The Enhanced Pharmacological Effects of Modified Traditional Chinese Medicine in Attenuation of Atherosclerosis Is Driven by Modulation of Gut Microbiota.

Wenyan Ji,Chenchen Ma,Fei Teng,Ting Jiang,Shi Huang,Suhua Yan,Zheng Sun

doi:10.3389/fphar.2020.546589

Abstract

Accumulating evidence indicated that gut microbiota-targeted therapy is a promising strategy to treat Cardiovascular Disease (CVD). Traditional Chinese Medicine (TCM) has been used in CVD treatments for over 2,000 years which is believed to result from the modulation of gut microbiota, yet the underlying mechanism remains elusive. According to the theoretical system of TCM, we developed an innovative formula of TCM named “TongMai ZhuYu (TMZY)” on top of one classic Chinese herbal formula [“XueFu ZhuYu (XFZY)”], which can more effectively alleviate CVD in the clinical practice. Here, we first systematically assessed the pharmacological effects of TMZY, XFZY, and atorvastatin on atherosclerosis (AS) induced by high-fat diet (HFD) in rats. TMZY typically outperformed others in alleviating AS rats by characterization of pathological morphology, immunohistochemistry, inflammatory cytokines. Remarkably, combining this modified TCM formula (TMZY) with atorvastatin can further help the alleviation of AS in rats by suppressing immune and inflammatory responses. Furthermore, to test whether TMZY alleviated AS symptoms by altering gut microbial compositions (dysbiosis), we employed 16S amplicon sequencing to investigate gut microbiota changes in the AS mice induced by high choline diet (HCD) using both TMZY and XFZY under antibiotic-treated and untreated conditions. TCM formulas induced consistent and remarkable changes in the phenotypes and microbiota in the HCD mice. TMZY modulated more changes in the gut microbiota to improve diseased phenotypes than XFZY. Notably, the TMZY-intervention effect on CVD in mice attenuated after the suppression of gut microbial activity by antibiotics. Collectively, we demonstrated that TCM herbals could effectively modulate the gut microbiota as a mechanism for altering the pathogenesis of cardiovascular disorders in mice/rats.

Highlights

Cardiovascular Diseases (CVD) are the number one cause of global death
To systematically assess the pharmacological effects of those treatments, we carefully examined the changes of pathological morphology, immunohistochemistry (IHC), and the levels of inflammatory cytokines
Compared with the healthy control group (Figure 2A), aortic intima thickening, partial loss of endothelial cells, the proliferation of smooth muscle cells (SMCs), and appearance of lipid plaques, foam cell accumulation, and necrotic substances were observed in the high-fat diet (HFD) group (Figure 2B)

Summary

Introduction

Cardiovascular Diseases (CVD) are the number one cause of global death (around 31% annually in 2016). Atherosclerosis (AS) is widely considered as the most common issue for the prevention and treatment of CVD (Benjamin et al, 2018). The typical treatments (such as statins) in Western medicine against AS exhibited a substantial effect on anti-AS and lowering lipid. Clinicians have begun to consider the potential role of Traditional Chinese Medicine (TCM) in the prevention and treatment of CVD because of the unmet needs for CVD control using Western medicine. Multiple basic and clinical studies related to TCM formulas have drawn increasing attention from the cardiovascular community (Hao et al, 2017; Wang et al, 2018). Multiple TCM formulas or Chinese herbal monomers have proven to be active on the regulation of serum lipid metabolism, protection of vascular endothelial cells, anti-coagulation, anti-oxidation, inhibition of inflammation, etc. Multiple TCM formulas or Chinese herbal monomers have proven to be active on the regulation of serum lipid metabolism, protection of vascular endothelial cells, anti-coagulation, anti-oxidation, inhibition of inflammation, etc. (Liu et al, 2012; Liu and Huang, 2016; Zhang et al, 2019)

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