Anti-inflammatory mechanism of lonchocarpine in LPS- or poly(I:C)-induced neuroinflammation

In response to foreign or endogenous stimuli, both microglia and astrocytes adopt an activated phenotype that promotes the release of pro-inflammatory mediators. This inflammatory mechanism, known as neuroinflammation, is essential in the defense against foreign invasion and in normal tissue repair; nevertheless, when constantly activated, this process can become detrimental through the release of neurotoxic factors that amplify underlying disease. In consequence, this study presents the anti-inflammatory and immunomodulatory properties of o-orsellinaldehyde, a natural compound found by an in silico approach in the Grifola frondosa mushroom, in astrocytes and microglia cells. For this purpose, primary microglia and astrocytes were isolated from mice brain and cultured in vitro. Subsequently, cells were exposed to LPS in the absence or presence of increasing concentrations of this natural compound. Specifically, the results shown that o-orsellinaldehyde strongly inhibits the LPS-induced inflammatory response in astrocytes and microglia by decreasing nitrite formation and downregulating iNOS and HO-1 expression. Furthermore, in microglia cells o-orsellinaldehyde inhibits NF-κB activation; and potently counteracts LPS-mediated p38 kinase and JNK phosphorylation (MAPK). In this regard, o-orsellinaldehyde treatment also induces a significant cell immunomodulation by repolarizing microglia toward the M2 anti-inflammatory phenotype. Altogether, these results could partially explain the reported beneficial effects of G. frondosa extracts on inflammatory conditions.

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Predicting the Anti-Inflammatory Mechanism of Polygonum perfoliatum L based on Network Pharmacology

IOP Conference Series Earth and Environmental Science ◽

10.1088/1755-1315/632/5/052012 ◽

2021 ◽

Vol 632 ◽

pp. 052012

Author(s):

Mei Zhang ◽

Xulong Huang ◽

Feng Xu ◽

Ping Qin ◽

Qin Din ◽

...

Keyword(s):

Network Pharmacology ◽

Inflammatory Mechanism ◽

Polygonum Perfoliatum ◽

Anti Inflammatory

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High-throughput RNA sequencing reveals the anti-inflammatory mechanism of baicalin on Propionibacterium acnes-induced acne in rabbits

Journal of Traditional Chinese Medical Sciences ◽

10.1016/j.jtcms.2019.09.001 ◽

2019 ◽

Vol 6 (3) ◽

pp. 201-210

Author(s):

Xingzhe Yang ◽

Guangrui Huang ◽

Leiming You ◽

Honghao Sheng ◽

Yuxiu Sun ◽

...

Keyword(s):

Rna Sequencing ◽

High Throughput ◽

Propionibacterium Acnes ◽

Inflammatory Mechanism ◽

Anti Inflammatory

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Anti-inflammatory Effects ofScoparia dulcisL. and Betulinic Acid

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009329 ◽

2011 ◽

Vol 39 (05) ◽

pp. 943-956 ◽

Cited By ~ 38

Author(s):

Jen-Chieh Tsai ◽

Wen-Huang Peng ◽

Tai-Hui Chiu ◽

Shang-Chih Lai ◽

Chao-Ying Lee

Keyword(s):

Betulinic Acid ◽

High Performance ◽

Ethanol Extract ◽

Paw Edema ◽

Scoparia Dulcis ◽

Inflammatory Mechanism ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Analytical Result

The aims of this study intended to investigate the anti-inflammatory activity of the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and malondialdehyde (MDA) in the edema paw tissue and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRd) in the liver. The betulinic acid content in SDE was detected by high performance liquid chromatography (HPLC). In the anti-inflammatory model, the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40 mg/kg) reduced the paw edema at 3, 4 and 5 h after λ-carrageenan administration. Moreover, SDE and betulinic acid affected the levels of COX-2, NO, TNF-α and IL1-β in the λ-carrageenan-induced edema paws. The activities of SOD, GPx and GRd in the liver tissue were increased and the MDA levels in the edema paws were decreased. It is suggested that SDE and betulinic acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms appear to be related to the reduction of the levels of COX-2, NO, TNF-α and IL1-β in inflamed tissues, as well as the inhibition of MDA level via increasing the activities of SOD, GPx and GRd. The analytical result showed that the content of betulinic acid in SDE was 6.25 mg/g extract.

