Impact of environmental toxicants on p38- and ERK-MAPK signaling pathways in the central nervous system

Abstract Background Patchouli alcohol (PA) is a tricyclic sesquiterpene extracted from Pogostemonis Herba, which is a traditional Chinese medicine used for therapy of inflammatory diseases. Recent studies have shown that PA has various pharmacological activities, including anti-bacterial and anti-viral effects. Methods In this study, the anti-influenza virus (IAV) activities and mechanisms were investigated both in vitro and in vivo. The inhibitory effects of PA against IAV in vitro were evaluated by plaque assay and immunofluorescence assay. The neuraminidase inhibition assay, hemagglutination inhibition (HI) assay, and western blot assay were used to explore the anti-viral mechanisms. The anti-IAV activities in vivo were determined by mice pneumonia model and HE staining. Results The results showed that PA significantly inhibited different IAV strains multiplication in vitro, and may block IAV infection through inactivating virus particles directly and interfering with some early stages after virus adsorption. Cellular PI3K/Akt and ERK/MAPK signaling pathways may be involved in the anti-IAV actions of PA. Intranasal administration of PA markedly improved mice survival and attenuated pneumonia symptoms in IAV infected mice, comparable to the effects of Oseltamivir. Conclusions Therefore, Patchouli alcohol has the potential to be developed into a novel anti-IAV agent in the future.

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Effect of Luteolin and Apigenin on the Production of Il-31 and Il-33 in Lipopolysaccharides-Activated Microglia Cells and Their Mechanism of Action

Nutrients ◽

10.3390/nu12030811 ◽

2020 ◽

Vol 12 (3) ◽

pp. 811 ◽

Cited By ~ 1

Author(s):

Denis Nchang Che ◽

Byoung Ok Cho ◽

Ji-su Kim ◽

Jae Young Shin ◽

Hyun Ju Kang ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurodegenerative Diseases ◽

Signaling Pathways ◽

Nuclear Translocation ◽

Mapk Pathway ◽

Microglial Cells ◽

Stat3 Signaling ◽

Protein Expressions ◽

The Central Nervous System

Microglia cells are resident cells of the central nervous system (CNS) charged with modulating inflammation in the CNS. Overstimulation of microglia cells continuously releases inflammatory mediators that contribute to neurodegenerative diseases. Apigenin and Luteolin are flavonoids with reported anti-inflammatory activities. However, their effects on IL-31 and IL-33 production in microglial cells are unknown. Here, we investigated the effects of apigenin and luteolin on the production of IL-31 and IL-33 by microglia cells. SIM-A9 microglial cells were pre-treated with apigenin or luteolin and stimulated with lipopolysaccharides to evaluate the production of IL-31 and IL-33. The study revealed that apigenin and luteolin inhibited the production of IL-31 and IL-33 at the gene and protein expressions and the secretion levels. Using potent inhibitors of MAPK, NF-κB, and STAT3 signaling pathways, we demonstrated that apigenin and luteolin’s suppression of ERK and JNK contributed to the inhibition of IL-31 and IL-33 in the MAPK pathway. Luteolin’s suppression of NF-κB and STAT3 also contributed to the inhibition of IL-31 and IL-33. Further analysis revealed that both compounds prevented nuclear translocation of activated NF-κB and STAT3, an act that subsequently prevented their DNA binding activities. Collectively, the study suggested that apigenin and luteolin’s regulation of signaling pathways contributed to the inhibition of IL-31 and IL-33, thus suggesting its importance for the improvement of neurodegenerative diseases involving these two cytokines.

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Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2/9 by Blocking NF-κB and ERK/MAPK Signaling Pathways

PLoS ONE ◽

10.1371/journal.pone.0123781 ◽

2015 ◽

Vol 10 (4) ◽

pp. e0123781 ◽

Cited By ~ 42

Author(s):

Yuping Liu ◽

Pingting Zhu ◽

Yingyu Wang ◽

Zhonghong Wei ◽

Li Tao ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Mapk Signaling ◽

Diallyl Trisulfide ◽

Erk Mapk ◽

Mapk Signaling Pathways

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Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection

Journal of Virology ◽

10.1128/jvi.02433-08 ◽

2009 ◽

Vol 83 (10) ◽

pp. 5035-5045 ◽

Cited By ~ 11

Author(s):

J. David Beckham ◽

Kathryn Tuttle ◽

Kenneth L. Tyler

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Signaling Pathways ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Bmp Signaling ◽

Downstream Signaling ◽

Morphogenetic Protein ◽

The Central Nervous System

ABSTRACT Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.

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