Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to...

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Autores principales:	Jyh-Horng Wang, Kao-Shang Shih, Jing-Ping Liou, Yi-Wen Wu, Anita Shin-Yuan Chang, Kang-Li Wang, Ching-Lin Tsai, Chia-Ron Yang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0b14adf08bc44d2b98428148d6a65951
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spelling	oai:doaj.org-article:0b14adf08bc44d2b98428148d6a659512021-11-18T07:28:00ZAnti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.1932-620310.1371/journal.pone.0031368https://doaj.org/article/0b14adf08bc44d2b98428148d6a659512012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22359588/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol), the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL)-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2), and matrix metalloproteinases (MMPs) by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL). In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg) significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.Jyh-Horng WangKao-Shang ShihJing-Ping LiouYi-Wen WuAnita Shin-Yuan ChangKang-Li WangChing-Lin TsaiChia-Ron YangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31368 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jyh-Horng Wang Kao-Shang Shih Jing-Ping Liou Yi-Wen Wu Anita Shin-Yuan Chang Kang-Li Wang Ching-Lin Tsai Chia-Ron Yang Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
description	Fibroblast-like synoviocytes (FLS) play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs). The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol), the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL)-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2), and matrix metalloproteinases (MMPs) by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL)-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL). In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg) significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.
format	article
author	Jyh-Horng Wang Kao-Shang Shih Jing-Ping Liou Yi-Wen Wu Anita Shin-Yuan Chang Kang-Li Wang Ching-Lin Tsai Chia-Ron Yang
author_facet	Jyh-Horng Wang Kao-Shang Shih Jing-Ping Liou Yi-Wen Wu Anita Shin-Yuan Chang Kang-Li Wang Ching-Lin Tsai Chia-Ron Yang
author_sort	Jyh-Horng Wang
title	Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
title_short	Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
title_full	Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
title_fullStr	Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
title_full_unstemmed	Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
title_sort	anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0b14adf08bc44d2b98428148d6a65951
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Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

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