Protective Mechanisms of Suxiao Jiuxin Pills (速效救心丸) on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro

Abstract

Percutaneous coronary intervention (PCI) is a milestone in treating acute myocardial infarction (AMI). Early reperfusion can instantaneously open the occluded coronary artery, rescuing the ischemic myocardium. (1) However, myocardial ischemia and reperfusion (I/R) injury, which can trigger death of myocytes, seriously affects clinical effectiveness of PCI. An animal study showed that 50% of the infarct area were caused by myocardial I/R injury. (2) Many signaling molecules and mechanisms are postulated to modulate myocardial I/R injury, such as calcium overload, reactive oxygen species, energy metabolism dysfunction of myocardial fibers, cellular adhesion molecules, neutrophils, vascular endothelial cells, and apoptosis, etc. (1) Several agents, such as freeradical scavengers and inhibitors of the immune system, have been shown to protect heart from I/R injury. Although it has been actively studied for more than 35 years, myocardial I/R injury is still not yet treated effectively. The high mortality and non-availability of suitable drug treatments led to heightened interest in developing early stage therapies to prevent death of myocytes following myocardial I/R, and to improve the life span and quality in patients after AMI. (3) Suxiao Jiuxin Pill (速效救心丸, SXJ), which formula can be found in the latest 2015 Chinese Pharmacopoeia, is made up of 2 herbs, Rhizoma Chuanxiong and Borneolum. (4) SXJ contains 4 active ingredients: ferulic acid, menthol, borenol, and isoborneol; and is widely used for treating AMI and angina pectoris in China for more than 30 years. (5) Previous publications reported that SXJ could alleviate acute myocardial ischemia, prevent the formation of atherosclerosis (AS) and induce potent relaxation and inhibition on contraction in human artery.

Suxiao Jiuxin Pill alleviates myocardial ischemia–reperfusion injury through the ALKBH5/GSK3β/mTOR pathway

“…2c, d, the level of p-GSK3β/GSK3β was significantly upregulated while p-mTOR/mTOR was downregulated when rats were exposed to the I/R condition and SJP groups altered the expression of these two proteins compared to the I/R group. In the current study, the effect of SJP on GSK3β expression in MIRI rats was consistent with the results of Tan et al [15]. Furthermore, our results revealed that SJP inhibits autophagy through GSK3β/mTOR pathway in MIRI rats.…”

“…Our previous clinical study confirmed that SJP alleviates major adverse cardiovascular events and improves heart function in acute coronary syndrome (ACS) patients with early revascularization [14], suggesting SJP may mitigate MIRI [15]. Despite its extensive clinical use in China, only few studies have reported the detailed effects of SJP on MIRI [15], and the underlying mechanisms of these effects are undefined.…”

“…Pharmacological studies have shown that SJP has multiple effects, including dilating coronary arteries, dilating vascular smooth muscle, reducing myocardial ischemia, protecting cardiomyocytes, inhibiting the formation of atherosclerotic plaques, reducing blood viscosity and significantly relieving spasm and analgesia [13]. Our previous clinical study confirmed that SJP alleviates major adverse cardiovascular events and improves heart function in acute coronary syndrome (ACS) patients with early revascularization [14], suggesting SJP may mitigate MIRI [15]. Despite its extensive clinical use in China, only few studies have reported the detailed effects of SJP on MIRI [15], and the underlying mechanisms of these effects are undefined.…”