Isoegomaketone Ameliorates Atopic Dermatitis via MAPK and STAT Pathway-based Pro-Inflammatory Cytokine Regulation
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Isoegomaketone (IK), isolated from the radiation-induced mutant cultivar of Perilla frutescensvar. crispa, is a major phytochemical compound that has attracted attention in pharmacological research. In this study, we demonstrated that IK exerts anti-inflammatory and protective effects on human mastcells and in an atopic dermatitis mouse model. IK inhibited tumor necrosis factor-α (TNF-α), interleukin-6(IL-6), and IL-8 expression in human mast cells (HMC-1) stimulated with phorbol myristate acetate (PMA)and calcium ionophore A23187 (PMACI). IK significantly reduced the PMACI-induced phosphorylation ofERK and JNK, but not p38. IK also inhibited the PMACI-induced phosphorylation of STAT1 and STAT3. Oral administration of IK in atopic dermatitis mouse model ameliorated skin inflammation severity, asmeasured by skin thickness and pro-inflammatory cytokine levels such as TNF-α, IL-8, IL-4, and IL-13. These results might suggest that IK is a potent therapeutic agent against skin inflammation and atopicdermatitis.
Abstract
Isoegomaketone (IK), isolated from the radiation-induced mutant cultivar of Perilla frutescensvar. crispa, is a major phytochemical compound that has attracted attention in pharmacological research. In this study, we demonstrated that IK exerts anti-inflammatory and protective effects on human mastcells and in an atopic dermatitis mouse model. IK inhibited tumor necrosis factor-α (TNF-α), interleukin-6(IL-6), and IL-8 expression in human mast cells (HMC-1) stimulated with phorbol myristate acetate (PMA)and calcium ionophore A23187 (PMACI). IK significantly reduced the PMACI-induced phosphorylation ofERK and JNK, but not p38. IK also inhibited the PMACI-induced phosphorylation of STAT1 and STAT3. Oral administration of IK in atopic dermatitis mouse model ameliorated skin inflammation severity, asmeasured by skin thickness and pro-inflammatory cytokine levels such as TNF-α, IL-8, IL-4, and IL-13. These results might suggest that IK is a potent therapeutic agent against skin inflammation and atopicdermatitis.
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