title: Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca²⁺ mobilization.
abstract: 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 30 min 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.
authors.affiliation: Department of Pathophysiology, School of Medicine, Shenzhen University, Shenzhen 518060, China.
authors.forename: Meichun
authors.initials: M
authors.lastname: Yuan
authors.forename: Jianjie
authors.initials: J
authors.lastname: Li
authors.forename: Jingzhang
authors.initials: J
authors.lastname: Lv
authors.forename: Xucheng
authors.initials: X
authors.lastname: Mo
authors.forename: Chengbin
authors.initials: C
authors.lastname: Yang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000502:physiology*; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D017382:Reactive Oxygen Species; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; C543355:FcepsilonRI alpha-chain, human; D005960:Glucosides; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D013267:Stilbenes; D007073:Immunoglobulin E; D002118:Calcium; C058229:polydatin