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

Aim: To screen beta2-adrenergic receptor (β₂-AR) agonists from Radix Aconiti Lateralis Preparata (RALP) as potential 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 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 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. [ABSTRACT FROM AUTHOR]