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Immunomodulatory role of paliperidone in the poly(I:C) model of schizophrenia

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.541 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s220-s221

Author(s):

K. MacDowell ◽

E. Munarriz-Cuezva ◽

D. Martín-Hernández ◽

A. Sayd ◽

B. García-Bueno ◽

...

Keyword(s):

Antioxidant Enzymes ◽

Inflammatory Responses ◽

Poly I:C ◽

Mrna Levels ◽

Behavioral Test ◽

Inflammatory Pathways ◽

Anti Inflammatory ◽

Cellular Markers ◽

Endogenous Antioxidant

IntroductionAlterations on the innate inflammatory response may underlie the pathophysiology of psychiatric diseases, but the mechanisms implicated remain elusive. Current antipsychotics modulate pro/anti-inflammatory pathways, but the specific mechanisms involved remain elusive. One attractive possibility is the regulation of the intracellular signalling pathways of the innate immune receptors Toll-like 3 (TLR3), which triggers antiviral and inflammatory responses.AimsTo elucidate the regulatory role of paliperidone on maternal immune activation (MIA) induced alterations on TLR3 pathway and on the two emerging endogenous antiinflammatory/antioxidant mechanisms NRF2/antioxidant enzymes pathway and the cytokine milieu regulating M1/M2 polarization in microglia.MethodsPregnant mice were treated with the synthetic Toll-like Receptor 3 (TLR3) agonist Poly(I:C) in gestational day 9 and chronically treated with paliperidone (0,05 mg/kg i.p.) in adult offspring. Animals were sacrificed one day after treatment and behavioral test. Inflammation oxidative stress-related mediators were analysed at mRNA and protein level in prefrontal cortex samples. In addition, behavioral test t-maze was conducted.ResultsPaliperidone prevented TLR3 pathway activation and the subsequent MIA-induced neuroinflammatory response. Also, paliperidone induced an increment in the activity and protein expression of nuclear NRF2, as well as increased mRNA levels of the antioxidant enzymes HO1, SOD and catalase in the MIA model. Otherwise, paliperidone increases the antiinflammatory cytokines levels TGFβ and IL-10 in favour of a M2 microglia profile and increased the levels of the M2 cellular markers ArgI and FOLR2.ConclusionsThe modulation of neuroinflammation and enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells

Cells ◽

10.3390/cells9030577 ◽

2020 ◽

Vol 9 (3) ◽

pp. 577

Author(s):

Vijayasree V. Giridharan ◽

Giselli Scaini ◽

Gabriela D. Colpo ◽

Tejaswini Doifode ◽

Omar F. Pinjari ◽

...

Keyword(s):

Cell Cultures ◽

Nlrp3 Inflammasome ◽

Antipsychotic Drugs ◽

Poly I:C ◽

Tnf Α ◽

Cytokine Levels ◽

Primary Microglial Cell ◽

Anti Inflammatory ◽

The Brain ◽

Nlrp3 Expression

Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have suggested the presence of neuroinflammation in schizophrenia. In the present study, the effect of antipsychotic drugs, including clozapine, risperidone, and haloperidol (10, 20 and 20 μM, respectively), on the production of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-18, INF-γ, and TNF-α was investigated in the unstimulated and polyriboinosinic-polyribocytidilic acid [poly (I:C)]-stimulated primary microglial cell cultures. In the unstimulated cultures, clozapine, risperidone, and haloperidol did not influence the cytokine levels. Nevertheless, in cell cultures under strong inflammatory activation by poly (I:C), clozapine reduced the levels of IL-1α, IL-1β, IL-2, and IL-17. Risperidone and haloperidol both reduced the levels of IL-1α, IL-1β, IL-2, and IL-17, and increased the levels of IL-6, IL-10, INF-γ, and TNF-α. Based on the results that were obtained with the antipsychotic drugs and observing that clozapine presented with a more significant anti-inflammatory effect, clozapine was selected for the subsequent experiments. We compared the profile of cytokine suppression obtained with the use of NLRP3 inflammasome inhibitor, CRID3 to that obtained with clozapine, to test our hypothesis that clozapine inhibits the NLRP3 inflammasome. Clozapine and CRID3 both reduced the IL-1α, IL-1β, IL-2, and IL-17 levels. Clozapine reduced the level of poly (I:C)-activated NLRP3 expression by 57%, which was higher than the reduction thay was seen with CRID3 treatment (45%). These results suggest that clozapine might exhibit anti-inflammatory effects by inhibiting NLRP3 inflammasome and this activity is not typical with the use of other antipsychotic drugs under the conditions of strong microglial activation.

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