title: Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization.
abstract: OBJECTIVE
  We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME).
  
  
  METHODS
  SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses.
  
  
  RESULTS
  Pretreatment with the combination of ligustrazine (27 mg·kg(-1)·d(-1)) and berberine (90 mg·kg(-1)·d(-1)) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg(-1)·d(-1)).
  
  
  CONCLUSIONS
  The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.
authors.affiliation: Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.|China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Xiao-juan
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Chun-yu
authors.initials: CY
authors.lastname: Guo
authors.affiliation: China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Ming-ming
authors.initials: MM
authors.lastname: Wang
authors.affiliation: Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.|China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Na
authors.initials: N
authors.lastname: Kou
authors.affiliation: Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.|China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Qu
authors.affiliation: Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.|China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Mao
authors.affiliation: China Heart Institute of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Cardiovascular Diseases Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
authors.forename: Da-zhuo
authors.initials: DZ
authors.lastname: Shi
mesh_terms: D000818:Animals; D001599:Berberine / Q000627:therapeutic use*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D004617:Embolism / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
chemical_list: D011719:Pyrazines; D001599:Berberine; C017953:tetramethylpyrazine