title: The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma.
abstract: Mast cells play an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. The genus Garcinia of the family Guttiferae is well known as a prolific source of polycyclic polyprenylated acylphloroglucinols and bioactive prenylated xanthones, which exhibit various biological activities including antibacterial, antifungal, anti-inflammatory, antioxidant, and cytotoxic effects. Nujiangexanthone A (N7) is a novel compound isolated from the leaves of Garcinia nujiangensis. In this paper, we sought to determine the anti-allergic and anti-inflammation activity of N7 in vivo and its mechanism in vitro. We found N7 suppressed IgE/Ag induced mast cell activiation, including degranulation and production of cytokines and eicosanoids, through inhibiting Src kinase activity and Syk dependent pathways. N7 inhibited histamine release, prostaglandin D2 and leukotriene C4 generation in mast cell dependent passive cutaneous anaphylaxis animal model. We also found N7 inhibited the IL-4, IL-5, IL-13 and IgE levels in ovalbumin-induced asthma model. Histological studies demonstrated that N7 substantially inhibited OVA-induced cellular infiltration and increased mucus production in the lung tissue. Our study reveals the anti-allergic function of N7, thereby suggesting the utility of this compound as a possible novel agent for preventing mast cell-related immediate and delayed allergic diseases.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
authors.forename: Shuangfan
authors.initials: S
authors.lastname: Cai
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200030, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Nie
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200030, PR China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pneumology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Guochao
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Pneumology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Jimin
authors.initials: J
authors.lastname: Hao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200030, PR China. Electronic address: binli@sibs.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, PR China. Electronic address: xuhongxi88@gmail.com.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D029760:Garcinia; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018926:Anti-Allergic Agents; D010936:Plant Extracts
keywords: Asthma; Dexamethasone (PubChem CID: 5743); Mast cell; Nujiangexanthone A; PP2 (PubChem CID: 4878); Syk