title: Cimicifugamide from Cimicifuga rhizomes functions as a nonselective β-AR agonist for cardiac and sudorific effects.
abstract: Cimicifuga rhizomes (CR) are used in the treatment of respiratory and cardiovascular diseases in traditional Chinese medicine, but their key effective components and mechanism of action have not yet been reported. In this study, the cardiac, antipyretic and sudorific effects of CR were evaluated using the toad heart failure in vitro model and mice fever and sweating in vivo models. Moreover, the UPLC/Q-TOF-MS-integrated β2-AR luciferase reporter gene assay system was used to screen the bioactive ingredients from CR extract, and the activity of this ingredient were verified using the above-mentioned in vitro and vivo models. Our results showed that CR had anti-heart failure, antipyretic and sweating effects, which could be antagonized by propranolol. On the other hand, cimicifugamide was screened as β2-AR agonist from CR and cimicifugamide could activate β1, 2-ARs more significantly than β3-AR in β-ARs selectivity assessment. The results not only revealed the key effective components and mechanism of CR in traditional use but also supplied a characteristic complementary ingredient for quality control of CR.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: yongjiankang1@163.com.
authors.forename: ZengYong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: wontch@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: 940310803@qq.com.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: huxueyan323@foxmail.com.
authors.forename: XueYan
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: guoyuding@mail.nankai.edu.cn.
authors.forename: GuoYu
authors.initials: G
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: minjiang@nankai.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: gangbai@nankai.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D031885:Cimicifuga / Q000737:chemistry*; D003412:Cricetulus; D004195:Disease Models, Animal; D006027:Glycosides / Q000494:pharmacology*; D057809:HEK293 Cells; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D006027:Glycosides; D010936:Plant Extracts; C442157:cimicifugamide; D007545:Isoproterenol
keywords: Antipyretic; Cardiac; Cimicifuga rhizomes; Cimicifugamide; Sudorific; β-AR agonist