Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis

Danlou tablet (DLT), a commercial Chinese patent medicine, has been widely used to treat cardiovascular diseases for many years. Atherosclerosis (AS) is the leading cause of cardiovascular disease. Increasing evidence indicates that autophagy plays a vital role in the development of AS. Here we inve...

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Main Authors: Li Wang, Tong Wu, Chunying Si, He Wang, Ke Yue, Shasha Shang, Xiaohui Li, Yushan Chen, Huaimin Guan
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.730525/full
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author Li Wang
Tong Wu
Chunying Si
He Wang
Ke Yue
Shasha Shang
Xiaohui Li
Yushan Chen
Huaimin Guan
author_facet Li Wang
Tong Wu
Chunying Si
He Wang
Ke Yue
Shasha Shang
Xiaohui Li
Yushan Chen
Huaimin Guan
author_sort Li Wang
collection DOAJ
description Danlou tablet (DLT), a commercial Chinese patent medicine, has been widely used to treat cardiovascular diseases for many years. Atherosclerosis (AS) is the leading cause of cardiovascular disease. Increasing evidence indicates that autophagy plays a vital role in the development of AS. Here we investigated whether DLT could activate autophagy to improve AS and further clarified its underlying mechanisms. In an ApoE−/− mice model, the results of Oil red O, Masson’s trichrome, and H&E staining techniques showed that DLT significantly inhibited lipid accumulation and fibrosis formation in atherosclerotic plaque tissue. DLT also inhibited serum triglyceride, cholesterol, and low-density lipoprotein levels and suppressed serum levels of inflammatory factors interleukin-6 and tumor necrosis factor-α in ApoE−/− mice. Moreover, DLT suppressed proliferation, migration, and invasion of human vascular adventitial fibroblasts (HVAFs) by inhibiting the PI3K/Akt/mTOR pathway. In addition, western blot analysis showed that Danlou tablet treatment decreased the expression of p62 and increased Beclin 1 and LC3 I -to-LC3 II ratios in HVAFs. The role of autophagy in treating atherosclerosis by DLT is confirmed by 3-methyladenine (autophagy inhibitor) and rapamycin (autophagy activator) in HVAFs. In summary, DLT activated PI3K/Akt/mTOR-mediated autophagy of vascular adventitial fibroblasts to protect cells from damage caused by atherosclerosis.
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spelling doaj.art-bf6afad25e8449d7a812bff9b5448a7f2022-12-21T21:24:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-11-011210.3389/fphar.2021.730525730525Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by AtherosclerosisLi Wang0Tong Wu1Chunying Si2He Wang3Ke Yue4Shasha Shang5Xiaohui Li6Yushan Chen7Huaimin Guan8Department of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaThe First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, ChinaDanlou tablet (DLT), a commercial Chinese patent medicine, has been widely used to treat cardiovascular diseases for many years. Atherosclerosis (AS) is the leading cause of cardiovascular disease. Increasing evidence indicates that autophagy plays a vital role in the development of AS. Here we investigated whether DLT could activate autophagy to improve AS and further clarified its underlying mechanisms. In an ApoE−/− mice model, the results of Oil red O, Masson’s trichrome, and H&E staining techniques showed that DLT significantly inhibited lipid accumulation and fibrosis formation in atherosclerotic plaque tissue. DLT also inhibited serum triglyceride, cholesterol, and low-density lipoprotein levels and suppressed serum levels of inflammatory factors interleukin-6 and tumor necrosis factor-α in ApoE−/− mice. Moreover, DLT suppressed proliferation, migration, and invasion of human vascular adventitial fibroblasts (HVAFs) by inhibiting the PI3K/Akt/mTOR pathway. In addition, western blot analysis showed that Danlou tablet treatment decreased the expression of p62 and increased Beclin 1 and LC3 I -to-LC3 II ratios in HVAFs. The role of autophagy in treating atherosclerosis by DLT is confirmed by 3-methyladenine (autophagy inhibitor) and rapamycin (autophagy activator) in HVAFs. In summary, DLT activated PI3K/Akt/mTOR-mediated autophagy of vascular adventitial fibroblasts to protect cells from damage caused by atherosclerosis.https://www.frontiersin.org/articles/10.3389/fphar.2021.730525/fullatherosclerosisdanlou tabletautophagyPI3K/AKT/mTORChinese patent medicine
spellingShingle Li Wang
Tong Wu
Chunying Si
He Wang
Ke Yue
Shasha Shang
Xiaohui Li
Yushan Chen
Huaimin Guan
Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
Frontiers in Pharmacology
atherosclerosis
danlou tablet
autophagy
PI3K/AKT/mTOR
Chinese patent medicine
title Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
title_full Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
title_fullStr Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
title_full_unstemmed Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
title_short Danlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis
title_sort danlou tablet activates autophagy of vascular adventitial fibroblasts through pi3k akt mtor to protect cells from damage caused by atherosclerosis
topic atherosclerosis
danlou tablet
autophagy
PI3K/AKT/mTOR
Chinese patent medicine
url https://www.frontiersin.org/articles/10.3389/fphar.2021.730525/full
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