本文采用的英格恩产品: Entranster-H4000

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

Ruijuan Qi  ¹ , Yuan Kang  ¹ , Ximeng Li  ¹ , Xiaoyu Zhang  ¹ , Yixin Han  ¹ , Runlan Cai  ¹ , Yuan Gao  ¹ , Yun Qi  ¹ Affiliations

• PMID: 34194333
• PMCID: PMC8237228
• DOI: 10.3389/fphar.2021.696729

Free PMC article

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.

Keywords: IgE; Mrgpr; cytosolic Ca2+; forsythiae fructus; mast cell degranulation; mitochondrial Ca2+.