title: Selaginella uncinata flavonoids ameliorated ovalbumin-induced airway inflammation in a rat model of asthma.
abstract: BACKGROUND
  Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao", is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries.
  
  
  OBJECTIVE
  This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma.
  
  
  METHODS
  Rats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells.
  
  
  RESULTS
  SUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats.
  
  
  CONCLUSIONS
  These results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma.
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Traditional Chinese Medicine, Zhejiang Pharmaceutical College, Ningbo 315100, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Yu-Sen
authors.initials: YS
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Wen-You
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China; Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Li
authors.initials: L
authors.lastname: Mo
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China; Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors.forename: Lu-Chen
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China. Electronic address: yuchenhuan2002@163.com.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Yu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D050778:NFATC Transcription Factors / Q000378:metabolism; D000071740:ORAI1 Protein / Q000378:metabolism; D010047:Ovalbumin; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D032503:Selaginellaceae / Q000737:chemistry*; D014162:Transfection; D000098706:Taste Receptors, Type 2
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D016207:Cytokines; D005419:Flavonoids; D053496:Inositol 1,4,5-Trisphosphate Receptors; C488910:Itpr1 protein, rat; D050778:NFATC Transcription Factors; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D010936:Plant Extracts; D016271:Proto-Oncogene Proteins c-myc; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Airway hyperresponsiveness; Amentoflavone; Bitter taste receptors; Eotaxin; Th2 cytokines