{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:22:44Z","timestamp":1791948164789,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T00:00:00Z","timestamp":1559001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A2B4004155 and NRF-2017R1C1B3002626"],"award-info":[{"award-number":["NRF-2017R1A2B4004155 and NRF-2017R1C1B3002626"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The skin is an important physiological barrier against external stimuli, such as ultraviolet radiation (UV), xenobiotics, and bacteria. Dermal inflammatory reactions are associated with various skin disorders, including chemical-induced irritation and atopic dermatitis. Modulation of skin inflammatory response is a therapeutic strategy for skin diseases. Here, we synthesized chrysin-derivatives and identified the most potent derivative of Compound 6 (CPD 6). We evaluated its anti-inflammatory effects in vitro cells of macrophages and keratinocytes, and in vivo dermatitis mouse models. In murine macrophages stimulated by lipopolysaccharide (LPS), CPD 6 significantly attenuated the release of inflammatory mediators such as nitric oxide (NO) (IC50 for NO inhibition: 3.613 \u03bcM) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN-\u03b3 and TNF-\u03b1, UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NF\u03baB and JAK2\/STAT1 signaling pathways, and activated Nrf2\/HO-1 signaling. In vivo relevancy of anti-inflammatory effects of CPD 6 was observed in acute and chronic skin inflammation models in mice. CPD 6 showed significant anti-inflammatory properties both in vitro cells and in vivo dermatitis animal models, mediated by the inhibition of the NF\u03baB and JAK2-STAT1 pathways and activation of Nrf2\/HO-1 signaling. We propose that the novel chrysin-derivative CPD 6 may be a potential therapeutic agent for skin inflammation.<\/jats:p>","DOI":"10.3390\/ijms20112607","type":"journal-article","created":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T11:18:09Z","timestamp":1559042289000},"page":"2607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation"],"prefix":"10.3390","volume":"20","author":[{"given":"Chan-Hee","family":"Yu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beomseon","family":"Suh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iljin","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jun","family":"Shin","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7336-9245","authenticated-orcid":false,"given":"Sun-Young","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hoon","family":"Baek","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2774-8727","authenticated-orcid":false,"given":"Hyoungsu","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-2116","authenticated-orcid":false,"given":"Ok-Nam","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Hanyang University, Ansan 15588, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0140-6736(91)92168-2","article-title":"Keratinocytes as initiators of inflammation","volume":"337","author":"Barker","year":"1991","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Carvajal-Vidal, P., Mallandrich, M., Garcia, M.L., and Calpena, A.C. 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