Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression.
Guanxin Shutong capsule is a traditional Chinese medicine for the treatment of myocardial ischemia (MI). Previous studies have shown that the formula has four main active ingredients (FMAI), protocatechuic acid, cryptotanshinone, borneol, and eugenol. However, the mechanisms of action of these FMAI against MI injury are still not well known. The aim of the present study was to evaluate the protective effects of the FMAI on MI in vitro and in vivo. In vitro, rat neonatal cardiomyocytes were isolated, the cell viability and apoptosis rate were, respectively, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and fluorescence activating cell sorter, and the intracellular calcium concentration ([Ca2+]i) and CaM and CaMKII δ mRNA as well as protein levels were determined. Meanwhile, their downstream targets of RyR2 and PLB were also measured by western blot. In vivo, a rat model of coronary artery ligation was used to evaluate the cardioprotective effects. Infarct sizes of heart tissues and levels of serum biochemical indicators, including creatine kinase, lactate dehydrogenase, superoxide dismutase, and glutamate oxaloacetic transaminase, were measured. The in vitro results showed that the FMAI inhibited cell apoptosis, reduced [Ca2+]i, decreased the expression of CaM and CaMKII δ, and increased the expression of RyR2 and PLB. In vivo, the FMAI diminished infract size, reduced creatine kinase, lactate dehydrogenase, and aspartate aminotransferase levels, and enhanced superoxide dismutase activity. In conclusion, our data suggest that the FMAI suppressed calcium overload and exerted its protective effect via its antioxidant, antiinflammatory, and anti-apoptosis activities. Copyright © 2017 John Wiley & Sons, Ltd.
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, PR China.|Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.|Shaanxi Institute of International Trade and Commerce, Xianyang, 712046, PR China.
Feng
F
Liu
Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.|Shaanxi Institute of International Trade and Commerce, Xianyang, 712046, PR China.
Zhuang-Zhuang
ZZ
Huang
Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.
Yu-Hong
YH
Sun
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Ting
T
Li
Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.
Dong-Hua
DH
Yang
Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.
Gang
G
Xu
Shaanxi Buchang Pharmaceutical Co. Ltd, Xi'an, Shaanxi, 710075, PR China.
Ying-Ying
YY
Su
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, PR China.
Tao
http://orcid.org/0000-0003-1823-7164
T
Zhang
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D001892:Camphanes / Q000737:chemistry / Q000494:pharmacology*; D002214:Capsules; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005054:Eugenol / Q000737:chemistry / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001892:Camphanes; D002214:Capsules; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D062385:Hydroxybenzoates; D010616:Phenanthrenes; C000618354:guanxin shutong; C009091:protocatechuic acid; D005054:Eugenol; C037886:cryptotanshinone; C022871:isoborneol; D002118:Calcium
FMAI; calcium overload; myocardial ischemia; protective mechanisms