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Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts

BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolid...

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Autores principales: Kusunoki, Natsuko, Yamazaki, Ryuta, Kitasato, Hidero, Beppu, Moroe, Aoki, Haruhito, Kawai, Shinichi
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC373449/
https://www.ncbi.nlm.nih.gov/pubmed/15040811
http://dx.doi.org/10.1186/1471-2210-4-2
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author Kusunoki, Natsuko
Yamazaki, Ryuta
Kitasato, Hidero
Beppu, Moroe
Aoki, Haruhito
Kawai, Shinichi
author_facet Kusunoki, Natsuko
Yamazaki, Ryuta
Kitasato, Hidero
Beppu, Moroe
Aoki, Haruhito
Kawai, Shinichi
author_sort Kusunoki, Natsuko
collection PubMed
description BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis. RESULTS: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and by 5-bromo-2'-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor (PPAR) γ was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARγ activation was induced by 15-deoxy-Δ(12,14)-prostaglandin J(2), triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF. CONCLUSION: The mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA.
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spelling pubmed-3734492004-03-21 Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts Kusunoki, Natsuko Yamazaki, Ryuta Kitasato, Hidero Beppu, Moroe Aoki, Haruhito Kawai, Shinichi BMC Pharmacol Research Article BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis. RESULTS: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and by 5-bromo-2'-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor (PPAR) γ was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARγ activation was induced by 15-deoxy-Δ(12,14)-prostaglandin J(2), triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF. CONCLUSION: The mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA. BioMed Central 2004-02-17 /pmc/articles/PMC373449/ /pubmed/15040811 http://dx.doi.org/10.1186/1471-2210-4-2 Text en Copyright © 2004 Kusunoki et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research Article
Kusunoki, Natsuko
Yamazaki, Ryuta
Kitasato, Hidero
Beppu, Moroe
Aoki, Haruhito
Kawai, Shinichi
Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title_full Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title_fullStr Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title_full_unstemmed Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title_short Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
title_sort triptolide, an active compound identified in a traditional chinese herb, induces apoptosis of rheumatoid synovial fibroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC373449/
https://www.ncbi.nlm.nih.gov/pubmed/15040811
http://dx.doi.org/10.1186/1471-2210-4-2
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