A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

作者：Akram Muhammad; Shin Iljin; Kim Kyeong A; Noh Dabi; Baek Seung Hoon; Chang Sun Young; Kim Hyoungsu; Bae Ok Nam

来源：Toxicology and Applied Pharmacology, 2016, 307: 62-71.

DOI：10.1016/j.taap.2016.07.013

• Synthetic flavonoid
• Anti-inflammatory activity
• TPA-induced acute inflammation
• Oxazolone-induced atopic dermatitis

Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-gamma/TNF-alpha-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC50 for NO inhibition in macrophages: 4.61 mu M). Attenuated NF-kappa B signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPD 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation.

• 出版日期2016-9-15