Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (...

Full description

Saved in:
Bibliographic Details
Main Authors: Su-Bin Kwak, Sushruta Koppula, Eun-Jung In, Xiao Sun, Young-Kyu Kim, Myong-Ki Kim, Kwang-Ho Lee, Tae-Bong Kang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/6054069
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850172823389077504
author Su-Bin Kwak
Sushruta Koppula
Eun-Jung In
Xiao Sun
Young-Kyu Kim
Myong-Ki Kim
Kwang-Ho Lee
Tae-Bong Kang
author_facet Su-Bin Kwak
Sushruta Koppula
Eun-Jung In
Xiao Sun
Young-Kyu Kim
Myong-Ki Kim
Kwang-Ho Lee
Tae-Bong Kang
author_sort Su-Bin Kwak
collection DOAJ
description Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1β levels, significantly (p<0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.
format Article
id doaj-art-ccbc4a038f9746b88c0e34f2c30174b6
institution OA Journals
issn 0962-9351
1466-1861
language English
publishDate 2018-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-ccbc4a038f9746b88c0e34f2c30174b62025-08-20T02:19:58ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/60540696054069Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC PhosphorylationSu-Bin Kwak0Sushruta Koppula1Eun-Jung In2Xiao Sun3Young-Kyu Kim4Myong-Ki Kim5Kwang-Ho Lee6Tae-Bong Kang7Department of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Food Science and Engineering, Seowon University, Cheongju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaDepartment of Applied Life Science, Graduate School, Konkuk University, Chungju, Republic of KoreaArtemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1β levels, significantly (p<0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.http://dx.doi.org/10.1155/2018/6054069
spellingShingle Su-Bin Kwak
Sushruta Koppula
Eun-Jung In
Xiao Sun
Young-Kyu Kim
Myong-Ki Kim
Kwang-Ho Lee
Tae-Bong Kang
Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
Mediators of Inflammation
title Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
title_full Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
title_fullStr Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
title_full_unstemmed Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
title_short Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation
title_sort artemisia extract suppresses nlrp3 and aim2 inflammasome activation by inhibition of asc phosphorylation
url http://dx.doi.org/10.1155/2018/6054069
work_keys_str_mv AT subinkwak artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT sushrutakoppula artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT eunjungin artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT xiaosun artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT youngkyukim artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT myongkikim artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT kwangholee artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation
AT taebongkang artemisiaextractsuppressesnlrp3andaim2inflammasomeactivationbyinhibitionofascphosphorylation