Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammationopen access
- Authors
- Yu, Chan-Hee; Suh, Beomseon; Shin, Iljin; Kim, Eun-Hye; Kim, Donghyun; Shin, Young-Jun; Chang, Sun-Young; Baek, Seung-Hoon; Kim, Hyoungsu; Bae, Ok-Nam
- Issue Date
- Jun-2019
- Publisher
- MDPI
- Keywords
- skin inflammation; synthetic flavonoid; chrysin; chrysin derivatives; Nrf2; HO-1 signaling
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.20, no.11
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 20
- Number
- 11
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/2851
- DOI
- 10.3390/ijms20112607
- ISSN
- 1661-6596
- Abstract
- 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 M) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN- and TNF-, UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NFB 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 NFB 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.
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