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Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway
Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In th...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Singapore
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468572/ https://www.ncbi.nlm.nih.gov/pubmed/31937929 http://dx.doi.org/10.1038/s41401-019-0335-4 |
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author | Liu, Qi Zuo, Rui Wang, Kai Nong, Fei-fei Fu, Ya-jun Huang, Shao-wei Pan, Zeng-feng Zhang, Yi Luo, Xia Deng, Xiang-liang Zhang, Xiao-xue Zhou, Lian Chen, Yang |
author_facet | Liu, Qi Zuo, Rui Wang, Kai Nong, Fei-fei Fu, Ya-jun Huang, Shao-wei Pan, Zeng-feng Zhang, Yi Luo, Xia Deng, Xiang-liang Zhang, Xiao-xue Zhou, Lian Chen, Yang |
author_sort | Liu, Qi |
collection | PubMed |
description | Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg(−1) ·d(−1), i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1β and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5–50 μM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC. |
format | Online Article Text |
id | pubmed-7468572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-74685722020-09-03 Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway Liu, Qi Zuo, Rui Wang, Kai Nong, Fei-fei Fu, Ya-jun Huang, Shao-wei Pan, Zeng-feng Zhang, Yi Luo, Xia Deng, Xiang-liang Zhang, Xiao-xue Zhou, Lian Chen, Yang Acta Pharmacol Sin Article Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg(−1) ·d(−1), i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1β and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5–50 μM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC. Springer Singapore 2020-01-14 2020-06 /pmc/articles/PMC7468572/ /pubmed/31937929 http://dx.doi.org/10.1038/s41401-019-0335-4 Text en © CPS and SIMM 2020 |
spellingShingle | Article Liu, Qi Zuo, Rui Wang, Kai Nong, Fei-fei Fu, Ya-jun Huang, Shao-wei Pan, Zeng-feng Zhang, Yi Luo, Xia Deng, Xiang-liang Zhang, Xiao-xue Zhou, Lian Chen, Yang Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title_full | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title_fullStr | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title_full_unstemmed | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title_short | Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway |
title_sort | oroxindin inhibits macrophage nlrp3 inflammasome activation in dss-induced ulcerative colitis in mice via suppressing txnip-dependent nf-κb pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468572/ https://www.ncbi.nlm.nih.gov/pubmed/31937929 http://dx.doi.org/10.1038/s41401-019-0335-4 |
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