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We investigated the effects of honokiol, a phytochemical found in plants of the genus<jats:italic>Magnolia<\/jats:italic>, on UVB-induced immunosuppression using contact hypersensitivity (CHS) as a model in C3H\/HeN mice. Topical application of honokiol (0.5 and 1.0\u2009mg\/cm<jats:sup>2<\/jats:sup>skin area) had a significant preventive effect on UVB-induced suppression of the CHS response. The inflammatory mediators, COX-2 and PGE<jats:sub>2<\/jats:sub>, played a key role in this effect, as indicated by honokiol inhibition of cyclooxygenase-2 (COX-2) expression and PGE<jats:sub>2<\/jats:sub>production in the UVB-exposed skin. Honokiol application also inhibited UVB-induced DNA hypermethylation and its elevation of the levels of TET enzyme, which is responsible for DNA demethylation in UVB-exposed skin. This was consistent with the restoration of the CHS response in mice treated with the DNA demethylating agent, 5-aza-2\u2032-deoxycytidine, after UVB exposure. There was no significant difference in the levels of inhibition of UVB-induced immunosuppression amongst mice that were treated topically with available anti-cancer drugs (imiquimod and 5-fluorouracil). This study is the first to show that honokiol has the ability to inhibit UVB-induced immunosuppression in preclinical model and, thus, has potential for use as a chemopreventive strategy for UVB radiation-induced malignancies.<\/jats:p>","DOI":"10.1038\/s41598-017-01774-5","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T10:03:43Z","timestamp":1493892223000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Honokiol inhibits ultraviolet radiation-induced immunosuppression through inhibition of ultraviolet-induced inflammation and DNA hypermethylation in mouse skin"],"prefix":"10.1038","volume":"7","author":[{"given":"Ram","family":"Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripti","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh K.","family":"Katiyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,10]]},"reference":[{"key":"1774_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2007.02.010","volume":"255","author":"SK Katiyar","year":"2007","unstructured":"Katiyar, S. 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