Protective effects of Shexiang-Tongxin dropping pill against acute myocardial infarction in rats through inhibition of apoptosis and ERK/MAPK signaling pathways

Jun Yan; Hanbing Liu; Jiaxin Shang; Qianqian Fang; Jianfeng Ye; Xiaoyan Lu; Xiaohui Fan

doi:10.1016/j.heliyon.2024.e39939

Protective effects of Shexiang-Tongxin dropping pill against acute myocardial infarction in rats through inhibition of apoptosis and ERK/MAPK signaling pathways

Heliyon. 2024 Oct 29;10(21):e39939. doi: 10.1016/j.heliyon.2024.e39939. eCollection 2024 Nov 15.

Authors

Jun Yan^{1

2}, Hanbing Liu^{1

2}, Jiaxin Shang², Qianqian Fang³, Jianfeng Ye³, Xiaoyan Lu^{2

4

5}, Xiaohui Fan^{1

2

4

5}

Affiliations

¹ State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
² Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
³ Inner Mongolia Conba Pharmaceutical Co., Ltd., Ordos, 017000, China.
⁴ State Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, 314100, Jiaxing, China.
⁵ Jinhua Institute of Zhejiang University, Jinhua, 321299, China.

Abstract

Acute myocardial infarction (AMI) remains a significant health challenge globally, highlighting the ongoing need for effective treatments. Shexiang-Tongxin dropping pill (STDP) is widely utilized as a therapeutic option for AMI in China and Southeast Asia. However, the intricate mechanisms of action of STDP against AMI remain largely unknown. The pharmacodynamic effects of STDP in treating AMI were evaluated both in vitro and in vivo using human umbilical vein endothelial cell oxygen-glucose deprivation, RAW264.7 cell inflammatory injury, and rat left anterior descending surgery models. The whole transcriptome sequencing was performed to analyze gene expression changes in experimental rat hearts after left anterior descending surgery. An integrative approach combining network pharmacology and sequencing data was used to determine the multi-target and multi-pathway mechanisms underlying the action of STDP against AMI. Molecular docking was conducted to identify the primary anti-AMI ingredients in STDP. STDP treatment significantly resisted AMI in vivo and protected against inflammatory and hypoxic injuries in vitro. It resulted in 63 % (901 of 1430) of genes showing restorative regulation in the AMI disease network, relating to the TGF-β, PI3K, apoptosis, and MAPK pathways. Validation experiments indicated that inhibiting apoptosis and ERK/MAPK pathways by reducing Bax and p-ERK1/2 expression levels in rat hearts may be a crucial mechanism of STDP against AMI. Molecular target prediction indicated that tanshinone IIA, salvianolic acid A, salvianolic acid B, and resibufogenin were the essential pharmacodynamic substances of STDP in AMI treatment. This study sheds light on novel mechanisms by which STDP rebalances the AMI disease network through its multi-target and multi-pathway effects. The findings offer data support for the more precise clinical application of STDP.

Keywords: Acute myocardial infarction; Apoptosis signaling pathway; ERK/MAPK signaling pathway; Network pharmacology; Shexiang-tongxin dropping pill.