AUTHOR=Qi Ruijuan , Kang Yuan , Li Ximeng , Zhang Xiaoyu , Han Yixin , Cai Runlan , Gao Yuan , Qi Yun TITLE=Forsythiasides-Rich Extract From Forsythiae Fructus Inhibits Mast Cell Degranulation by Enhancing Mitochondrial Ca2+ Uptake JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.696729 DOI=10.3389/fphar.2021.696729 ISSN=1663-9812 ABSTRACT=

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 Ca²⁺ (Ca²⁺_[c]) level rapidly and reversibly. Moreover, FRE decreased Ca²⁺_[c] of MCs independent of plasma membrane Ca²⁺-ATPase (PMCA), sarco/endoplasmic Ca²⁺-ATPase (SERCA) and Na⁺/Ca²⁺ exchanger (NCX). While, along with Ca²⁺_[c] decrease, the increase of mitochondrial Ca²⁺ (Ca²⁺_[m]) occurred simultaneously in FRE-treated RBL-2H3 cells. In the isolated mitochondria, FRE also promoted the subcellular organelle to uptake more extramitochondrial Ca²⁺. In conclusion, by increasing Ca²⁺_[m] uptake, FRE decreases Ca²⁺_[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.