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First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor
Elevated cholesterol significantly increases the risk of developing atherosclerosis and coronary heart disease. The key to treating hypercholesterolemia is lowering plasma cholesterol levels. There have been no studies on the cholesterol-lowering potential of parthenolide (PTL), a naturally occurrin...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572688/ https://www.ncbi.nlm.nih.gov/pubmed/36234807 http://dx.doi.org/10.3390/molecules27196270 |
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author | Liu, Wenjing Liang, Bing Zeng, Jun Meng, Jingsen Shi, Lingyu Yang, Shanbo Chang, Jing Wang, Chao Hu, Xiaokun Wang, Xufu Han, Na Lu, Chenghui Li, Jiao Wang, Congcong Li, Huanting Zhang, Renshuai Xing, Dongming |
author_facet | Liu, Wenjing Liang, Bing Zeng, Jun Meng, Jingsen Shi, Lingyu Yang, Shanbo Chang, Jing Wang, Chao Hu, Xiaokun Wang, Xufu Han, Na Lu, Chenghui Li, Jiao Wang, Congcong Li, Huanting Zhang, Renshuai Xing, Dongming |
author_sort | Liu, Wenjing |
collection | PubMed |
description | Elevated cholesterol significantly increases the risk of developing atherosclerosis and coronary heart disease. The key to treating hypercholesterolemia is lowering plasma cholesterol levels. There have been no studies on the cholesterol-lowering potential of parthenolide (PTL), a naturally occurring small molecule from Tanacetum parthenium. Here, we first put forth PTL’s cholesterol-lowering ability to inhibit cellular uptake of cholesterol in a dose-dependent manner. Its performance was on par with the positive control drug, ezetimibe. Niemann–Pick C1 Like-1 (NPC1L1) has been identified as a potential therapeutic target for hypercholesterolemia. The interaction of PTL with NPC1L1 could be explained by the results of molecular docking and filipin staining further reinforces this hypothesis. Furthermore, PTL reduced the expression of NPC1L1 in HepG2 cells in a concentration-dependent manner, which suggests that PTL functions as a potential NPC1L1 inhibitor with therapeutic potential for hypercholesterolemia. |
format | Online Article Text |
id | pubmed-9572688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95726882022-10-17 First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor Liu, Wenjing Liang, Bing Zeng, Jun Meng, Jingsen Shi, Lingyu Yang, Shanbo Chang, Jing Wang, Chao Hu, Xiaokun Wang, Xufu Han, Na Lu, Chenghui Li, Jiao Wang, Congcong Li, Huanting Zhang, Renshuai Xing, Dongming Molecules Article Elevated cholesterol significantly increases the risk of developing atherosclerosis and coronary heart disease. The key to treating hypercholesterolemia is lowering plasma cholesterol levels. There have been no studies on the cholesterol-lowering potential of parthenolide (PTL), a naturally occurring small molecule from Tanacetum parthenium. Here, we first put forth PTL’s cholesterol-lowering ability to inhibit cellular uptake of cholesterol in a dose-dependent manner. Its performance was on par with the positive control drug, ezetimibe. Niemann–Pick C1 Like-1 (NPC1L1) has been identified as a potential therapeutic target for hypercholesterolemia. The interaction of PTL with NPC1L1 could be explained by the results of molecular docking and filipin staining further reinforces this hypothesis. Furthermore, PTL reduced the expression of NPC1L1 in HepG2 cells in a concentration-dependent manner, which suggests that PTL functions as a potential NPC1L1 inhibitor with therapeutic potential for hypercholesterolemia. MDPI 2022-09-23 /pmc/articles/PMC9572688/ /pubmed/36234807 http://dx.doi.org/10.3390/molecules27196270 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Wenjing Liang, Bing Zeng, Jun Meng, Jingsen Shi, Lingyu Yang, Shanbo Chang, Jing Wang, Chao Hu, Xiaokun Wang, Xufu Han, Na Lu, Chenghui Li, Jiao Wang, Congcong Li, Huanting Zhang, Renshuai Xing, Dongming First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title | First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title_full | First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title_fullStr | First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title_full_unstemmed | First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title_short | First Discovery of Cholesterol-Lowering Activity of Parthenolide as NPC1L1 Inhibitor |
title_sort | first discovery of cholesterol-lowering activity of parthenolide as npc1l1 inhibitor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9572688/ https://www.ncbi.nlm.nih.gov/pubmed/36234807 http://dx.doi.org/10.3390/molecules27196270 |
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