Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation

• Published in: International journal of molecular sciences Vol. 20; no. 11; p. 2607
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.05.2019; MDPI
• Subjects: Animal models; Anti-inflammatory agents; Atopic dermatitis; Chemical compounds; Chemical reactions; chrysin; chrysin derivatives; Cytokines; Dermatitis; External stimuli; Inflammation; Inflammatory response; Irritation; Janus kinase 2; Keratinocytes; Kinases; Lipopolysaccharides; Macrophages; NF-κB protein; Nitric oxide; Nrf2/HO-1 signaling; Organic chemistry; Pharmacology; Rodents; Signal transduction; Skin diseases; skin inflammation; Stat1 protein; synthetic flavonoid; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ultraviolet radiation; Xenobiotics; γ-Interferon; Nrf2/HO-1 signaling; synthetic flavonoid; chrysin; chrysin derivatives; skin inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20112607

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) (IC for NO inhibition: 3.613 μM) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN-γ and TNF-α, UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NFκB 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 NFκB 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.