Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways

Abstract Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks o...

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Autores principales: Jiahui Li, Jinglong Pang, Zhe Liu, XianMing Ge, Yanan Zhen, Chen Chen Jiang, Yaming Liu, Qiang Huo, Yiming Sun, Hao Liu
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/74d4539214384343a32c81d3712be7cf
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spelling oai:doaj.org-article:74d4539214384343a32c81d3712be7cf2021-12-02T18:02:23ZShikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways10.1038/s41598-021-97713-62045-2322https://doaj.org/article/74d4539214384343a32c81d3712be7cf2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97713-6https://doaj.org/toc/2045-2322Abstract Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less toxicity to the liver and kidney.Jiahui LiJinglong PangZhe LiuXianMing GeYanan ZhenChen Chen JiangYaming LiuQiang HuoYiming SunHao LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jiahui Li
Jinglong Pang
Zhe Liu
XianMing Ge
Yanan Zhen
Chen Chen Jiang
Yaming Liu
Qiang Huo
Yiming Sun
Hao Liu
Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
description Abstract Shikonin is the main component of the traditional Chinese medicine comfrey, which can inhibit the activity of PKM2 by regulating glycolysis and ATP production. Rheumatoid arthritis synovial cells (RA-FLSs) have been reported to increase glycolytic activity and have other similar hallmarks of metabolic activity. In this study, we investigated the effects of shikonin on glycolysis, mitochondrial function, and cell death in RA-FLSs. The results showed that shikonin induced apoptosis and autophagy in RA-FLSs by activating the production of reactive oxygen species (ROS) and inhibiting intracellular ATP levels, glycolysis-related proteins, and the PI3K-AKT-mTOR signaling pathway. Shikonin can significantly reduce the expression of apoptosis-related proteins, paw swelling in rat arthritic tissues, and the levels of inflammatory factors in peripheral blood, such as TNF-α, IL-6, IL-8, IL-10, IL-17A, and IL-1β while showing less toxicity to the liver and kidney.
format article
author Jiahui Li
Jinglong Pang
Zhe Liu
XianMing Ge
Yanan Zhen
Chen Chen Jiang
Yaming Liu
Qiang Huo
Yiming Sun
Hao Liu
author_facet Jiahui Li
Jinglong Pang
Zhe Liu
XianMing Ge
Yanan Zhen
Chen Chen Jiang
Yaming Liu
Qiang Huo
Yiming Sun
Hao Liu
author_sort Jiahui Li
title Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
title_short Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
title_full Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
title_fullStr Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
title_full_unstemmed Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
title_sort shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/74d4539214384343a32c81d3712be7cf
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AT jinglongpang shikonininducesprogrammeddeathoffibroblastsynovialcellsinrheumatoidarthritisbyinhibitingenergypathways
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