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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Autores principales: Li Wang, Tong Wu, Chunying Si, He Wang, Ke Yue, Shasha Shang, Xiaohui Li, Yushan Chen, Huaimin Guan
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/bf6afad25e8449d7a812bff9b5448a7f
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spelling oai:doaj.org-article:bf6afad25e8449d7a812bff9b5448a7f2021-11-18T09:40:11ZDanlou Tablet Activates Autophagy of Vascular Adventitial Fibroblasts Through PI3K/Akt/mTOR to Protect Cells From Damage Caused by Atherosclerosis1663-981210.3389/fphar.2021.730525https://doaj.org/article/bf6afad25e8449d7a812bff9b5448a7f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.730525/fullhttps://doaj.org/toc/1663-9812Danlou 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.Li WangTong WuChunying SiHe WangKe YueShasha ShangXiaohui LiYushan ChenHuaimin GuanFrontiers Media S.A.articleatherosclerosisdanlou tabletautophagyPI3K/AKT/mTORChinese patent medicineTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic atherosclerosis
danlou tablet
autophagy
PI3K/AKT/mTOR
Chinese patent medicine
Therapeutics. Pharmacology
RM1-950
spellingShingle atherosclerosis
danlou tablet
autophagy
PI3K/AKT/mTOR
Chinese patent medicine
Therapeutics. Pharmacology
RM1-950
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
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.
format article
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
title 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_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_sort danlou tablet activates autophagy of vascular adventitial fibroblasts through pi3k/akt/mtor to protect cells from damage caused by atherosclerosis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/bf6afad25e8449d7a812bff9b5448a7f
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