Development of PPAR Regulators
의약학 > 해부학
( Yun Hee Chang ) , ( Sang Hwa Lee )
한국피부장벽학회지 2012년, 제14권 제2호, 56~64쪽(총9쪽)
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    Peroxisome proliferator-activated receptor (PPAR) is a family of nuclear hormone receptor and plays important roles in skin barrier homeostasis by regulating epidermal cell growth, terminal keratinocyte differentiation, and inflammatory responses. Among three PPAR isotypes, topically applied PPARα activators have pleotropic effects on skin such as anti-proliferative/ pro-differentiating, anti-inflammatory, and acceleration of skin barrier recovery. All these observations suggest that PPARα activators hold great promise for therapy of cutaneous skin disease. To identify medicinal herbs that contain PPARα activators, GAL4-PPARα transactivation assay was used. It was found that the non-polar fraction of Zanthoxylum bungeanum extract had a potent PPARα activating activity which is even higher than clofibrate, a well-known PPARα agonist used for pharmaceutical drug. Expression of keratinocyte differentiation markers such as transglutaminse and involucrin was increased in cultured keratinocytes treated with Z. bungeanum extract. In an in vitro inflammation model with ultraviolet B light-irradiated keratinocytes, Z. bungeanum extract decreased the secretion of tumor necrosis factor-α, one of the major cutaneous inflammatory cytokines, from keratinocytes. Its anti-inflammatory effect was further demonstrated by in vivo testing in which topical application of Z. bungeanum extract markedly decreased the ear thickness of the 12-O-tetradecanolyphorbol-12-acetate treated mice. Topical application of Z. bungeanum extract increased the expression of keratinocyte differentiation markers, involucrin and filagrrin in hairless mouse skin. It markedly accelerated the repair rate of skin barrier function as measured by TEWL in hairless mouse skin whose barrier function was disrupted by tape stripping. We isolated and determined 3-linoleoyl-rac-glycerol, as an active compound of Hyoscyamus niger extract, another natural PPARα activator we have found. These results suggest that the extract of Zanthoxylum bungeanum could be developed as a potential therapeutic agent for the regulation of skin barrier homeostasis by activating PPARα.
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