH U19 AT010829"],"award-info":[{"award-number":["NIH\/NCCIH U19 AT010829"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives:\u00a0Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL\/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS.<\/jats:p>","DOI":"10.3390\/ph17121681","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T03:51:08Z","timestamp":1734061868000},"page":"1681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Centella asiatica Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis"],"prefix":"10.3390","volume":"17","author":[{"given":"Payel","family":"Kundu","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanon","family":"Yasuhara","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University (OHSU), Beaverton, OR 97006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikah S.","family":"Brandes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Zweig","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody J.","family":"Neff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Holden","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kat","family":"Kessler","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Integrative Biosciences, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halina","family":"Offner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"Neurology Division, Portland VA Medical Center, Portland, OR 97239, USA"},{"name":"Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-0599","authenticated-orcid":false,"given":"Carin S.","family":"Waslo","sequence":"additional","affiliation":[{"name":"Neurology Division, Portland VA Medical Center, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1207-6817","authenticated-orcid":false,"given":"Arthur","family":"Vandenbark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"Neurology Division, Portland VA Medical Center, Portland, OR 97239, USA"},{"name":"Department of Molecular Microbiology and Immunology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-6453","authenticated-orcid":false,"given":"Amala","family":"Soumyanath","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-6551","authenticated-orcid":false,"given":"Larry S.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University (OHSU), Beaverton, OR 97006, USA"},{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-9893","authenticated-orcid":false,"given":"Jacob","family":"Raber","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University (OHSU), Beaverton, OR 97006, USA"},{"name":"Department of Neurology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"},{"name":"Department of Radiation Medicine, Oregon Health & Science University (OHSU), Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora E.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon 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