<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways

<i>Caragana rosea</i> Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflamm...

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Autores principales:	Ankita Mitra, Akash Ahuja, Laily Rahmawati, Han Gyung Kim, Byoung Young Woo, Yong Deog Hong, Mohammad Amjad Hossain, Zhiyun Zhang, Soo-Yong Kim, Jongsung Lee, Jong-Hoon Kim, Jae Youl Cho
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Caragana rosea</i> Turcz (Cr-ME) anti-inflammatory activity NF-κB and IRF3 signaling pathways Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/0ecd742ac97e49f9bc11de78156425ce
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spelling	oai:doaj.org-article:0ecd742ac97e49f9bc11de78156425ce2021-11-11T18:37:26Z<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways10.3390/molecules262166601420-3049https://doaj.org/article/0ecd742ac97e49f9bc11de78156425ce2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6660https://doaj.org/toc/1420-3049<i>Caragana rosea</i> Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of <i>Caragana rosea</i> (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/β and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.Ankita MitraAkash AhujaLaily RahmawatiHan Gyung KimByoung Young WooYong Deog HongMohammad Amjad HossainZhiyun ZhangSoo-Yong KimJongsung LeeJong-Hoon KimJae Youl ChoMDPI AGarticle<i>Caragana rosea</i> Turcz (Cr-ME)anti-inflammatory activityNF-κB and IRF3 signaling pathwaysOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6660, p 6660 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Caragana rosea</i> Turcz (Cr-ME) anti-inflammatory activity NF-κB and IRF3 signaling pathways Organic chemistry QD241-441
spellingShingle	<i>Caragana rosea</i> Turcz (Cr-ME) anti-inflammatory activity NF-κB and IRF3 signaling pathways Organic chemistry QD241-441 Ankita Mitra Akash Ahuja Laily Rahmawati Han Gyung Kim Byoung Young Woo Yong Deog Hong Mohammad Amjad Hossain Zhiyun Zhang Soo-Yong Kim Jongsung Lee Jong-Hoon Kim Jae Youl Cho <i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
description	<i>Caragana rosea</i> Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of <i>Caragana rosea</i> (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/β and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.
format	article
author	Ankita Mitra Akash Ahuja Laily Rahmawati Han Gyung Kim Byoung Young Woo Yong Deog Hong Mohammad Amjad Hossain Zhiyun Zhang Soo-Yong Kim Jongsung Lee Jong-Hoon Kim Jae Youl Cho
author_facet	Ankita Mitra Akash Ahuja Laily Rahmawati Han Gyung Kim Byoung Young Woo Yong Deog Hong Mohammad Amjad Hossain Zhiyun Zhang Soo-Yong Kim Jongsung Lee Jong-Hoon Kim Jae Youl Cho
author_sort	Ankita Mitra
title	<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
title_short	<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
title_full	<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
title_fullStr	<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
title_full_unstemmed	<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways
title_sort	<i>caragana rosea</i> turcz methanol extract inhibits lipopolysaccharide-induced inflammatory responses by suppressing the tlr4/nf-κb/irf3 signaling pathways
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0ecd742ac97e49f9bc11de78156425ce
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<i>Caragana rosea</i> Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways

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