An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptos...

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Autores principales:	Yan Zhang, Jian-Ying Wang, Hao Wang, Xiao-Yun Chen, Lei Zhang, Ying Yuan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Rheumatoid arthritis Eucommia ulmoides Oliv. CIA rat Bone metabolism NF-κB signaling pathway Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/da7b3e10506847b4a5342c962b330bd7
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spelling	oai:doaj.org-article:da7b3e10506847b4a5342c962b330bd72021-11-07T12:12:58ZAn alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis10.1186/s13020-021-00522-21749-8546https://doaj.org/article/da7b3e10506847b4a5342c962b330bd72021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00522-2https://doaj.org/toc/1749-8546Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptosis and bone destruction on RA have not been investigated thoroughly. The effects of EF on apoptosis of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells, osteoclast differentiation of RAW264.7 cells, and bone destruction in a collagen-induced arthritis (CIA) model in rats were explored. Methods First, the main components of EF were identified by high-performance liquid chromatography. In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting; we also investigated how EF influenced the differentiation of RAW264.7 cells into osteoclasts. In vivo, we used a rat model of CIA to investigate the effects of EF on anti-arthritis activity, toe swelling, Arthritis Score, serum levels of metabolic bone factors, and pathologic conditions. Micro-computed tomography was used to scan ankle joints. mRNA and protein expression of factors related to the nuclear factor-kappa B (NF-κB) pathway were determined by RT-qPCR and western blotting, respectively. Results EF inhibited synoviocyte proliferation and promoted apoptosis in a dose-dependent manner. EF inhibited osteoclast differentiation by inhibiting activation of the NF-κB pathway. EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicated that EF acted via a mechanism related to bone metabolism induced by the NF-κB pathway. Conclusions EF exerts a potential therapeutic effect upon RA. Our research will help to elucidate the potential pharmacologic mechanisms associated with the beneficial effects of EF, and provide an experimental basis for EF application in clinical treatments. Graphical AbstractYan ZhangJian-Ying WangHao WangXiao-Yun ChenLei ZhangYing YuanBMCarticleRheumatoid arthritisEucommia ulmoides Oliv.CIA ratBone metabolismNF-κB signaling pathwayOther systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rheumatoid arthritis Eucommia ulmoides Oliv. CIA rat Bone metabolism NF-κB signaling pathway Other systems of medicine RZ201-999
spellingShingle	Rheumatoid arthritis Eucommia ulmoides Oliv. CIA rat Bone metabolism NF-κB signaling pathway Other systems of medicine RZ201-999 Yan Zhang Jian-Ying Wang Hao Wang Xiao-Yun Chen Lei Zhang Ying Yuan An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
description	Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptosis and bone destruction on RA have not been investigated thoroughly. The effects of EF on apoptosis of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells, osteoclast differentiation of RAW264.7 cells, and bone destruction in a collagen-induced arthritis (CIA) model in rats were explored. Methods First, the main components of EF were identified by high-performance liquid chromatography. In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting; we also investigated how EF influenced the differentiation of RAW264.7 cells into osteoclasts. In vivo, we used a rat model of CIA to investigate the effects of EF on anti-arthritis activity, toe swelling, Arthritis Score, serum levels of metabolic bone factors, and pathologic conditions. Micro-computed tomography was used to scan ankle joints. mRNA and protein expression of factors related to the nuclear factor-kappa B (NF-κB) pathway were determined by RT-qPCR and western blotting, respectively. Results EF inhibited synoviocyte proliferation and promoted apoptosis in a dose-dependent manner. EF inhibited osteoclast differentiation by inhibiting activation of the NF-κB pathway. EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicated that EF acted via a mechanism related to bone metabolism induced by the NF-κB pathway. Conclusions EF exerts a potential therapeutic effect upon RA. Our research will help to elucidate the potential pharmacologic mechanisms associated with the beneficial effects of EF, and provide an experimental basis for EF application in clinical treatments. Graphical Abstract
format	article
author	Yan Zhang Jian-Ying Wang Hao Wang Xiao-Yun Chen Lei Zhang Ying Yuan
author_facet	Yan Zhang Jian-Ying Wang Hao Wang Xiao-Yun Chen Lei Zhang Ying Yuan
author_sort	Yan Zhang
title	An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
title_short	An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
title_full	An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
title_fullStr	An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
title_full_unstemmed	An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
title_sort	alcohol extract prepared from the male flower of eucommia ulmoides oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/da7b3e10506847b4a5342c962b330bd7
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An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

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