title: Bioactive equivalence of combinatorial components identified in screening of an herbal medicine.
abstract: OBJECTIVE
  To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of constituents.
  
  
  METHODS
  We developed a bioactive equivalence oriented feedback screening method and applied it to discover the BECCs from an herbal preparation Cardiotonic Pill (CP). The operations include chemical profiling of CP, followed by an iterative loop of determining, collecting and evaluating candidate BECCs.
  
  
  RESULTS
  A combination of 18 compounds was identified as BECCs from CP, which accounts for 15.0% (w/w) of original CP. We have demonstrated that the BECCs were as effective as CP in cell models and in a rat model of myocardial infarction.
  
  
  CONCLUSIONS
  This work answers the key question of which are real bioactive components for CP that have been used in clinic for many years, and provides a promising approach for discovering BECCs from herbal medicines. More importantly, the BECCs could be extended to improve quality control of herbal products and inspire an herbal medicines based discovery of combinatorial therapeutics.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Long
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Hao
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Shi
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhang
authors.forename: Hao-Chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Qian-Ying
authors.initials: QY
authors.lastname: Wen
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Xi-Juan
authors.initials: XJ
authors.lastname: Jiang
authors.forename: Bo-Li
authors.initials: BL
authors.lastname: Zhang
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Qi
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D008517:Phytotherapy; D028321:Plant Preparations / Q000737:chemistry* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D004338:Drug Combinations; D028321:Plant Preparations