Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes

The discovery of alternative medicines with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Phillyrin (Phil), the predominant lignan glycoside of Forsythia suspensa, has been reported to exert several pharmacological effects, such as antivirus, anti-inflammation, anti-oxidati...

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Main Authors: Gang Chen, Yuhang Mao, Jing Wang, Junnan Zhou, Li Diao, Sirui Wang, Wenjuan Zhao, Xinyi Zhu, Xiaolu Yu, Fuli Zhao, Xuan Liu, Mei Liu
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Arabian Journal of Chemistry
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1878535223003064
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author Gang Chen
Yuhang Mao
Jing Wang
Junnan Zhou
Li Diao
Sirui Wang
Wenjuan Zhao
Xinyi Zhu
Xiaolu Yu
Fuli Zhao
Xuan Liu
Mei Liu
author_facet Gang Chen
Yuhang Mao
Jing Wang
Junnan Zhou
Li Diao
Sirui Wang
Wenjuan Zhao
Xinyi Zhu
Xiaolu Yu
Fuli Zhao
Xuan Liu
Mei Liu
author_sort Gang Chen
collection DOAJ
description The discovery of alternative medicines with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Phillyrin (Phil), the predominant lignan glycoside of Forsythia suspensa, has been reported to exert several pharmacological effects, such as antivirus, anti-inflammation, anti-oxidation, anti-obesity, and antipyretic activity. However, the effect of Phil on RA remains unknown. In this study, We utilized both in vivo collagen-induced arthritis (CIA) rat models and in vitro TNFα-induced fibroblast-like synoviocytes (FLSs) to study the inhibitory effects of Phil on RA. The in vivo studies revealed that Phil treatment effectively ameliorated synovial inflammation and bone erosion in CIA rats. The in vitro studies demonstrated that Phil could significantly suppress the proliferation and migration of arthritic FLSs. In addition, treatment with Phil resulted in decreased mRNA expression of proinflammatory cytokines including TNFα, IL-1β, IL-6, IL-8 and MMP9. Molecular mechanistic investigations revealed that the suppressive effects of Phil were mediated by blockade of the MAPK (ERK, p38, and JNK) and NF-κB pathways. Taken together, our findings suggest that Phil has an anti-arthritic effect in CIA rats by inhibiting the pathogenic characteristic of arthritic FLSs throught suppression of NF-κB and MAPKs signaling pathways. These results demonstrate the potential of Phil as a novel therapeutic agent for the treatment of RA.
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spelling doaj.art-6d0a5c2397934aa487eeee3a4cd67f512023-06-15T04:54:43ZengElsevierArabian Journal of Chemistry1878-53522023-08-01168104844Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytesGang Chen0Yuhang Mao1Jing Wang2Junnan Zhou3Li Diao4Sirui Wang5Wenjuan Zhao6Xinyi Zhu7Xiaolu Yu8Fuli Zhao9Xuan Liu10Mei Liu11Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaJiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaCorresponding author.; Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210023, ChinaThe discovery of alternative medicines with less adverse effects is extremely urgent for rheumatoid arthritis (RA). Phillyrin (Phil), the predominant lignan glycoside of Forsythia suspensa, has been reported to exert several pharmacological effects, such as antivirus, anti-inflammation, anti-oxidation, anti-obesity, and antipyretic activity. However, the effect of Phil on RA remains unknown. In this study, We utilized both in vivo collagen-induced arthritis (CIA) rat models and in vitro TNFα-induced fibroblast-like synoviocytes (FLSs) to study the inhibitory effects of Phil on RA. The in vivo studies revealed that Phil treatment effectively ameliorated synovial inflammation and bone erosion in CIA rats. The in vitro studies demonstrated that Phil could significantly suppress the proliferation and migration of arthritic FLSs. In addition, treatment with Phil resulted in decreased mRNA expression of proinflammatory cytokines including TNFα, IL-1β, IL-6, IL-8 and MMP9. Molecular mechanistic investigations revealed that the suppressive effects of Phil were mediated by blockade of the MAPK (ERK, p38, and JNK) and NF-κB pathways. Taken together, our findings suggest that Phil has an anti-arthritic effect in CIA rats by inhibiting the pathogenic characteristic of arthritic FLSs throught suppression of NF-κB and MAPKs signaling pathways. These results demonstrate the potential of Phil as a novel therapeutic agent for the treatment of RA.http://www.sciencedirect.com/science/article/pii/S1878535223003064PhillyrinRheumatoid arthritisCollagen-induced arthritisFibroblast-like synoviocyte
spellingShingle Gang Chen
Yuhang Mao
Jing Wang
Junnan Zhou
Li Diao
Sirui Wang
Wenjuan Zhao
Xinyi Zhu
Xiaolu Yu
Fuli Zhao
Xuan Liu
Mei Liu
Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
Arabian Journal of Chemistry
Phillyrin
Rheumatoid arthritis
Collagen-induced arthritis
Fibroblast-like synoviocyte
title Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
title_full Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
title_fullStr Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
title_full_unstemmed Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
title_short Phillyrin ameliorated collagen-induced arthritis through inhibition of NF-κB and MAPKs pathways in fibroblast-like synoviocytes
title_sort phillyrin ameliorated collagen induced arthritis through inhibition of nf κb and mapks pathways in fibroblast like synoviocytes
topic Phillyrin
Rheumatoid arthritis
Collagen-induced arthritis
Fibroblast-like synoviocyte
url http://www.sciencedirect.com/science/article/pii/S1878535223003064
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