Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation
Autor: | Hyoungsu Kim, Seung-Hoon Baek, Donghyun Kim, Iljin Shin, Sun-Young Chang, Chan-Hee Yu, Beomseon Suh, Ok-Nam Bae, Eun-Hye Kim, Young-Jun Shin |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Keratinocytes
Male Lipopolysaccharide Anti-Inflammatory Agents Dermatitis Stimulation Pharmacology lcsh:Chemistry Mice chemistry.chemical_compound chrysin Chrysin lcsh:QH301-705.5 Spectroscopy Mice Inbred BALB C Mice Inbred ICR integumentary system Chemistry NF-kappa B chrysin derivatives General Medicine Atopic dermatitis Computer Science Applications STAT1 Transcription Factor Cytokines medicine.symptom NF-E2-Related Factor 2 education Inflammation Nitric Oxide Article Catalysis Nitric oxide Proinflammatory cytokine Inorganic Chemistry In vivo skin inflammation medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology Flavonoids Macrophages Organic Chemistry Janus Kinase 2 medicine.disease synthetic flavonoid RAW 264.7 Cells lcsh:Biology (General) lcsh:QD1-999 Nrf2/HO-1 signaling Dermatologic Agents Heme Oxygenase-1 |
Zdroj: | International Journal of Molecular Sciences, Vol 20, Iss 11, p 2607 (2019) International Journal of Molecular Sciences Volume 20 Issue 11 |
ISSN: | 1422-0067 |
Popis: | 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 &mu M) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN-&gamma and TNF-&alpha UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NF&kappa B 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&kappa B 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. |
Databáze: | OpenAIRE |
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