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Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells
Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human um...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059859/ https://www.ncbi.nlm.nih.gov/pubmed/27584788 http://dx.doi.org/10.1038/cddis.2016.255 |
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author | Han, Qiao Bing, Wang Di, Yin Hua, Li Shi-he, Li Yu-hua, Zheng Xiu-guo, Han Yu-gang, Wang Qi-ming, Fan Shih-mo, Yang Ting-ting, Tang |
author_facet | Han, Qiao Bing, Wang Di, Yin Hua, Li Shi-he, Li Yu-hua, Zheng Xiu-guo, Han Yu-gang, Wang Qi-ming, Fan Shih-mo, Yang Ting-ting, Tang |
author_sort | Han, Qiao |
collection | PubMed |
description | Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKβ kinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically. |
format | Online Article Text |
id | pubmed-5059859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50598592016-10-26 Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells Han, Qiao Bing, Wang Di, Yin Hua, Li Shi-he, Li Yu-hua, Zheng Xiu-guo, Han Yu-gang, Wang Qi-ming, Fan Shih-mo, Yang Ting-ting, Tang Cell Death Dis Original Article Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKβ kinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically. Nature Publishing Group 2016-09 2016-09-01 /pmc/articles/PMC5059859/ /pubmed/27584788 http://dx.doi.org/10.1038/cddis.2016.255 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Han, Qiao Bing, Wang Di, Yin Hua, Li Shi-he, Li Yu-hua, Zheng Xiu-guo, Han Yu-gang, Wang Qi-ming, Fan Shih-mo, Yang Ting-ting, Tang Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title | Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title_full | Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title_fullStr | Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title_full_unstemmed | Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title_short | Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells |
title_sort | kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating nf-κb signaling in macrophages and protecting endothelial cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059859/ https://www.ncbi.nlm.nih.gov/pubmed/27584788 http://dx.doi.org/10.1038/cddis.2016.255 |
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