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
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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