Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction

Abstract

Context

Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear.

Objective

We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles.

Materials and methods

Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days’ administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed.

Results

0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%).

Discussion and conclusion

The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Keywords:

• Traditional Chinese medicine (TCM)
• muribaculaceae
• Allobaculum
• Lactobacillus
• serum metabolic biomarker
• 2-n-tetrahydrothiophenecarboxylic acid (THTC)
• lysophosphatidylcholine (lysoPC)

Authors’ contributions

Prof. XY. Wang: Conceptualization, Project administration. XQ. Zhong: Data curation, Writing- original draft. JY. Yan, X. Wei, T. Xie, and ZJ. Zhang: Methodology. KY. Wang, CY. Sun, W. Chen, and JM. Zhu: Visualization, Software. X. Zhao: Writing-review & editing. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data generated for 16S rRNA gene profiling of bacteria are available in the NCBI repository with project accession number PRJNA900688.

Additional information

Funding

This work was supported by National Key R&D Program of China (2022YFC3500300; 2022YFC3500305; 2018YFC1704500); The Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202009).