Buddleoside-Rich Chrysanthemum indicum L. Extract has a Beneficial Effect on Metabolic Hypertensive Rats by Inhibiting the Enteric-Origin LPS/TLR4 Pathway.

Ya-Jun Wang,Wen-Yan Wu,Jie Su,Rong-Shuang Xia,Si-Fan Li,Su-Hong Chen,Qi-Di Huang,Mei-Qiu Yan,Jing-Jing Yu,Gui-Yuan Lv,Bo Li,Meng-Lin Shi

doi:10.3389/fphar.2021.755140

Abstract

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from Chrysanthemum indicum L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

Highlights

Hypertension is one of the common cardiovascular diseases
We demonstrated that buddleoside-rich Chrysanthemum indicum L. extract (BUDE) can improve blood pressure and other markers of metabolic hypertension (MH) in a rat model, and we found that underlying mechanism of action may be related to the regulation of vascular endothelial function by the enteric-origin LPS/Toll-like receptor 4 (TLR4) pathway
After 12 weeks of administration, BUDE-H and BUDE-L could significantly decrease aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and LDL-C levels in serum of model rats (p < 0.01, 0.05), while TG and HDL-C levels showed a trend of improvement, but there was no significant difference

Summary

Introduction

Hypertension is one of the common cardiovascular diseases. According to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Hypertension Guidelines, hypertension is redefined as continuous systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg (Wang Z. et al, 2018). Applying this standard, the prevalence of hypertension would increase from 32 to 45% in the United States and from 23.2 to 46.4% in China (Mills et al, 2020). Metabolic disorders are especially common, occurring in approximately 71.8% of patients with hypertension. Only 10–20% of patients with simple hypertension have no symptoms other than hypertension (Zhu et al, 2013)

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