Microbiome-metabolome reveals that the Suxiao Jiuxin pill attenuates acute myocardial infarction associated with fatty acid metabolism

Jingyu Liao; Yuhao Zhang; Chi Ma; Gaosong Wu; Weidong Zhang

doi:10.1016/j.jep.2023.116529

Microbiome-metabolome reveals that the Suxiao Jiuxin pill attenuates acute myocardial infarction associated with fatty acid metabolism

J Ethnopharmacol. 2023 Aug 10:312:116529. doi: 10.1016/j.jep.2023.116529. Epub 2023 Apr 20.

Authors

Jingyu Liao¹, Yuhao Zhang², Chi Ma³, Gaosong Wu⁴, Weidong Zhang⁵

Affiliations

¹ School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, 510006, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
² School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
³ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: gaosong@shutcm.edu.cn.
⁵ School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, 510006, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; School of Pharmacy, Second Military Medical University, Shanghai, 200433, China. Electronic address: wdzhangy@hotmail.com.

PMID: 37086873
DOI: 10.1016/j.jep.2023.116529

Abstract

Ethnopharmacological relevance: The Suxiao Jiuxin pill (SJP) is a Chinese medical patent drug on the national essential drug list of China, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been elucidated clearly, especially its relationship with the gut microbiota.

Aim of the study: This study aimed to investigate the cardioprotective effect of SJP against isoproterenol-induced acute myocardial infarction (AMI) by integrating the gut microbiome and metabolome.

Methods: A rat model of AMI was generated using isoproterenol. Firstly, the effect of antibiotic (ABX) treatment on the blood absorption and excretion of the main components of SJP were studied. Secondly, 16S rRNA sequencing and untargeted metabolomics were used to discover the improvement of SJP treatment on gut microbiota and host metabolism in AMI rats. Finally, targeted metabolomics was used to verify the effects of SJP treatment on host metabolism in AMI rats.

Result: The results showed that ABX treatment could affect the blood absorption and fecal excretion of the main active components of SJP. At the same time, SJP can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Jeotgalicoccus, Lachnospiraceae, and Blautia) are significantly associated with fatty acids. Untargeted metabolomics also found that SJP could restore the levels of various fatty acid metabolites in serum and cecal contents (p < 0.01, FC > 1.5 and VIP >1). Targeted metabolomics further confirmed that 41, 21, and 39 fatty acids were significantly altered in serum, cecal contents, and heart samples, respectively. Interestingly, these fatty acids belong to the class of eicosanoids, and SJP can significantly downregulate these eicosanoids in AMI rats.

Conclusion: The results of this study suggest that SJP may exert its cardioprotective effects by remodeling the gut microbiota and host fatty acid metabolism.

Keywords: Acute myocardial infarction; Gut microbiota; Metabolome; Suxiao Jiuxin pill; Traditional Chinese medicine.

MeSH terms

Animals
Drugs, Chinese Herbal* / pharmacology
Drugs, Chinese Herbal* / therapeutic use
Fatty Acids
Isoproterenol
Metabolome
Metabolomics / methods
Microbiota*
Myocardial Infarction* / drug therapy
RNA, Ribosomal, 16S / genetics
Rats

Substances

Isoproterenol
RNA, Ribosomal, 16S
Drugs, Chinese Herbal
Fatty Acids