title: Study on the mechanisms of the bronchodilator effects of Folium Eriobotryae and the selected active ingredient on isolated guinea pig tracheal strips.
abstract: BACKGROUND
  Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders.
  
  
  OBJECTIVE
  To examine the bronchodilatory activity of FE and the potential mechanisms involved.
  
  
  METHODS
  The effects of ethyl acetate fraction of FE (EFE) (0.05-0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5-30 μg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors.
  
  
  RESULTS
  With in vitro studies, the contractile response evoked by Ach or His (EC50=0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration-dependent relaxation precontracted by His (EC50=23.2 μg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 μM), NG-nitro-l-arginine methyl ester (l-NAME) (100 μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 μM). EFE also inhibited the contraction in Ca2+-free medium and produced rightward parallel displacement of CaCl2curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ.
  
  
  CONCLUSIONS
  These results suggest that bronchodilator activities of EFE were related to activation of β-adrenoceptor and NO/cGMP pathway. Blockage of Ca2+channels and inhibition of IP3R-mediated internal Ca2+release were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway.
authors.affiliation: a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: b Department of Pharmacy , Logistics University of Chinese People's Armed Police Forces , Tianjin , China.
authors.forename: Jingze
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Qu
authors.affiliation: c Traditional Chinese Medicine Factory , Tianjin Zhongxin Pharmaceutical Group Corporation Ltd , Tianjin , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: c Traditional Chinese Medicine Factory , Tianjin Zhongxin Pharmaceutical Group Corporation Ltd , Tianjin , China.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Tong
authors.affiliation: c Traditional Chinese Medicine Factory , Tianjin Zhongxin Pharmaceutical Group Corporation Ltd , Tianjin , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.
authors.forename: Honggai
authors.initials: H
authors.lastname: Yang
authors.affiliation: a Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D031983:Eriobotrya / Q000737:chemistry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D001993:Bronchodilator Agents; D002118:Calcium; D000242:Cyclic AMP; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D010069:Oxadiazoles; D010936:Plant Extracts; D011810:Quinoxalines; D014315:Triterpenes; D000097245:Ursolic Acid; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
keywords: Asthma; calcium channel; nitric oxide; ursolic acid; β-adrenoceptor