Rutaecarpine and evodiamine selected as β1-AR inhibitor candidates using β1-AR/CMC-offline-UPLC/MS prevent cardiac ischemia-reperfusion injury via energy modulation.

Abstract In the present study, an offline analytical method combining β 1 -adrenergic receptor/cell membrane chromatography (β 1 -AR/CMC) with ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used for direct recognition, separation, and identification of β 1 -AR inhibitors from Evodia rutaecarpa (Juss) Benth, by which rutaecarpine and evodiamine were screened and identified as potential β 1 -AR antagonists and the β 1 -AR inhibition activity of them was confirmed by downregulation of cAMP and PKA in vitro test. In addition, the results of in vivo pharmacological trials revealed that rutaecarpine (1.1 mg/ml) and evodiamine (1.1 mg/ml) attenuated myocardial infarct size injured by myocardial ischemia/reperfusion, improved metabolism disorders between fatty acid and glucose, increased the content of ATP, Ca 2+ -ATPase activity and reduced the content of peroxisome proliferator-activated receptor α (PPARα) protein level. Thus, the β 1 -AR/CMC-offline-UPLC/MS method developed in this study could be used as an effective alternative for screening β 1 -AR binding bioactive components in traditional Chinese medicines and the bioactive components could be used to remedy cardiac diseases via energy modulation.