Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist  

作　　者：Gang BAI Yang YANG Qian SHI Ze LIU Qi ZHANG Yuan-yuan ZHU 

机构地区：[1]College of Life Sciences, Nankai University, Tianjin 300071, China [2]College of Pharmaceutical Sciences, Nankai University, Tianjin 300071, China

出　　处：《Acta Pharmacologica Sinica》2008年第10期1187-1194,共8页中国药理学报（英文版）

基　　金：This work was supported in part by grants from the National High Technology Research and Development Program of China （863 Program） （No 2006AA020502）, and the Natural Science Foundation of Tianjin, China （No 07JCZDJC05000）. Author contribution Gang BAI designed research; Yang YANG, Qian SHI, and Ze LIU performed research; Yuan-yuan ZHU contributed new analytical tools and analyzed data; Qi ZHANG and Yang YANG wrote the paper.

摘　　要：Aim： To screen beta2-adrenergic receptor Lateralis Preparata （RALP） as potential （β2-AR） agonists from Radix Aconiti drug leads for asthma using a sensitive cell-based agonist assay. Methods： The β2-AR gene was stably expressed by Chinese hamster ovary （CHO） cells also stably expressing a cyclic adenosine monophosphate （AMP） response element-linked enhanced green fluorescent protein reporter gene. The cells were used to screen agonists from high-performance liquid chromatographic fractions of an extract of RALE The fraction with the highest activity was selected for further compound isolation and the study of the structure-activity relationship. Its active compound was further identified by chromatography and mass spectrometry. Results： Bioactivity-directed fractionation of the crude extract of RALP led to the isolation and characterization of the effective compound, namely hignamine. It could dose-dependently relax the isolated guinea pig trachea strip precontraction, with acetylcholine with EC50 value of （2.60±0.36）× 10^5 mol/L. Further in vivo studies also displayed that hignamine could protect experimental asthma model induced by histamine in guinea pigs to prolong the latent periods of asthma. Conclusion： Hignamine, as a β2-AR agonist existing in the extract of RALP, is the key compound contributing to the successful relief of the bronchoconstriction.Aim： To screen beta2-adrenergic receptor Lateralis Preparata （RALP） as potential （β2-AR） agonists from Radix Aconiti drug leads for asthma using a sensitive cell-based agonist assay. Methods： The β2-AR gene was stably expressed by Chinese hamster ovary （CHO） cells also stably expressing a cyclic adenosine monophosphate （AMP） response element-linked enhanced green fluorescent protein reporter gene. The cells were used to screen agonists from high-performance liquid chromatographic fractions of an extract of RALE The fraction with the highest activity was selected for further compound isolation and the study of the structure-activity relationship. Its active compound was further identified by chromatography and mass spectrometry. Results： Bioactivity-directed fractionation of the crude extract of RALP led to the isolation and characterization of the effective compound, namely hignamine. It could dose-dependently relax the isolated guinea pig trachea strip precontraction, with acetylcholine with EC50 value of （2.60±0.36）× 10^5 mol/L. Further in vivo studies also displayed that hignamine could protect experimental asthma model induced by histamine in guinea pigs to prolong the latent periods of asthma. Conclusion： Hignamine, as a β2-AR agonist existing in the extract of RALP, is the key compound contributing to the successful relief of the bronchoconstriction.

关 键 词：beta2-adrenergic receptor （β2-AR） agonists ASTHMA herbal medicines Radix Aconiti Lateralis Preparata （RALP） HIGENAMINE 

分 类 号：R28[医药卫生—中药学]