Abstract

To examine how Jiang-Zhi-Ning (JZN) regulates cholesterol metabolism and compare the role of its four main components. We established a beagle model of hyperlipidemia, fed with JZN extract and collected JZN-containing serum 0, 1, 2, 4, and 6 h later. Human liver cells Bel-7402 were stimulated with 10% JZN-containing serum as well as the four main components of JZN and Atorvastatin. The mRNA expression of LDL receptor (LDL-R), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR), cytochrome P450 7A1 (CYP7A1), and acetyl-Coenzyme A acetyltransferase 2 (ACAT2) was measured by real-time PCR. LDL-R surface expression and LDL-binding and internalization were examined by flow cytometry. The results showed that JZN-containing serum significantly increased the mRNA expression of LDL-R, HMG-CoAR, and CYP7A1 in Bel-7402 cells. All the four components significantly increased the mRNA and protein expression of LDL-R and HMG-CoAR and decreased the mRNA and protein expression of ACAT2 in Bel-7402 cells. Hyperinand chrysophanol also markedly increased the mRNA expression of CYP7A1. Stimulation with stilbene glycosidesignificantly increased the surface expression of LDL-R and the binding and internalization of LDL. In conclusion, JZN and its four components have close relationship with the process of cholesterol metabolism, emphasizing their promising application as new drug candidates in the treatment of hyperlipidemia.

Highlights

  • Numerous studies have shown that cholesterol plays a key role in the development of atherosclerosis, which is the main pathological basis of cardiovascular diseases [1]

  • In Bel-7402 cells, 10% of JZN-containing serum from these beagles significantly increased the mRNA expression of low-density lipoprotein (LDL) receptor (LDL-R), HMG-CoAR, and cytochrome P450 7A1 (CYP7A1) after X h stimulation (P < 0.05, Table 1)

  • The maximum effect was induced by 1-h JZN-containing serum for LDL-R and HMG-CoAR and by 2-h JZN-containing serum for CYP7A1 (Table 1)

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Summary

Introduction

Numerous studies have shown that cholesterol plays a key role in the development of atherosclerosis, which is the main pathological basis of cardiovascular diseases [1]. Multiple clinical experiments have shown that lowering the level of serum total cholesterol, especially LDL cholesterol, can decrease lipid content in atherosclerotic plaques, lessen the shear force from blood on the cap of fibrous tissues, and reduce the secretion of proteases from foam cells that can hydrolyze extracellular matrix This progress can stabilize plaques or even reduce their size, stop disease progression, and decrease cardiovascular morbidity and mortality [2]. LDL-R binds to these lipoproteins and internalizes them into cells, providing lipids for cell proliferation and synthesis of steroid hormones and bile salt These animals metabolized 7.1 pools of LDL-cholesterol (LDL-C) per day, and 79% of this degradation took place in the liver. A functional deficit in LDLR is one of the major causes of hypercholesterolemia and atherosclerosis [4, 5]

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