| Summary: | Thymic stromal lymphopoietin (TSLP) plays an important role in the pathophysiology of various allergic diseases that are mediated by T helper cell type-2 (Th2) responses, including asthma and atopic dermatitis. The primary focus of this study was the identification of potent inhibitors of the TSLP signaling pathway for potential therapeutic use. The 80% methanol extract of <i>Machilus thunbergii</i> bark significantly inhibited the signal transducer and activator of transcription 5 (STAT5) phosphorylation in human mast cell (HMC)-1 cells. Through activity-guided isolation, three lignans (<b>1</b>–<b>3</b>) were obtained and identified as (+)-galbelgin (<b>1</b>), <i>meso</i>-dihydroguaiaretic acid (<b>2</b>), and machilin A (<b>3</b>). Among them, two lignans (<b>1</b> and <b>2</b>) significantly inhibited STAT5 phosphorylation and TSLP/TSLPR interaction, as determined by ELISA. Our results indicated that lignans isolated from <i>M. thunbergii</i> are a promising resource for the treatment of allergic diseases.
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