Cardioprotective Effect of Danshensu against Ischemic/Reperfusion Injury via c‐Subunit of ATP Synthase Inhibition

Abstract

Mitochondrial permeability transition pore (MPTP) opening is the main culprit of ischemic/reperfusion (IR) injury. It is reported that c-subunit of ATP synthase is the core component of MPTP. Danshensu (DSS), a monomer isolated from the traditional Chinese herb Danshen, has showed cardioprotective effect against IR injury through unknown mechanism. In this study, rat hearts were suspended in Langendorff instrument and perfused with Krebs-Henseleit (KH) buffer containing DSS for 60 minutes, followed by 30 minutes of global ischemia. Parameters including heart rate, left ventricular developed pressure, and the rate of left ventricle diastolic pressure change were recorded to assess their cardiac function. All these indexes were improved in DSS group. The rate of cardiomyocytes apoptosis and MPTP opening were both inhibited in DSS group. In addition, DSS administration leads to downregulation of c-subunit of ATP synthase in both mRNA and protein levels. Consistently, when c-subunit of ATP synthase was overexpressed in H9C2 cells through pcDNA3/5G1 plasmid transfection, MPTP opening was enhanced when the cardioprotective effect of DSS also tapers. In conclusion, DSS could alleviate cardiac IR injury via inhibiting c-subunit of ATP synthase expression.

Danshensu for Myocardial Ischemic Injury: Preclinical Evidence and Novel Methodology of Quality Assessment Tool

“…Then secondary screening was conducted by reading the full text of the remaining 46 studies, and 19 studies were excluded because of at least one of the following reasons: (1) failed to obtain full text; (2) not DSS intervention; (3) inappropriate animal model; (4) combined use of other drugs in treatment group; (5) compared with herbs or active herbal compounds; (6) no control group; (7) master dissertation or doctoral dissertation; (8) no available data. Ultimately, 27 eligible studies (Jiang et al, 1982; Tang et al, 1989, 2018; Li et al, 1996, 2012, 2016; Dong et al, 2009; Xiang et al, 2009; Cheng et al, 2010; Lu et al, 2010; Zhang et al, 2010; Quan et al, 2012; Zhao et al, 2012; Cui G. et al, 2013; Yin et al, 2013, 2017; Chen et al, 2014; Cui et al, 2014; Yu J. et al, 2015; Fan et al, 2016; Hu et al, 2016; Song et al, 2016; Wang et al, 2016, 2017; Wei et al, 2016; Gao et al, 2017; Zhang X. et al, 2017) were selected (Figure 1A).…”

“…Eleven studies were published in chinese (Jiang et al, 1982; Tang et al, 1989; Li et al, 1996; Xiang et al, 2009; Cheng et al, 2010; Lu et al, 2010; Zhang et al, 2010; Quan et al, 2012; Zhao et al, 2012; Chen et al, 2014; Wei et al, 2016), and the rest was published in English (Dong et al, 2009; Li et al, 2012, 2016; Cui G. et al, 2013; Yin et al, 2013, 2017; Yu J. et al, 2015; Fan et al, 2016; Hu et al, 2016; Song et al, 2016; Wang et al, 2016, 2017; Gao et al, 2017; Zhang X. et al, 2017; Tang et al, 2018) between 1982 and 2018. Sprague-Dawley (SD) male rats were used in 21 studies (Dong et al, 2009; Xiang et al, 2009; Lu et al, 2010; Zhang et al, 2010; Li et al, 2012, 2016; Quan et al, 2012; Zhao et al, 2012; Cui G. et al, 2013; Yin et al, 2013, 2017; Chen et al, 2014; Cui et al, 2014; Yu J. et al, 2015; Fan et al, 2016; Hu et al, 2016; Song et al, 2016; Wei et al, 2016; Gao et al, 2017; Wang et al, 2017; Zhang X. et al, 2017), two that used male Wistar rats (Tang et al, 1989; Li et al, 1996), one that used both female and male Wistar rats (Cheng et al, 2010), two that used Zebrafish embryos (Wang et al, 2016; Tang et al, 2018) and one that used male canines with unknow species (Jiang et al, 1982). The weight of the rats were 180–320 g, and the canines were 12–26 kg.…”

“…To induce anesthesia, 16 studies used nembutal (Jiang et al, 1982; Tang et al, 1989; Li et al, 1996, 2012, 2016; Xiang et al, 2009; Cheng et al, 2010; Quan et al, 2012; Yin et al, 2013, 2017; Chen et al, 2014; Yu J. et al, 2015; Fan et al, 2016; Hu et al, 2016; Wang et al, 2017; Zhang X. et al, 2017) seven studies used chloral hydrate (Dong et al, 2009; Zhang et al, 2010; Zhao et al, 2012; Cui G. et al, 2013; Cui et al, 2014; Wei et al, 2016; Gao et al, 2017); and two studies used ethyl carbamate (Lu et al, 2010; Song et al, 2016). Fifteen MI models were produced by ligation of the left anterior descending coronary artery (LAD) (Jiang et al, 1982; Dong et al, 2009; Xiang et al, 2009; Lu et al, 2010; Quan et al, 2012; Zhao et al, 2012; Cui G. et al, 2013; Yin et al, 2013, 2017; Chen et al, 2014; Cui et al, 2014; Hu et al, 2016; Wei et al, 2016; Wang et al, 2017; Zhang X. et al, 2017) seven models produced by the langendorff method (Tang et al, 1989; Li et al, 1996; Cheng et al, 2010; Zhang et al, 2010; Yu J. et al, 2015; Fan et al, 2016; Gao et al, 2017); three models produced by subcutaneous injection of Isoproterenol (ISO) (Li et al, 2012, 2016; Song et al, 2016); and the remain two by exposure to Doxorubicin (Dox) (Wang et al, 2016; Tang et al, 2018). For outcome measures, 16 studies reported the MI size (Jiang et al, 1982; Dong et al, 2009; Xiang et al, 2009; Lu et al, 2010; Li et al, 2012; Quan et al, 2012; Cui G. et al, 2013; Yin et al, 2013, 2017; Chen et al, 2014; Cui et al, 2014; Yu J. et al, 2015; Hu et al, 2016; Wei et al, 2016; Wang et al, 2017; Zhang X. et al, …”

“…Five studies were published in chinese (Zhu et al, 1999; Guo et al, 2006; Zhao et al, 2012; Cui Q. B. et al, 2013; Xu et al, 2013), and the rest was published in English (Dong et al, 2009; Cui G. et al, 2013; Yin et al, 2013; Fan et al, 2016; Hu et al, 2016; Meng et al, 2016; Wang et al, 2016, 2017; Gao et al, 2017; Zhang X. et al, 2017; Tang et al, 2018) between 1999 and 2017. H9c2 cells (Zhao et al, 2012; Cui G. et al, 2013; Cui Q.…”

Modulatory Effects of Chinese Herbal Medicines on Energy Metabolism in Ischemic Heart Diseases

“…Salvia miltiorrhiza Bunge (also called Danshen), another blood-replenishing and stasis-resolving TCM herb, has shown therapeutic promise for multiple cardiovascular diseases. Salvianic acid A (Danshensu) is one of the major water-soluble compounds derived from Salvia miltiorrhiza and has been reported to alleviate cardiac I/R injury by inhibiting mPTP opening and expression of the ATP synthase c-subunit ( Gao et al., 2017 ). 3, 4-Dihydroxylphenyl lactic acid (DLA) is another name for Salvianic acid A, which has been demonstrated to reduce infarction size and enhance mitochondrial aerobic respiration in myocardial I/R injury.…”