Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation

Xanthatin (XT) is a sesquiterpene lactone isolated from the Chinese herb Xanthium, which belongs to the Asteraceae family. In this study, we developed an inflammation model via stimulating macrophage cell line (RAW 264.7 cells) with lipopolysaccharide (LPS), which was applied to assess the anti-infl...

Full description

Bibliographic Details
Main Authors: Yuanqi Liu, Wenyu Chen, Fang Zheng, Huanan Yu, Kun Wei
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/14/4603
_version_ 1827627628963561472
author Yuanqi Liu
Wenyu Chen
Fang Zheng
Huanan Yu
Kun Wei
author_facet Yuanqi Liu
Wenyu Chen
Fang Zheng
Huanan Yu
Kun Wei
author_sort Yuanqi Liu
collection DOAJ
description Xanthatin (XT) is a sesquiterpene lactone isolated from the Chinese herb Xanthium, which belongs to the Asteraceae family. In this study, we developed an inflammation model via stimulating macrophage cell line (RAW 264.7 cells) with lipopolysaccharide (LPS), which was applied to assess the anti-inflammatory effect and probable mechanisms of xanthatin. When compared with the only LPS-induced group, cells that were pretreated with xanthatin were found to decrease the amount of nitric oxide (NO), reactive oxygen species (ROS) and associated pro-inflammatory factors (TNF-α, IL-1β and IL-6), and downregulate the mRNA expression of iNOS, COX-2, TNF-α, IL-1β, and IL-6. Interestingly, phosphorylated levels of related proteins (STAT3, ERK1/2, SAPK/JNK, IκBα, p65) were notably increased only with the LPS-activated cells, while the expression of these could be reverted by pre-treatment with xanthatin in a dose-dependent way. Meanwhile, xanthatin was also found to block NF-κB p65 from translocating into the nucleus and activating inflammatory gene transcription. Collectively, these results demonstrated that xanthatin suppresses the inflammatory effects through downregulating the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STATs) signaling pathways. Taken together, xanthatin possesses the potential to act as a good anti-inflammatory medication candidate.
first_indexed 2024-03-09T13:17:45Z
format Article
id doaj.art-b5a7ae17b0004aeeb399081209f3b663
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T13:17:45Z
publishDate 2022-07-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-b5a7ae17b0004aeeb399081209f3b6632023-11-30T21:34:32ZengMDPI AGMolecules1420-30492022-07-012714460310.3390/molecules27144603Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs ActivationYuanqi Liu0Wenyu Chen1Fang Zheng2Huanan Yu3Kun Wei4School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaXanthatin (XT) is a sesquiterpene lactone isolated from the Chinese herb Xanthium, which belongs to the Asteraceae family. In this study, we developed an inflammation model via stimulating macrophage cell line (RAW 264.7 cells) with lipopolysaccharide (LPS), which was applied to assess the anti-inflammatory effect and probable mechanisms of xanthatin. When compared with the only LPS-induced group, cells that were pretreated with xanthatin were found to decrease the amount of nitric oxide (NO), reactive oxygen species (ROS) and associated pro-inflammatory factors (TNF-α, IL-1β and IL-6), and downregulate the mRNA expression of iNOS, COX-2, TNF-α, IL-1β, and IL-6. Interestingly, phosphorylated levels of related proteins (STAT3, ERK1/2, SAPK/JNK, IκBα, p65) were notably increased only with the LPS-activated cells, while the expression of these could be reverted by pre-treatment with xanthatin in a dose-dependent way. Meanwhile, xanthatin was also found to block NF-κB p65 from translocating into the nucleus and activating inflammatory gene transcription. Collectively, these results demonstrated that xanthatin suppresses the inflammatory effects through downregulating the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STATs) signaling pathways. Taken together, xanthatin possesses the potential to act as a good anti-inflammatory medication candidate.https://www.mdpi.com/1420-3049/27/14/4603xanthatinRAW 264.7anti-inflammatoryROSNF-κBMAPK
spellingShingle Yuanqi Liu
Wenyu Chen
Fang Zheng
Huanan Yu
Kun Wei
Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
Molecules
xanthatin
RAW 264.7
anti-inflammatory
ROS
NF-κB
MAPK
title Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
title_full Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
title_fullStr Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
title_full_unstemmed Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
title_short Xanthatin Alleviates LPS-Induced Inflammatory Response in RAW264.7 Macrophages by Inhibiting NF-κB, MAPK and STATs Activation
title_sort xanthatin alleviates lps induced inflammatory response in raw264 7 macrophages by inhibiting nf κb mapk and stats activation
topic xanthatin
RAW 264.7
anti-inflammatory
ROS
NF-κB
MAPK
url https://www.mdpi.com/1420-3049/27/14/4603
work_keys_str_mv AT yuanqiliu xanthatinalleviateslpsinducedinflammatoryresponseinraw2647macrophagesbyinhibitingnfkbmapkandstatsactivation
AT wenyuchen xanthatinalleviateslpsinducedinflammatoryresponseinraw2647macrophagesbyinhibitingnfkbmapkandstatsactivation
AT fangzheng xanthatinalleviateslpsinducedinflammatoryresponseinraw2647macrophagesbyinhibitingnfkbmapkandstatsactivation
AT huananyu xanthatinalleviateslpsinducedinflammatoryresponseinraw2647macrophagesbyinhibitingnfkbmapkandstatsactivation
AT kunwei xanthatinalleviateslpsinducedinflammatoryresponseinraw2647macrophagesbyinhibitingnfkbmapkandstatsactivation