scholarly journals Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3β

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yingui Li ◽  
Yijing Zhao ◽  
Xiaoqin Tan ◽  
Jiayan Liu ◽  
Yingkun Zhi ◽  
...  
Keyword(s):  
Western Blotting ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Signal Molecules ◽  
Glycogen Synthase Kinase 3Β ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
The Brain

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.

Microtubule-associated protein 1B phosphorylation by glycogen synthase kinase 3β is induced during PC12 cell differentiation

2001 ◽  
Vol 114 (23) ◽  
pp. 4273-4284 ◽  
Author(s):  
Robert G. Goold ◽  
Phillip R. Gordon-Weeks
Keyword(s):  
Cell Differentiation ◽  
Pc12 Cell ◽  
Glycogen Synthase ◽  
Axon Outgrowth ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Cell Extracts ◽  
Neurite Formation ◽  
Reduced Mobility

In recent studies we have demonstrated that glycogen synthase kinase 3β (GSK3β) and its substrate microtubule-associated protein 1B (MAP1B) regulate the microtubule cytoskeleton during axon outgrowth. To further examine the role GSK3β plays in axon outgrowth we investigated the expression of GSK3β and its activity towards MAP1B during nerve growth factor (NGF)-stimulated PC12 cell differentiation. Levels of GSK3β expression increase relatively little during the course of differentiation. However, the expression of a novel GSK3β isoform characterised by a reduced mobility on SDS gels is induced by NGF. Expression of this isoform and the GSK3β-phosphorylated isoform of MAP1B (MAP1B-P) are induced in parallel in response to NGF. This increase lags behind initial neurite formation and the expression of MAP1B in these cells by about two days and coincides with a period when the majority of cells are extending existing neurites. MAP1B and GSK3β are expressed throughout the PC12 cell but MAP1B-P expression is restricted to the growth cones and neurites. Consistent with these observations, we find that neurite extension is more sensitive to the GSK3 inhibitor Li+ than neurite formation and that this correlates with an inhibition of MAP1B phosphorylation. Additionally, GSK3β from PC12 cells not exposed to NGF can not phosphorylate MAP1B in vitro. However, a soluble factor in differentiated PC12 cell extracts depleted of GSK3β can activate MAP1B phosphorylation from undifferentiated cell extracts otherwise devoid of kinase activity. These experiments provide evidence for an NGF-mediated regulation of MAP1B phosphorylation in growing neurites by the induction of a novel isoform of GSK3β.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

scholarly journals Genetic or pharmacological superoxide-hydrogen peroxide imbalances modulate the in vitro effects of lithium on glycogen synthase kinase-3β

Gene ◽  
2018 ◽  
Vol 655 ◽  
pp. 48-55 ◽  
Author(s):  
Fernanda Barbisan ◽  
Verônica Farina Azzolin ◽  
Gustavo Cardenas Monteiro ◽  
Cibele F. Teixeira ◽  
Moisés Henrique Mastella ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
In Vitro Effects

Detection of Active Fraction of Glycogen Synthase Kinase 3β in Cancer Cells by Nonradioisotopic in vitro Kinase Assay

Oncology ◽  
2006 ◽  
Vol 71 (3-4) ◽  
pp. 297-305 ◽  
Author(s):  
Wei Mai ◽  
Katsuyoshi Miyashita ◽  
Abbas Shakoori ◽  
Bin Zhang ◽  
Zhi Wei Yu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Kinase Assay ◽  
Glycogen Synthase Kinase 3Β ◽  
Active Fraction ◽  
In Vitro Kinase Assay

Anti-Oxidative and Anti-Inflammatory Effects of Lobelia chinensis In Vitro and In Vivo

2015 ◽  
Vol 43 (02) ◽  
pp. 269-287 ◽  
Author(s):  
Kun-Cheng Li ◽  
Yu-Ling Ho ◽  
Guan-Jhong Huang ◽  
Yuan-Shiun Chang
Keyword(s):  
Nitric Oxide ◽  
Folk Medicine ◽  
Ethyl Acetate Fraction ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Factor Α

Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.

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