Forsythiasides-Rich Extract From Forsythiae Fructus Inhibits Mast Cell Degranulation by Enhancing Mitochondrial Ca(2+) Uptake

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.