Efficacy and Mechanism of Qianshan Huoxue Gao in Acute Coronary Syndrome via Regulation of Intestinal Flora and Metabolites

Drug Des Devel Ther. 2023 Feb 22:17:579-595. doi: 10.2147/DDDT.S396649. eCollection 2023.

Abstract

Purpose: To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation.

Methods: Male Sprague-Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics.

Results: Compared with controls, CK-MB and cTnI were increased (P<0.01); ejection factor and fractional shortening were decreased (P<0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased (P<0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which Bacteroides, Lactobacillus, and Rikenellaceae_RC9_gut_group are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with Eubacterium xylanophilum group, Ruminococcus, unclassified f__Oscillospiraceae, Intestinimonas, Eubacterium siraeum group, Lachnospiraceae NK4A136 group, and norank f__Desulfovibrionaceae.

Conclusion: QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.

Keywords: 16S rRNA; acute coronary syndrome; ethanolamine; topical paste; traditional Chinese medicine.

MeSH terms

  • Acute Coronary Syndrome*
  • Animals
  • Atorvastatin
  • C-Reactive Protein
  • Ethanolamine
  • Ethanolamines
  • Gastrointestinal Microbiome*
  • Interleukin-2
  • Interleukin-6
  • Male
  • RNA, Ribosomal, 16S
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-2
  • Atorvastatin
  • C-Reactive Protein
  • Interleukin-6
  • RNA, Ribosomal, 16S
  • Ethanolamine
  • Ethanolamines

Grants and funding

This research was funded by State Drug Administration “Science and technology help the economy 2020” key special projects and China Academy of Chinese Medical Independent Selection (YZ-1782) and also supported by the Chinese Government Scholarship (No. 202005350010).