Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β
Joint Authors
Du, Qun
Li, Yingui
Zhao, Yijing
Tan, Xiaoqin
Liu, Jiayan
Zhi, Yingkun
Yi, Lang
Bai, Shasha
Li, Qing X.
Dong, Yan
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-10-28
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Isoorientin has anti-inflammatory effects; however, the mechanism remains unclear.
We previously found isoorientin is an inhibitor of glycogen synthase kinase 3β (GSK3β) in vitro.
Overactivation of GSK3β is associated with inflammatory responses.
GSK3β is inactivated by phosphorylation at Ser9 (i.e., p-GSK3β).
Lithium chloride (LiCl) inhibits GSK3β and also increases p-GSK3β (Ser9).
The present study investigated the anti-inflammatory effect and mechanism of isoorientin via GSK3β regulation in lipopolysaccharide- (LPS-) induced RAW264.7 murine macrophage-like cells and endotoxemia mice.
LiCl was used as a control.
While AKT phosphorylates GSK3β, MK-2206, a selective AKT inhibitor, was used to activate GSK3β via AKT inhibition (i.e., not phosphorylate GSK3β at Ser9).
The proinflammatory cytokines TNF-α, IL-6, and IL-1β were detected by ELISA or quantitative real-time PCR, while COX-2 by Western blotting.
The p-GSK3β and GSK3β downstream signal molecules, including NF-κB, ERK, Nrf2, and HO-1, as well as the tight junction proteins ZO-1 and occludin were measured by Western blotting.
The results showed that isoorientin decreased the production of TNF-α, IL-6, and IL-1β and increased the expression of p-GSK3β in vitro and in vivo, similar to LiCl.
Coadministration of isoorientin and LiCl showed antagonistic effects.
Isoorientin decreased the expression of COX-2, inhibited the activation of ERK and NF-κB, and increased the activation of Nrf2/HO-1 in LPS-induced RAW264.7 cells.
Isoorientin increased the expressions of occludin and ZO-1 in the brain of endotoxemia mice.
In summary, isoorientin can inhibit GSK3β by increasing p-GSK3β and regulate the downstream signal molecules to inhibit inflammation and protect the integrity of the blood-brain barrier and the homeostasis in the brain.
American Psychological Association (APA)
Li, Yingui& Zhao, Yijing& Tan, Xiaoqin& Liu, Jiayan& Zhi, Yingkun& Yi, Lang…[et al.]. 2020. Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1192122
Modern Language Association (MLA)
Li, Yingui…[et al.]. Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β. Mediators of Inflammation No. 2020 (2020), pp.1-10.
https://search.emarefa.net/detail/BIM-1192122
American Medical Association (AMA)
Li, Yingui& Zhao, Yijing& Tan, Xiaoqin& Liu, Jiayan& Zhi, Yingkun& Yi, Lang…[et al.]. Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-10.
https://search.emarefa.net/detail/BIM-1192122
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192122