Open AccessIdentification of higenamine in Radix Aconiti Lateralis Preparata as a beta2‐adrenergic receptor agonist 1
Author(s) -
BAI Gang,
YANG Yang,
SHI Qian,
LIU Ze,
ZHANG Qi,
ZHU Yuanyuan
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00859.x
Subject(s) - chinese hamster ovary cell , chemistry , agonist , histamine , pharmacology , partial agonist , bronchoconstriction , guinea pig , receptor , phosphodiesterase , biochemistry , endocrinology , medicine , enzyme , biology , asthma
Aim: To screen beta2‐adrenergic receptor (β 2 ‐AR) agonists from Radix Aconiti Lateralis Preparata (RALP) as potential drug leads for asthma using a sensitive cell‐based agonist assay. Methods: The β 2 ‐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 RALP. 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 fraction‐ation 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 EC 50 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 β 2 ‐AR agonist existing in the extract of RALP, is the key compound contributing to the successful relief of the bronchoconstriction.