title: Pycnogenol Ameliorates Asthmatic Airway Inflammation and Inhibits the Function of Goblet Cells.
abstract: Pycnogenol®(PYC) is utilized in the treatment of various diseases ranging from chronic inflammation to circulatory diseases, but its efficacy and functional mechanism in pediatric asthma continue to remain obscure. Therefore, the purpose of this study was to investigate the effectiveness and molecular mechanism of PYC on regulation of asthmatic airway inflammation. We found that PYC with tail intravenous injection of 50 mg/kg or intragastric administration of 100 mg/kg all reduced ovalbumin (OVA)-induced airway injury. Pharmacokinetics of PYC was evaluated by high-performance liquid chromatography assay, indicating that PYC was quickly absorbed into the blood after intragastric administration, and PYC metabolism was later improved gradually with increase of time after PYC administration. PYC has a higher bioavailability of 71.96%, and it was more easily absorbed by the body. PYC inhibited the number of total inflammatory cells and levels of interleukin (IL)-4, IL-5, IL-9, and IL-13 in bronchoalveolar lavage fluid of OVA-induced mice. PYC inhibited IL-13 secretion from the Th2 cells, thereby causing a reduction in expression of the signaling molecules in JAK/STAT6 pathway in airway epithelial cells. STAT6 silence suppressed IL-13-increased acetylcholine level. STAT6 overexpression promoted expression of goblet cell metaplasia-associated molecules (FOXA3, SPDEF, and Muc5ac). PYC suppressed OVA-induced expression of FOXA3, SPDEF, and Muc5ac in lung. Our findings indicate that PYC has a higher bioavailability and it prevents emergence of OVA-induced airway injury and airway inflammation in mice by inhibiting IL-13/JAK/STAT6 pathway and blocking release of acetylcholine to reduce goblet cell metaplasia.
authors.affiliation: 1 Department of Neonatology, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong, People's Republic of China .
authors.forename: Zhaoe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 2 Department of Pediatrics, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong, People's Republic of China .
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.affiliation: 2 Department of Pediatrics, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong, People's Republic of China .
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: 3 Department of Neonatal, Maternity and Child Care Hospital , Jinan, Shandong, People's Republic of China .
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 1 Department of Neonatology, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong, People's Republic of China .
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.affiliation: 1 Department of Neonatology, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong, People's Republic of China .
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D020397:Goblet Cells / Q000166:cytology* / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000378:metabolism; D010936:Plant Extracts
chemical_list: D005419:Flavonoids; D018793:Interleukin-13; D010936:Plant Extracts; C024070:pycnogenols; D010047:Ovalbumin
keywords: airway inflammation; goblet cell; pediatric asthma