Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization

Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and...

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Main Authors: Yinhe Cai, Junmao Wen, Siwen Ma, Zhexing Mai, Qunzhang Zhan, Yijun Wang, Yueyao Zhang, He Chen, Haiyi Li, Wei Wu, Rong Li, Chuanjin Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2021.666449/full
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author Yinhe Cai
Junmao Wen
Siwen Ma
Zhexing Mai
Qunzhang Zhan
Yijun Wang
Yueyao Zhang
He Chen
Haiyi Li
Wei Wu
Rong Li
Chuanjin Luo
author_facet Yinhe Cai
Junmao Wen
Siwen Ma
Zhexing Mai
Qunzhang Zhan
Yijun Wang
Yueyao Zhang
He Chen
Haiyi Li
Wei Wu
Rong Li
Chuanjin Luo
author_sort Yinhe Cai
collection DOAJ
description Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE−/− mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1β levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1β, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.
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spelling doaj.art-fabece2db3714d34a9781c81249b58032022-12-21T21:28:47ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-09-011210.3389/fphys.2021.666449666449Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage PolarizationYinhe Cai0Junmao Wen1Siwen Ma2Zhexing Mai3Qunzhang Zhan4Yijun Wang5Yueyao Zhang6He Chen7Haiyi Li8Wei Wu9Rong Li10Chuanjin Luo11First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaFirst Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaMacrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE−/− mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1β levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1β, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.https://www.frontiersin.org/articles/10.3389/fphys.2021.666449/fullHuang-Lian-Jie-Du decoctionatherosclerosisplaque stabilitymacrophages polarizationApoE−/− mice
spellingShingle Yinhe Cai
Junmao Wen
Siwen Ma
Zhexing Mai
Qunzhang Zhan
Yijun Wang
Yueyao Zhang
He Chen
Haiyi Li
Wei Wu
Rong Li
Chuanjin Luo
Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
Frontiers in Physiology
Huang-Lian-Jie-Du decoction
atherosclerosis
plaque stability
macrophages polarization
ApoE−/− mice
title Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
title_full Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
title_fullStr Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
title_full_unstemmed Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
title_short Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization
title_sort huang lian jie du decoction attenuates atherosclerosis and increases plaque stability in high fat diet induced apoe mice by inhibiting m1 macrophage polarization and promoting m2 macrophage polarization
topic Huang-Lian-Jie-Du decoction
atherosclerosis
plaque stability
macrophages polarization
ApoE−/− mice
url https://www.frontiersin.org/articles/10.3389/fphys.2021.666449/full
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