A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

Abstract Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Mul...

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Autores principales: Ying-Jie Chen, Yu-Xi Liu, Jia-Ying Wu, Chun-Yu Li, Min-Min Tang, Lu Bai, Xiu-Qiong Fu, Jun-Kui Li, Ji-Yao Chou, Cheng-Le Yin, Ya-Ping Wang, Jing-Xuan Bai, Ying Wu, Xiao-Qi Wang, Zhi-Ling Yu
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Science
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Acceso en línea:https://doaj.org/article/b8b6a2d33ebd4bd582bba05d902deac9
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spelling oai:doaj.org-article:b8b6a2d33ebd4bd582bba05d902deac92021-12-02T12:11:50ZA two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes10.1038/s41598-021-83435-22045-2322https://doaj.org/article/b8b6a2d33ebd4bd582bba05d902deac92021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83435-2https://doaj.org/toc/2045-2322Abstract Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.Ying-Jie ChenYu-Xi LiuJia-Ying WuChun-Yu LiMin-Min TangLu BaiXiu-Qiong FuJun-Kui LiJi-Yao ChouCheng-Le YinYa-Ping WangJing-Xuan BaiYing WuXiao-Qi WangZhi-Ling YuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ying-Jie Chen
Yu-Xi Liu
Jia-Ying Wu
Chun-Yu Li
Min-Min Tang
Lu Bai
Xiu-Qiong Fu
Jun-Kui Li
Ji-Yao Chou
Cheng-Le Yin
Ya-Ping Wang
Jing-Xuan Bai
Ying Wu
Xiao-Qi Wang
Zhi-Ling Yu
A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
description Abstract Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.
format article
author Ying-Jie Chen
Yu-Xi Liu
Jia-Ying Wu
Chun-Yu Li
Min-Min Tang
Lu Bai
Xiu-Qiong Fu
Jun-Kui Li
Ji-Yao Chou
Cheng-Le Yin
Ya-Ping Wang
Jing-Xuan Bai
Ying Wu
Xiao-Qi Wang
Zhi-Ling Yu
author_facet Ying-Jie Chen
Yu-Xi Liu
Jia-Ying Wu
Chun-Yu Li
Min-Min Tang
Lu Bai
Xiu-Qiong Fu
Jun-Kui Li
Ji-Yao Chou
Cheng-Le Yin
Ya-Ping Wang
Jing-Xuan Bai
Ying Wu
Xiao-Qi Wang
Zhi-Ling Yu
author_sort Ying-Jie Chen
title A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
title_short A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
title_full A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
title_fullStr A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
title_full_unstemmed A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
title_sort two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b8b6a2d33ebd4bd582bba05d902deac9
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