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Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice

Dihydroarteannuin (DHA), the primary element of artemisinin extracted from the traditional Chinese herb Artemisia annua L., has been used in malaria treatment for a long time. Recently, many studies have indicated that DHA also exhibits potent anti-rheumatoid arthritis (RA) activity. In this study,...

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Autores principales: Zhang, Mingying, Wu, Danbin, Xu, Jia, Liu, Lijuan, Jiao, Wei, Yu, Jiahui, Chen, Guangxing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091180/
https://www.ncbi.nlm.nih.gov/pubmed/35571141
http://dx.doi.org/10.3389/fphar.2022.884881
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author Zhang, Mingying
Wu, Danbin
Xu, Jia
Liu, Lijuan
Jiao, Wei
Yu, Jiahui
Chen, Guangxing
author_facet Zhang, Mingying
Wu, Danbin
Xu, Jia
Liu, Lijuan
Jiao, Wei
Yu, Jiahui
Chen, Guangxing
author_sort Zhang, Mingying
collection PubMed
description Dihydroarteannuin (DHA), the primary element of artemisinin extracted from the traditional Chinese herb Artemisia annua L., has been used in malaria treatment for a long time. Recently, many studies have indicated that DHA also exhibits potent anti-rheumatoid arthritis (RA) activity. In this study, collagen-induced arthritis (CIA) in DBA/1J mice and inflammatory model in THP-1 cells were established to evaluate the modulatory effects of DHA on joint destruction and to explore the underlying mechanisms. Our results showed that DHA decreased the serum levels of IL-1β and IL-6, alleviated paw oedema, and reduced bone destruction in DBA/1J mice with CIA. Further exploration with the inflammatory model in THP-1 cells indicated that DHA reduced the protein expression of hypoxia‐inducible factor (HIF)‐1α and the phosphorylation in Janus kinase (JAK) 3 and signal transducer and activator of transcription (STAT) 3 protein, which resulted in a decrease in NOD-like receptor protein (NLRP) 3 expression and interleukin (IL)-1β release. Consequentially, the inflammatory activation in THP-1 cells was inhibited. Therefore, we concluded that DHA efficiently alleviated the inflammation and arthritic symptoms in CIA mice and downregulated inflammation in part by inhibiting NLRP3 expression via the HIF‐1α and JAK3/STAT3 signaling pathway. Thus, DHA may be considered as a potential therapeutic agent in RA treatment.
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spelling pubmed-90911802022-05-12 Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice Zhang, Mingying Wu, Danbin Xu, Jia Liu, Lijuan Jiao, Wei Yu, Jiahui Chen, Guangxing Front Pharmacol Pharmacology Dihydroarteannuin (DHA), the primary element of artemisinin extracted from the traditional Chinese herb Artemisia annua L., has been used in malaria treatment for a long time. Recently, many studies have indicated that DHA also exhibits potent anti-rheumatoid arthritis (RA) activity. In this study, collagen-induced arthritis (CIA) in DBA/1J mice and inflammatory model in THP-1 cells were established to evaluate the modulatory effects of DHA on joint destruction and to explore the underlying mechanisms. Our results showed that DHA decreased the serum levels of IL-1β and IL-6, alleviated paw oedema, and reduced bone destruction in DBA/1J mice with CIA. Further exploration with the inflammatory model in THP-1 cells indicated that DHA reduced the protein expression of hypoxia‐inducible factor (HIF)‐1α and the phosphorylation in Janus kinase (JAK) 3 and signal transducer and activator of transcription (STAT) 3 protein, which resulted in a decrease in NOD-like receptor protein (NLRP) 3 expression and interleukin (IL)-1β release. Consequentially, the inflammatory activation in THP-1 cells was inhibited. Therefore, we concluded that DHA efficiently alleviated the inflammation and arthritic symptoms in CIA mice and downregulated inflammation in part by inhibiting NLRP3 expression via the HIF‐1α and JAK3/STAT3 signaling pathway. Thus, DHA may be considered as a potential therapeutic agent in RA treatment. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9091180/ /pubmed/35571141 http://dx.doi.org/10.3389/fphar.2022.884881 Text en Copyright © 2022 Zhang, Wu, Xu, Liu, Jiao, Yu and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Mingying
Wu, Danbin
Xu, Jia
Liu, Lijuan
Jiao, Wei
Yu, Jiahui
Chen, Guangxing
Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title_full Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title_fullStr Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title_full_unstemmed Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title_short Suppression of NLRP3 Inflammasome by Dihydroarteannuin via the HIF‐1α and JAK3/STAT3 Signaling Pathway Contributes to Attenuation of Collagen-Induced Arthritis in Mice
title_sort suppression of nlrp3 inflammasome by dihydroarteannuin via the hif‐1α and jak3/stat3 signaling pathway contributes to attenuation of collagen-induced arthritis in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091180/
https://www.ncbi.nlm.nih.gov/pubmed/35571141
http://dx.doi.org/10.3389/fphar.2022.884881
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