Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9

Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9

Numerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein converta...

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Main Authors: Liping Qu, Didi Li, Xiaoping Gao, Yongwei Li, Jianming Wu, Wenjun Zou
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-11-01
Series:Frontiers in Pharmacology
Subjects:
Di’ao Xinxuekang
LDL-C
PCSK9
LDLR
ApoE–/– mice
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.01170/full
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spelling doaj-784b124bd0ef443aa69e1c018927e0fc2020-11-25T01:42:31ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-11-01910.3389/fphar.2018.01170414709Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9Liping Qu0Didi Li1Xiaoping Gao2Yongwei Li3Jianming Wu4Wenjun Zou5School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of New Drug Research and Development, National Engineering Research Center for Natural Medicines, Chengdu, ChinaLaboratory of Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaNumerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis regulation. The inducement of PCSK9 expression is also an important reason for statin intolerance. The Di’ao Xinxuekang (DXXK) capsule extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product used in atherosclerotic cardiovascular disease. Although DXXK has been widely used in atherosclerotic cardiovascular treatment for nearly 30 years, studies on the potential mechanisms of the lipid-lowering effect are very limited. The purpose of the present study was to demonstrate the possible involvement of the PCSK9/LDLR signaling pathway in the lipid-lowering and antiatherosclerotic effect of DXXK in high-fat diet-fed ApoE–/– mice. The results showed that DXXK treatment alleviated hyperlipidemia, fat accumulation, and atherosclerosis formation in ApoE–/– mice. Furthermore, changes in the expression of PCSK9 mRNA in liver tissue and the circulating PCSK9 level in ApoE–/– mice were both reversed after DXXK treatment, and upregulation of LDLR in the liver was also detected in the protein level in DXXK-treated mice. Our study is the first to show that DXXK could alleviate lipid disorder and ameliorate atherosclerosis with downregulation of the PCSK9 in high-fat diet-fed ApoE–/– mice, suggesting that DXXK may be a potential novel therapeutic treatment and may support statin action in the treatment of atherosclerosis.https://www.frontiersin.org/article/10.3389/fphar.2018.01170/fullDi’ao XinxuekangLDL-CPCSK9LDLRApoE–/– mice
collection DOAJ
language English
format Article
sources DOAJ
author Liping Qu
Didi Li
Xiaoping Gao
Yongwei Li
Jianming Wu
Wenjun Zou
spellingShingle Liping Qu
Didi Li
Xiaoping Gao
Yongwei Li
Jianming Wu
Wenjun Zou
Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
Frontiers in Pharmacology
Di’ao Xinxuekang
LDL-C
PCSK9
LDLR
ApoE–/– mice
author_facet Liping Qu
Didi Li
Xiaoping Gao
Yongwei Li
Jianming Wu
Wenjun Zou
author_sort Liping Qu
title Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
title_short Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
title_full Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
title_fullStr Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
title_full_unstemmed Di’ao Xinxuekang Capsule, a Chinese Medicinal Product, Decreases Serum Lipids Levels in High-Fat Diet-Fed ApoE–/– Mice by Downregulating PCSK9
title_sort di’ao xinxuekang capsule, a chinese medicinal product, decreases serum lipids levels in high-fat diet-fed apoe–/– mice by downregulating pcsk9
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2018-11-01
description Numerous risk factors are responsible for the development of atherosclerosis, for which an increased serum level of low-density lipoprotein cholesterol (LDL-C) is a driving force. By binding to the low-density lipoprotein cholesterol receptor (LDLR) and inducing LDLR degradation, proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis regulation. The inducement of PCSK9 expression is also an important reason for statin intolerance. The Di’ao Xinxuekang (DXXK) capsule extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product used in atherosclerotic cardiovascular disease. Although DXXK has been widely used in atherosclerotic cardiovascular treatment for nearly 30 years, studies on the potential mechanisms of the lipid-lowering effect are very limited. The purpose of the present study was to demonstrate the possible involvement of the PCSK9/LDLR signaling pathway in the lipid-lowering and antiatherosclerotic effect of DXXK in high-fat diet-fed ApoE–/– mice. The results showed that DXXK treatment alleviated hyperlipidemia, fat accumulation, and atherosclerosis formation in ApoE–/– mice. Furthermore, changes in the expression of PCSK9 mRNA in liver tissue and the circulating PCSK9 level in ApoE–/– mice were both reversed after DXXK treatment, and upregulation of LDLR in the liver was also detected in the protein level in DXXK-treated mice. Our study is the first to show that DXXK could alleviate lipid disorder and ameliorate atherosclerosis with downregulation of the PCSK9 in high-fat diet-fed ApoE–/– mice, suggesting that DXXK may be a potential novel therapeutic treatment and may support statin action in the treatment of atherosclerosis.
topic Di’ao Xinxuekang
LDL-C
PCSK9
LDLR
ApoE–/– mice
url https://www.frontiersin.org/article/10.3389/fphar.2018.01170/full
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AT didili diaoxinxuekangcapsuleachinesemedicinalproductdecreasesserumlipidslevelsinhighfatdietfedapoemicebydownregulatingpcsk9
AT xiaopinggao diaoxinxuekangcapsuleachinesemedicinalproductdecreasesserumlipidslevelsinhighfatdietfedapoemicebydownregulatingpcsk9
AT yongweili diaoxinxuekangcapsuleachinesemedicinalproductdecreasesserumlipidslevelsinhighfatdietfedapoemicebydownregulatingpcsk9
AT jianmingwu diaoxinxuekangcapsuleachinesemedicinalproductdecreasesserumlipidslevelsinhighfatdietfedapoemicebydownregulatingpcsk9
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