Screening anti‐anaphylactoid components in Polygonum cuspidatum via cell membrane chromatography with LC‐MS targeting Mas‐related G protein‐coupled receptor X2

Mas‐related G protein‐coupled receptor X2 (MrgprX2) is acknowledged as a mast cell‐specific receptor, playing a crucial role in orchestrating anaphylactoid responses through mast cell degranulation. It holds promise as a target for regulating allergic and inflammatory diseases mediated by mast cells. Polygonum cuspidatum (PC) has shown notable anti‐anaphylactoid effects, while its pharmacologically active components remain unclear. In this study, we successfully utilized MrgprX2 high‐expressing cell membrane chromatography (CMC), in conjunction with liquid chromatography‐mass spectrometry (LC‐MS), to identify active anti‐anaphylactoid components in PC. Our study pinpointed polydatin, resveratrol, and emodin‐8‐O‐β‐ d ‐glucoside as potential anti‐anaphylactoid compounds in PC. Their anti‐anaphylactoid activities were evaluated through β‐aminohexosidase and histamine release assays, demonstrating a concentration‐dependent inhibition for both β‐aminohexosidase and histamine release. This approach, integrating MrgprX2 high‐expression CMC with LC‐MS, proves effective in screening potential anti‐anaphylactoid ingredients in natural herbal medicines. The findings from this study illuminated the anti‐anaphylactoid properties of specific components in PC and provided an efficient method for the drug development of natural products.