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.
College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.
Hui
H
Xue
Shanxi Pharmaceutical Vocational College, Taiyuan 030031, China.
Yongjie
Y
Cheng
College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.
Xin
X
Wang
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Yuan
Y
Yue
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Weifang
W
Zhang
College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China. Electronic address: ninili1235@sina.cn.
Xiaoni
X
Li
D058671:Adrenergic beta-1 Receptor Antagonists / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003412:Cricetulus; D004734:Energy Metabolism / Q000187:drug effects*; D032086:Evodia / Q000737:chemistry; D026121:Indole Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D011799:Quinazolines / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D052999:Quinazolinones
D058671:Adrenergic beta-1 Receptor Antagonists; D026121:Indole Alkaloids; D011799:Quinazolines; D018342:Receptors, Adrenergic, beta-1; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine
Cell membrane chromatography; Energy metabolism; Evodiamine; Ischemia/reperfusion; Rutaecarpine; β(1)-Adrenergic receptor