{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:48:29Z","timestamp":1787017709285,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":144,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["7202149"],"award-info":[{"award-number":["7202149"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771998"],"award-info":[{"award-number":["81771998"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["51972339"],"award-info":[{"award-number":["51972339"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Oral mucositis (OM) is a common complication during chemotherapy characterized by ulceration, mucosa atrophy, and necrosis, which seriously interferes with nutritional intake and oncotherapy procedures among patients. However, the efficacy of current treatments for OM remains limited. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including antioxidant and anti\u2010inflammatory potential. In this study, we aimed to investigate the chemopreventive effects and mechanisms of CBD in protecting C57BL\/6N mice and human oral keratinocytes (HOK) from 5\u2010fluorouracil\u2010 (5\u2010FU\u2010) induced OM. Here, we found that CBD alleviated the severity of 5\u2010FU\u2010induced OM in mice, including improved survival, decreased body weight loss, reduced ulcer sizes, and improved clinical scores. Histologically, CBD restored epithelial thickness and normal structure in tongue tissues. Meanwhile, CBD attenuated reactive oxygen species (ROS) overproduction and improved the antioxidant response, suppressed the inflammatory response, promoted the proliferation of epithelial cells, and inhibited 5\u2010FU\u2010induced apoptosis.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , consistent outcomes showed that CBD suppressed cellular ROS levels, enhanced antioxidant ability, reduced inflammatory response, promoted proliferation, and inhibited apoptosis in 5\u2010FU\u2010treated HOK cells. In particular, CBD upregulated the expression levels of antioxidant enzymes, heme oxygenase\u20101 (HO\u20101) and NAD(P)H quinine oxidoreductase 1 (NQO1), by increasing the expression and nuclear translocation of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) and decreasing Kelch\u2010like ECH\u2010associated protein 1 (Keap1). Notably, the Nrf2 inhibitor ML385 reversed the protective effect of CBD. Nrf2\u2010siRNA transfection also significantly blunted the antioxidant effect of CBD in\n                    <jats:italic>in vitro<\/jats:italic>\n                    OM model. Collectively, our findings suggested that CBD protected against 5\u2010FU\u2010induced OM injury at least partially via the Nrf2\/Keap1\/ARE signaling pathways, highlighting the therapeutic prospects of CBD as a novel strategy for chemotherapy\u2010induced OM.\n                  <\/jats:p>","DOI":"10.1155\/2022\/4619760","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T20:20:58Z","timestamp":1653510058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protective Effects of Cannabidiol on Chemotherapy\u2010Induced Oral Mucositis via the Nrf2\/Keap1\/ARE Signaling 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