Drug Design, Development and Therapy (Feb 2023)
Efficacy and Mechanism of Qianshan Huoxue Gao in Acute Coronary Syndrome via Regulation of Intestinal Flora and Metabolites
Abstract
Ning Zhao,1,2 Yan Ma,3 Xiaoxue Liang,2 Yu Zhang,4 Dacheng Hong,5 Ying Wang,2 Dong Bai2 1Department of Pharmacy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Formula-Syndrome Research Center, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 3Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria; 4Beijing Xiuzheng Pharmaceutical Company, Beijing, People’s Republic of China; 5Department of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaCorrespondence: Dong Bai, Tel +86 13552343081, Fax +8610 64089002, Email [email protected]: 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: traditional Chinese medicine, acute coronary syndrome, 16S rRNA, ethanolamine, topical paste
