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Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes

MASM is a matrine derivate that exhibits a number of pharmacological effects, including immunosuppressive activity and anti-inflammatory properties. In this study, the mechanisms underlying the therapeutic efficacy of MASM in the treatment of rheumatoid arthritis were investigated using DBA/1 mice w...

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Autores principales: Zou, Yuming, Li, Quan, Liu, Denghui, Li, Jia, Cai, Qing, Li, Chao, Zhao, Qingjie, Xu, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446426/
https://www.ncbi.nlm.nih.gov/pubmed/28550307
http://dx.doi.org/10.1038/s41598-017-02423-7
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author Zou, Yuming
Li, Quan
Liu, Denghui
Li, Jia
Cai, Qing
Li, Chao
Zhao, Qingjie
Xu, Weidong
author_facet Zou, Yuming
Li, Quan
Liu, Denghui
Li, Jia
Cai, Qing
Li, Chao
Zhao, Qingjie
Xu, Weidong
author_sort Zou, Yuming
collection PubMed
description MASM is a matrine derivate that exhibits a number of pharmacological effects, including immunosuppressive activity and anti-inflammatory properties. In this study, the mechanisms underlying the therapeutic efficacy of MASM in the treatment of rheumatoid arthritis were investigated using DBA/1 mice with collagen-induced arthritis (CIA) and fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLS). We demonstrated that MASM markedly attenuated the severity of arthritis in CIA mice. The therapeutic effects were associated with ameliorated joint swelling and reduced bone erosion and destruction. Furthermore, the administration of MASM suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In vitro, MASM inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) and matrix metalloproteinases (MMP-1, MMP-3 and MMP-13) by inhibiting both the phosphorylation of MAPKs and the activation of NF-κB in IL-1β-stimulated RA-FLS. Additionally, MASM could induce apoptosis of RA-FLS via mitochondrial and Akt signaling pathways in human RA-FLS. These findings suggest that MASM could attenuate arthritis severity in CIA mice at least partially by blocking the phosphorylation of MAPKs and the activation of NF-κB and by inducing apoptosis in RA-FLS. MASM could be a potent therapeutic agent for the treatment of RA.
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spelling pubmed-54464262017-05-30 Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes Zou, Yuming Li, Quan Liu, Denghui Li, Jia Cai, Qing Li, Chao Zhao, Qingjie Xu, Weidong Sci Rep Article MASM is a matrine derivate that exhibits a number of pharmacological effects, including immunosuppressive activity and anti-inflammatory properties. In this study, the mechanisms underlying the therapeutic efficacy of MASM in the treatment of rheumatoid arthritis were investigated using DBA/1 mice with collagen-induced arthritis (CIA) and fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLS). We demonstrated that MASM markedly attenuated the severity of arthritis in CIA mice. The therapeutic effects were associated with ameliorated joint swelling and reduced bone erosion and destruction. Furthermore, the administration of MASM suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In vitro, MASM inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) and matrix metalloproteinases (MMP-1, MMP-3 and MMP-13) by inhibiting both the phosphorylation of MAPKs and the activation of NF-κB in IL-1β-stimulated RA-FLS. Additionally, MASM could induce apoptosis of RA-FLS via mitochondrial and Akt signaling pathways in human RA-FLS. These findings suggest that MASM could attenuate arthritis severity in CIA mice at least partially by blocking the phosphorylation of MAPKs and the activation of NF-κB and by inducing apoptosis in RA-FLS. MASM could be a potent therapeutic agent for the treatment of RA. Nature Publishing Group UK 2017-05-26 /pmc/articles/PMC5446426/ /pubmed/28550307 http://dx.doi.org/10.1038/s41598-017-02423-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zou, Yuming
Li, Quan
Liu, Denghui
Li, Jia
Cai, Qing
Li, Chao
Zhao, Qingjie
Xu, Weidong
Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title_full Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title_fullStr Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title_full_unstemmed Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title_short Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
title_sort therapeutic effects of matrine derivate masm in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446426/
https://www.ncbi.nlm.nih.gov/pubmed/28550307
http://dx.doi.org/10.1038/s41598-017-02423-7
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