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Mast cells (MCs) activated via IgE/FcεRI or MAS-related G protein coupled receptor (Mrgpr)-mediated pathway can release granules that play prominent roles in hypersensitivity reactions. Forsythiae Fructus, a well-known traditional Chinese medicine, has been clinically used for allergic diseases. Although previous studies indicated that Forsythiae Fructus extract inhibited compound 48/80-induced histamine release from MCs, its effect on IgE-dependent MC degranulation and possible underlying mechanisms remain to be explored. Herein, we prepared the forsythiasides-rich extract (FRE) and investigated its action on MC degranulation and explored its underlying mechanism. Our data showed that FRE could dampen IgE/FcεRI- and Mrgpr-mediated MC degranulation  in vitro  and  in vivo . Mechanism study indicated that FRE decreased cytosolic Ca 2+  (Ca 2+   [c] ) level rapidly and reversibly. Moreover, FRE decreased Ca 2+   [c]  of MCs independent of plasma membrane Ca 2+ -ATPase (PMCA), sarco/endoplasmic Ca 2+ -ATPase (SERCA) and Na + /Ca 2+  exchanger (NCX). While, along with Ca 2+   [c]  decrease, the increase of mitochondrial Ca 2+  (Ca 2+   [m] ) occurred simultaneously in FRE-treated RBL-2H3 cells. In the isolated mitochondria, FRE also promoted the subcellular organelle to uptake more extramitochondrial Ca 2+ . In conclusion, by increasing Ca 2+   [m]  uptake, FRE decreases Ca 2+   [c]  level to suppress MC degranulation. Our findings may provide theoretical support for the clinical application of Forsythiae Fructus on allergy and other MC-involved diseases.

Forsythiasides-Rich Extract From Forsythiae Fructus Inhibits Mast Cell Degranulation by Enhancing Mitochondrial Ca2+ Uptake