The Different Therapeutic Effects of Traditional Chinese Medicine Shensong
Yangxin Capsule and Salubrinal in High-intensity Exercise-induced
Heart Failure in Rats with Acute Myocardial Infarction
Authors: Lu Junli , Ma Yanzhuo , Lv Hongzhi , Li Congxin , Ru Leisheng , Zhao Jian , Wang Dongmei 
Published: February 2024

Background:
Currently, endoplasmic reticulum stress is studied utilizing a
dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation
Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia.
However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart
failure in myocardial tissue have not yet been investigated.

Objective:
The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule
(SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced
by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated.

Methods:
Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of
four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group
(AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by
left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to
simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week,
echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left
ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each
group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and
measure the percentage of apoptosis in each group; Western blotting was applied to detect the
cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to
detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum.

Results:
Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group
were statistically significantly reduced, while LVESV were significantly higher, compared to
those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly
better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo
group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the
AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell
infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the
AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than
that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately
21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the
AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared
to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably
reduced in the AMI+Shensong group and AMI+Sal group， compared to the
AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal
group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly
lower, and MDA was significantly higher in the AMI+placebo group. Compared to the
AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was
significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05)

Conclusion:
In rats with acute myocardial infarction in high-intensity exercise-induced heart
failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction.
SSYX has a shorter course of treatment and a better therapeutic effect than Sal.