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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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 |
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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 |
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