title: Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation.
abstract: BACKGROUND
  This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured.
  
  
  METHODS
  LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin.Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund's adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy.
  
  
  RESULTS
  XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT.
  
  
  CONCLUSIONS
  XQLT alleviated allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice by regulating neurotrophin and reducing TARC. These results revealed the potential pharmacological targets on which the XQLT decotion exerts preventive and therapeutic effects in an allergic asthma mouse model.
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, No, 91 Hsueh-Shih Road, Taichung 40402, Taiwan. stkao@mail.cmu.edu.tw.
authors.forename: Ren-Shiu
authors.initials: RS
authors.lastname: Chang
authors.forename: Shulhn-Der
authors.initials: SD
authors.lastname: Wang
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Wang
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lin
authors.forename: Shung-Te
authors.initials: ST
authors.lastname: Kao
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000032:analysis / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000378:metabolism*
chemical_list: D039741:Antigens, Dermatophagoides; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D007074:Immunoglobulin G; D020011:Protective Agents; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C090832:sho-seiryu-to; D020932:Nerve Growth Factor