Abstract

Taoren Honghua drug is a traditional Chinese medicinal drug used to treat cardiovascular disease. The aim of the study is to investigate the effects of Taoren Honghua drug on inflammation and atherosclerosis in ApoE knock-out mice and RAW264.7 cells. ApoE knock-out mice fed with high fat diet for 8 weeks were randomly divided into five groups and then continued the high fat diet, or plus Taoren Honghua drug at concentrations of 3.63, 1.815, and 0.9075 g/ml, or plus Simvastatin at 2.57 mg/kg. RAW 264.7 cells were intervened with lipopolysaccharide or lipopolysaccharide plus different concentrations of Taoren Honghua drug. Compared to mice only with high fat diet, mice with high fat diet and Taoren Honghua drug showed lower body weight, triglyceride, cholesterol, IL-6 and TNF-α, smaller plaque sizes, less lymph vessel, and T cell contents of lymph nodes, but higher IL-10 level. In RAW264.7 cells, groups with LPS plus Taoren Honghua drug had lower IL-6 and TNF-α, but higher IL-10 than LPS group, as revealed by PCR or ELISA methods. A decrease of total or phosphorylated ERK1/2, JNK, p38, ERK5, STAT3, and AKT were detected, so was the translocation of NF-κB p65 from nuclear to cytoplasm. These results suggested that Taoren Honghua drug could attenuate atherosclerosis and play an anti-inflammatory role via MAPKs, ERK5/STAT3, and AKT/NF-κB p65 signaling pathways in ApoE knock-out mice and lipopolysaccharide-induced RAW264.7 cells.

Highlights

  • Cardiovascular disease (CVD) is the second leading cause of death in the overall population (Barish et al, 2019) with a prevalence of 48.0% in adults according to the data from 2013 to 2016 (Benjamin et al, 2019)

  • Chronic inflammation worsens the condition by increasing cytokines (Patil et al, 2019)

  • As coronary artery disease (CAD) or AS is associated with inflammation, anti-inflammation is an effective therapeutic strategy to prevent disease progression (Gaudino and Crea, 2019)

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Summary

Introduction

Cardiovascular disease (CVD) is the second leading cause of death in the overall population (Barish et al, 2019) with a prevalence of 48.0% in adults (older than 20 years) according to the data from 2013 to 2016 (Benjamin et al, 2019). Atherosclerosis (AS) is a pathological manifestation in most CVD patients (Conte and Vale, 2018). Inflammatory response runs through the whole AS process (Christodoulidis et al, 2014; Momiyama et al, 2014) and increases the rate of cardiovascular death. A clinical trial has verified anti-inflammatory interventions are more precise and personalized for patients with CAD (Libby, 2017). The AS guidelines and clinical treatment schemes still aim to lower blood lipids and stabilize plaques (Khan et al, 2015). No targeted treatment for acute and chronic inflammation has been widely applied

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