Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effect of Shexiang Baoxin Pill on Inhibiting Atherosclerosis in ApoE-/- Mice by Reshaping Gut Microbiota and Fecal Metabolites

Version 1 : Received: 7 July 2023 / Approved: 10 July 2023 / Online: 11 July 2023 (10:25:05 CEST)

How to cite: Xie, B.; Zu, X.; Wang, Z.; Xu, X.; Xin, J.; Fu, P.; Liu, R. Effect of Shexiang Baoxin Pill on Inhibiting Atherosclerosis in ApoE-/- Mice by Reshaping Gut Microbiota and Fecal Metabolites. Preprints 2023, 2023070687. https://doi.org/10.20944/preprints202307.0687.v1 Xie, B.; Zu, X.; Wang, Z.; Xu, X.; Xin, J.; Fu, P.; Liu, R. Effect of Shexiang Baoxin Pill on Inhibiting Atherosclerosis in ApoE-/- Mice by Reshaping Gut Microbiota and Fecal Metabolites. Preprints 2023, 2023070687. https://doi.org/10.20944/preprints202307.0687.v1

Abstract

Background: Atherosclerosis (AS), a key pathological contributor of cardiovascular diseases (CVDs), was characterized by formation of atherosclerotic plaque in aortic wall and caused high mortality and morbidity worldwide. Factors contributing to the initiation and progression of AS included vascular endothelial dysfunction, dyslipidemia, inflammation, and oxidative stress. Shexiang Baoxin Pill (SBP) was a traditional Chinese medicine that had been widely applied in clinic and proved to be effective for patients with CVDs. However, the mechanisms underlying its anti-atherosclerotic effects have not been completely elucidated. The study aimed to investigate the protective effects of SBP on AS and its potential mechanisms. Methods: Different dose of SBP was orally administered in apolipoprotein E-deficient (ApoE-/-) mice treated with a high-fat diet (HFD). Histopathological and immunohistochemical analysis, ELISA, untargeted metabolomics analysis, 16S rRNA sequence analysis, and spearman analysis were applied to identify the protective effects and mechanisms of SBP in HFD-induced AS. Results: SBP significantly alleviated HFD-induced atherosclerotic lesion both in aorta and aortic sinus with a reduction in serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased high-density lipoprotein cholesterol (HFD-C) level with no significant change of body weight in HFD-induced ApoE-/- mice. Mechanismly, SBP markedly reshaped the gut microbiota composition and associated metabolomic characteristics. 2 differential intestinal floras at phylum level and 8 differential microbes at genus level, 5 metabolic pathways and 9 differential fecal metabolites related to CVDs were figured out. Besides, intensive correlation between 8 differential microbes and 9 fecal metabolites was observed. Conclusions: Our results showed that SBP could improve HFD-triggered serum lipid disorder, systematic inflammation, and contribute to the alleviation of atherosclerotic lesion. The antiatherogenic properties of SBP might partly result from the reshaping of the gut microbiota and fecal metabolic profile.

Keywords

Shexiang Baoxin Pill; Atherosclerosis; Gut microbiota; Fecal metabolites; Correlation

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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