Study on the mechanisms of the bronchodilator effects of Folium Eriobotryae and the selected active ingredient on isolated guinea pig tracheal strips

Abstract

Context: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. Materials and 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 CaCl2 curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ. Discussion and conclusion: 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.