Cargando…

Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lacto...

Descripción completa

Detalles Bibliográficos
Autores principales: Linghu, Ke-Gang, Zhao, Guan-Ding, Zhang, Dai-Yan, Xiong, Shi-Hang, Wu, Guo-Ping, Shen, Li-Yu, Cui, Wen-Qing, Zhang, Tian, Hu, Yuan-Jia, Guo, Bing, Shen, Xiang-Chun, Yu, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222175/
https://www.ncbi.nlm.nih.gov/pubmed/37241980
http://dx.doi.org/10.3390/molecules28104241
_version_ 1785049634282930176
author Linghu, Ke-Gang
Zhao, Guan-Ding
Zhang, Dai-Yan
Xiong, Shi-Hang
Wu, Guo-Ping
Shen, Li-Yu
Cui, Wen-Qing
Zhang, Tian
Hu, Yuan-Jia
Guo, Bing
Shen, Xiang-Chun
Yu, Hua
author_facet Linghu, Ke-Gang
Zhao, Guan-Ding
Zhang, Dai-Yan
Xiong, Shi-Hang
Wu, Guo-Ping
Shen, Li-Yu
Cui, Wen-Qing
Zhang, Tian
Hu, Yuan-Jia
Guo, Bing
Shen, Xiang-Chun
Yu, Hua
author_sort Linghu, Ke-Gang
collection PubMed
description Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1β-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs.
format Online
Article
Text
id pubmed-10222175
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102221752023-05-28 Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB Linghu, Ke-Gang Zhao, Guan-Ding Zhang, Dai-Yan Xiong, Shi-Hang Wu, Guo-Ping Shen, Li-Yu Cui, Wen-Qing Zhang, Tian Hu, Yuan-Jia Guo, Bing Shen, Xiang-Chun Yu, Hua Molecules Article Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1β-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs. MDPI 2023-05-22 /pmc/articles/PMC10222175/ /pubmed/37241980 http://dx.doi.org/10.3390/molecules28104241 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Linghu, Ke-Gang
Zhao, Guan-Ding
Zhang, Dai-Yan
Xiong, Shi-Hang
Wu, Guo-Ping
Shen, Li-Yu
Cui, Wen-Qing
Zhang, Tian
Hu, Yuan-Jia
Guo, Bing
Shen, Xiang-Chun
Yu, Hua
Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title_full Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title_fullStr Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title_full_unstemmed Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title_short Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB
title_sort leocarpinolide b attenuates collagen type ii-induced arthritis by inhibiting dna binding activity of nf-κb
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222175/
https://www.ncbi.nlm.nih.gov/pubmed/37241980
http://dx.doi.org/10.3390/molecules28104241
work_keys_str_mv AT linghukegang leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT zhaoguanding leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT zhangdaiyan leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT xiongshihang leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT wuguoping leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT shenliyu leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT cuiwenqing leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT zhangtian leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT huyuanjia leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT guobing leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT shenxiangchun leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb
AT yuhua leocarpinolidebattenuatescollagentypeiiinducedarthritisbyinhibitingdnabindingactivityofnfkb