Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression

Abstract

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 ([Ca ] ) 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 [Ca ] , 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.

Mechanisms Underlying the Cardioprotection of YangXinDingJi Capsule against Myocardial Ischemia in Rats

“…e cardiac muscle disease has partially been reported, and some authors proved an alteration of calcium homeostasis, especially in L-type voltage-gated calcium channel (VGCC) expression and regulation. TCM as therapy for MI has better prospects because of its components and targets [28].…”

Therapeutic Effects of Traditional Chinese Medicine on Cardiovascular Diseases: the Central Role of Calcium Signaling

“…In addition to regulating LTCCs, which are responsible for the Ca 2+ influx in cardiomyocytes, RyRs that mediate intracellular Ca 2+ release from SR are also valid targets for TCM (Lei et al, 2018). FMAI from Guanxin Shutong capsule increased the expression of RyR2 and PLN in cardiomyocytes (Liu et al, 2017b). As a crucial calcium removal mechanism, NCX, in its forward mode, pumps 1 Ca 2+ out of cells in exchange for 3 Na + to reduce [Ca 2+ ] i (Pott et al, 2011).…”

“…Xin-Ke-Shu (XKS), Guanxinshutong capsule (GXSTC), modified Yiqi decoction (MYQ), and other Chinese herbal compound preparations are involved in the regulation of calcium signaling during the treatment of coronary heart disease and myocardial infarction (Yang et al, 2018a;Liu et al, 2017b;Yu et al, 2017) (Table 5). Xin-Ke-Shu tablet (XKS) is mainly composed of Salvia miltiorrhiza, Radix Puerariae, Hawthorn, Panax Notoginseng and Radix Aucklandiae.…”

The Role of Essential Oils and Their Main Compounds in the Management of Cardiovascular Disease Risk Factors

“…Borneol increased cell viability on hypoxia/reoxygenation-stimulated cardiomyocytes [188]. On an in vitro model of ischemia/reperfusion, eugenol increased cell viability of cardiomyocytes subjected to hypoxia/reoxygenation [188]. Eugenol reduced the acute cardiotoxicity elicited by doxorubicin [189] and on an isoproterenol-induced myocardial infarction model.…”

“…In addition, this compound also inhibited the outgrowth of aortic sprouts as well as neointima formation [187]. Borneol increased cell viability on hypoxia/reoxygenation-stimulated cardiomyocytes [188]. On an in vitro model of ischemia/reperfusion, eugenol increased cell viability of cardiomyocytes subjected to hypoxia/reoxygenation [188].…”