TAZ ameliorates the microglia-mediated inflammatory response via the Nrf2-ROS-NF-κB pathway

Huang, Ji-Cheng; Yue, Zhan‐Peng; Yu, Hai-Fan; Yang, Zhan-Qing; Wang, Yusi; Guo, Bin

doi:10.1016/j.omtn.2022.03.025

Cited by 36 publications

(22 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under the normal state, NF‐κB normally combines with IκB protein complex to keep inactive in the cytoplasm. However, the activation of IKKα/β induces IκBα phosphorylation and degradation, which allows the liberation of NF‐κB p65 subunit and translocation to nuclear to release the pro‐inflammatory cytokines in microglia 18 . A growing body of research has suggested NF‐κB signaling as a potential therapeutic target in attenuating inflammation and brain damage in ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

AZD1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia‐mediated neuroinflammation and ischemic brain injury

Lan,

Qu,

Liang

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

AimsExcessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio‐sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown.MethodsReal‐time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme‐linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5‐Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF‐κB signaling pathway was explored through immunofluorescence staining, western blot, co‐immunoprecipitation and proximity ligation assay.ResultsThe level of pro‐inflammation cytokines and activation of NF‐κB signaling pathway was suppressed by AZD1390 in vitro and in vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF‐κB (NEMO) in an ATM‐dependent and ATM‐independent way respectively, which reduced the activation of the NF‐κB pathway.ConclusionAZD1390 suppressed NF‐κB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

AZD1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia‐mediated neuroinflammation and ischemic brain injury

Lan,

Qu,

Liang

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…The additive effects of CA and GK contribute to enhancing the effects of the ingredient mixture on Nrf2 activation (Liu et al, 2020;Matthews et al, 2019). Third, the mixture interferes with the crosstalk between NF-κB and Nrf2 (Huang et al, 2022;Wardyn et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A mixture of extracts from natural ingredients reduces the neurotoxic polarization of microglia via modulating NF‐κB/NF‐E2‐related factor 2 activation

Gui,

Ni,

Mizutani

et al. 2024

Food Science & Nutrition

View full text Add to dashboard Cite

Neurotoxic microglia‐provoked neuroinflammation is implicated in cognitive decline in Alzheimer's disease (AD). Supplementation with Ginkgo biloba, phosphatidylserine, Curcuma longa, and propolis is reported to improve the cognitive functions of elderly people; however, the underlying mechanisms of this combination of natural ingredients are unknown. We investigated the effects of a mixture of extracts from propolis, Coffea arabica, Gotu kola, phosphatidylserine, Ginkgo biloba, and Curcuma longa (mixture) on microglia polarization after exposure to amyloid β1‐42 (Aβ1‐42, 1 μM) and lipopolysaccharide from Porphyromonas gingivalis (PgLPS, 1 μg/mL), using MG6 and BV2 microglial cells. Exposure to Aβ1‐42 and PgLPS (AL) raised the mRNA expression of IL‐1β, TNF‐α, and IL‐6, nuclear translocation of p65 NF‐κB in MG6 cells and BV2 cells, and mitochondrial reactive oxygen species (ROS) production in MG6 cells. The mixture dramatically suppressed the mRNA expression of IL‐1β, TNF‐α, and IL‐6, but significantly promoted that of IL‐10, TGFβ1, and BDNF in AL‐exposed MG6 and BV2 cells. Furthermore, the mixture significantly suppressed the nuclear translocation of p65 NF‐κB but significantly promoted that of NF‐E2‐related factor 2 (Nrf2) in AL‐exposed MG6 and BV2 cells. Furthermore, the mixture significantly ameliorated mitochondrial ROS production but increased mitochondrial membrane potential in MG6 cells. These observations strongly suggest that the mixture demotes the neuropathic polarization of microglia by modulating NF‐κB/Nrf2 activation and improving mitochondrial functions. This study supplies the potential mechanisms of the efficacy of a combination of natural ingredients that can be applied in the prevention of cognitive decline in AD and aging by targeting microglia‐mediated neuroinflammation.

show abstract

“…Several studies have confirmed that drugs can play an anti-hepatic fibrosis role by regulating Nrf2/ARE pathway. For example, Baicalein can regulate Nrf2/HO-1 and Bcl-2/Bax pathways to treat CCl 4 -induced liver fibrosis [ 48 ]; Quercetin ethyl acetate inhibits liver fibrosis in rats via decreasing the expression of α-SMA and TIMP1 depended on Nrf2 protein [ 49 ]; Ursolic acid can regulate Nrf2/ARE pathway, which can significantly prevent CCl 4 induced hepatotoxicity and fibrosis [ 50 ]. Therefore, further study of the Nrf2/ARE pathway will explain the new mechanism of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

Wei

Gao

Wang

et al. 2023

J Animal Sci Biotechnol

View full text Add to dashboard Cite

Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments. Mori fructus aqueous extracts (MFAEs) have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present. Purpose To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism. Methods and results Mice were divided into 5 groups (n = 8) for acute (groups: control, 0.3% CCl4, bifendate (BD), 100 and 200 mg/kg MFAEs, 7 d) and chronic (groups: control, 10% CCl4, BD, 100 and 200 mg/kg MFAEs, 4 weeks) liver injury study. Each mouse was injected intraperitoneally with 10 µL/g corn oil containing CCl4 expect the control group. HepG2 cells were used in vitro study. Eighteen communal components were identified by UPLC-LTQ-Orbitrap-MS. We utilized a mouse model for acute and chronic liver injury using CCl4 and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver. MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1 (Nrf2/HO-1) pathway and promoted the synthesis of the antioxidants glutathione (GSH), superoxidedismutase (SOD) and glutathione peroxidase (GSH-Px) that resulted in reduced levels of CCl4-induced oxidative stress molecules including reactive oxygen species. These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thus reducing the occurrence of liver fibrosis. Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling. These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor. Conclusion MFAEs inhibited oxidative stress, ferroptosis and inflammation of the liver by activating Nrf2 signal pathway and provided a significant protective effect against CCl4-induced liver fibrosis. Graphical Abstract

show abstract

TAZ ameliorates the microglia-mediated inflammatory response via the Nrf2-ROS-NF-κB pathway

Cited by 36 publications

References 44 publications

AZD1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia‐mediated neuroinflammation and ischemic brain injury

AZD1390, an ataxia telangiectasia mutated inhibitor, attenuates microglia‐mediated neuroinflammation and ischemic brain injury

A mixture of extracts from natural ingredients reduces the neurotoxic polarization of microglia via modulating NF‐κB/NF‐E2‐related factor 2 activation

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

Contact Info

Product

Resources

About