Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca2+ mobilization

Mast cells play a key role in the pathogenesis of asthma and are a promising target for therapeutic intervention in asthma. This study investigated the effects of polydatin (PD), a resveratrol glucoside, on mast cell degranulation upon cross-linking of the high-affinity IgE receptors (FcεRI), as well as the anti-allergic activity of PD in vivo. Herein, we demonstrated that PD treatment for 30min suppressed FcεRI-mediated mast cell degranulation in a dose-dependent manner. Concomitantly, PD significantly decreased FcεRI-mediated Ca2+ increase in mast cells. The suppressive effects of PD on FcεRI-mediated Ca2+ increase were largely inhibited by using LaCl3 to block the Ca2+ release-activated Ca2+ channels (CRACs). Furthermore, PD significantly inhibited Ca2+ entry through CRACs evoked by thapsigargin (TG). Knocking down protein expression of Orai1, the pore-forming subunit of CRACs, significantly decreased PD suppression of FcεRI-induced intracellular Ca2+ influx and mast cell degranulation. In a mouse model of mast cell-dependent passive cutaneous anaphylaxis (PCA), in vivo PD administration suppressed mast cell degranulation and inhibited anaphylaxis. Taken together, our data indicate that PD stabilizes mast cells by suppressing FcεRI-induced Ca2+ mobilization mainly through inhibiting Ca2+ entry via CRACs, thus exerting a protective effect against PCA. ► Polydatin can prevent the pathogenesis of passive cutaneous anaphylaxis in mice. ► Polydatin stabilizes mast cells by decreasing FcεRI-mediated degranulation. ► Polydatin suppresses Ca2+ entry through CRAC channels in mast cells.