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

In the present study, an offline analytical method combining β1-adrenergic receptor/cell membrane chromatography (β1-AR/CMC) with ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) was used for direct recognition, separation, and identification of β1-AR inhibitors from Evodia rutaecarpa (Juss) Benth, by which rutaecarpine and evodiamine were screened and identified as potential β1-AR antagonists and the β1-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 (1.1mg/ml) and evodiamine (1.1mg/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 β1-AR/CMC-offline-UPLC/MS method developed in this study could be used as an effective alternative for screening β1-AR binding bioactive components in traditional Chinese medicines and the bioactive components could be used to remedy cardiac diseases via energy modulation.