title: The Three-Herb Formula Shuang-Huang-Lian stabilizes mast cells through activation of mitochondrial calcium uniporter.
abstract: Mast cells (MCs) are key effector cells of IgE-FcεRI- or MrgprX2-mediated signaling event. Shuang-Huang-Lian (SHL), a herbal formula from Chinese Pharmacopoeia, has been clinically used in type I hypersensitivity. Our previous study demonstrated that SHL exerted a non-negligible effect on MC stabilization. Herein, we sought to elucidate the molecular mechanisms of the prominent anti-allergic ability of SHL. MrgprX2- and IgE-FcεRI-mediated MC activation in vitro and in vivo models were developed by using compound 48/80 (C48/80) and shrimp tropomyosin (ST), respectively. Our data showed that SHL markedly dampened C48/80- or ST-induced MC degranulation in vitro and in vivo. Mechanistic study indicated that cytosolic Ca2+(Ca2+[c]) level decreased rapidly and sustainably after SHL treatment, and then returned to homeostasis when SHL was withdrawn. Moreover, SHL decreases Ca2+[c]levels mainly through enhancing the mitochondrial Ca2+(Ca2+[m]) uptake. After genetically silencing or pharmacologic inhibiting mitochondrial calcium uniporter (MCU), the effect of SHL on the Ca2+[c]level and MC degranulation was significantly weakened. Simultaneously, the activation of SHL on Ca2+[m]uptake was completely lost. Collectively, by activating MCU, SHL decreases Ca2+[c]level to stabilize MCs, thus exerting a remarkable anti-allergic activity, which could have considerable influences on clinical practice and research.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.|Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Hou
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Fei
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Runlan
authors.initials: R
authors.lastname: Cai
authors.affiliation: Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 100193, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qi
mesh_terms: D000485:Allergens / Q000378:metabolism; D018926:Anti-Allergic Agents / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D015550:Cell Degranulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology*; D010935:Plant Diseases
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D015220:Calcium Channels; D004365:Drugs, Chinese Herbal; C034703:mitochondrial calcium uniporter; C516400:shuang-huang-lian; D002118:Calcium