title: Anti-allergic and anti-inflammatory properties of a potent histamine H1 receptor antagonist, desloratadine citrate disodium injection, and its anti-inflammatory mechanism on EA.hy926 endothelial cells.
abstract: The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-κB) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression.
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jie
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Nandani Darshika
authors.initials: ND
authors.lastname: Kodithuwakku
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Hefei Yigong Medicine Co., Ltd, Hefei 230088, Anhui, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China. Electronic address: wylcpu625@163.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D002470:Cell Survival; D002744:Chlorpheniramine / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D012220:Rhinitis / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D002744:Chlorpheniramine; D017336:Loratadine; D006632:Histamine; C121345:desloratadine
keywords: Anti-allergic; Anti-inflammatory; Antihistamine; Chlorpheniramine maleate (PubChem CID: 5281068); Desloratadine citrate disodium injection; EA.hy926 endothelial cells; Histamine (PubChem CID: 774); Lipopolysaccharide (PubChem CID: 11970143)