title: Inhibitory effect of oblongifolin C on allergic inflammation through the suppression of mast cell activation.
abstract: Oblongifolin C (OC), a natural small molecule compound extracted from Garcinia yunnanensis Hu, has been previously shown to have anti-cancer effect, but the anti-allergic effect of OC has not yet been investigated. The aim of the present study is to determine the anti-allergic effect of OC on IgE/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and on the passive systemic anaphylaxis (PSA) reaction in mice. OC clearly suppressed cyclooxygenase-2 (COX-2)-dependent prostaglandin D2 (PGD2) generation as well as leukotriene C4 (LTC4) generation and the degranulation reaction in IgE/Ag-stimulated BMMCs. Biochemical analyses of the IgE/Ag-mediated signaling pathways showed that OC suppressed the phosphorylation of phospholipase Cγ1 (PLCγ1)-mediated intracellular Ca(2+) influx and the nuclear factor-κB (NF-κB) pathway, as well as the phosphorylation of mitogen-activated protein (MAP) kinases. Although OC did not inhibit the phosphorylation of Fyn, Lyn, and Syk, it directly inhibited the tyrosine kinase activity in vitro. Moreover, oral administration of OC inhibited the IgE-induced PSA reaction in a dose-dependent manner. Taken together, the present study provides new insights into the anti-allergic activity of OC, which could be a promising candidate for allergic therapy.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Shuangfan
authors.initials: S
authors.lastname: Cai
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.forename: Wenwei
authors.initials: W
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006967:Hypersensitivity / Q000188:drug therapy; D017997:Leukotriene C4 / Q000096:biosynthesis; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D013729:Terpenes; C575447:oblongifolin C; D017997:Leukotriene C4; D015230:Prostaglandin D2; D002118:Calcium