Suxiao Jiuxin Pill attenuates acute myocardial ischemia via regulation of coronary artery tone

Sa Li; Jiaguo Zhan; Yucheng Wang; Patrick Kwabena Oduro; Felix Boahen Owusu; Jiale Zhang; Ling Leng; Ruiqiao Li; Shujie Wei; Jun He; Qilong Wang

doi:10.3389/fphar.2023.1104243

Suxiao Jiuxin Pill attenuates acute myocardial ischemia via regulation of coronary artery tone

Front Pharmacol. 2023 May 10:14:1104243. doi: 10.3389/fphar.2023.1104243. eCollection 2023.

Authors

Sa Li¹, Jiaguo Zhan¹, Yucheng Wang¹, Patrick Kwabena Oduro¹, Felix Boahen Owusu¹, Jiale Zhang¹, Ling Leng^{1

2}, Ruiqiao Li^{1

2}, Shujie Wei¹, Jun He^{1

2}, Qilong Wang^{1

2

3

4}

Affiliations

¹ Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² State Key Laboratory of Component-Based Chinese Medicine, Ministry of Education, Tianjin, China.
³ Haihe Laboratory of Modern Chinese Medicine, Tianjin, China.
⁴ Endocrinology Department, Fourth Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract

Suxiao Jiuxin Pill (SJP) is a well-known traditional Chinese medicine drug used to manage heart diseases. This study aimed at determining the pharmacological effects of SJP in acute myocardial infarction (AMI), and the molecular pathways its active compounds target to induce coronary artery vasorelaxation. Using the AMI rat model, SJP improved cardiac function and elevated ST segment. LC-MS and GC-MS detected twenty-eight non-volatile compounds and eleven volatile compounds in sera from SJP-treated rats. Network pharmacology analysis revealed eNOS and PTGS2 as the key drug targets. Indeed, SJP induced coronary artery relaxation via activation of the eNOS-NO pathway. Several of SJP's main compounds, like senkyunolide A, scopoletin, and borneol, caused concentration-dependent coronary artery relaxation. Senkyunolide A and scopoletin increased eNOS and Akt phosphorylation in human umbilical vein endothelial cells (HUVECs). Molecular docking and surface plasmon resonance (SPR) revealed an interaction between senkynolide A/scopoletin and Akt. Vasodilation caused by senkyunolide A and scopoletin was inhibited by uprosertib (Akt inhibitor) and eNOS/sGC/PKG axis inhibitors. This suggests that senkyunolide A and scopoletin relax coronary arteries through the Akt-eNOS-NO pathway. In addition, borneol induced endothelium-independent vasorelaxation of the coronary artery. The K_v channel inhibitor 4-AP, K_Ca2+ inhibitor TEA, and K_ir inhibitor BaCl₂ significantly inhibited the vasorelaxant effect of borneol in the coronary artery. In conclusion, the results show that Suxiao Jiuxin Pill protects the heart against acute myocardial infarction.

Keywords: Suxiao Jiuxin Pill; acute myocardial infarction; borneol; scopoletin; senkyunolide a; vasorelaxation.

Grants and funding

This study was supported by the National Key R&D Program of China (2022YFC3501800), The National Program for NSFC, China (81973624), the Science and Technology Program of Tianjin, China (21ZYJDJC00070), and the Innovation Team and Talents Cultivation Program of National Administration of the Traditional Chinese Medicine (ZYYCXTD-D-202002, ZYYCXTD-C-202203).