Flavonoids Isolated from Flowers ofLonicera japonicaThunb. Inhibit Inflammatory Responses in BV2 Microglial Cells by Suppressing TNF-α and IL-β Through PI3K/Akt/NF-kb Signaling Pathways

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

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Shizukaol B, an active sesquiterpene from Chloranthus henryi, attenuates LPS-induced inflammatory responses in BV2 microglial cells

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.01.152 ◽

2017 ◽

Vol 88 ◽

pp. 878-884 ◽

Cited By ~ 5

Author(s):

Li-Long Pan ◽

Peng Xu ◽

Xiao-Ling Luo ◽

Li-Jun Wang ◽

Si-Yu Liu ◽

...

Keyword(s):

Inflammatory Responses ◽

Microglial Cells ◽

Bv2 Microglial Cells

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Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation

Frontiers in Immunology ◽

10.3389/fimmu.2020.600479 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ziqi Fan ◽

Shuai Zhao ◽

Yueli Zhu ◽

Zheyu Li ◽

Zhirong Liu ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Interferon Regulatory Factor ◽

Microglial Cells ◽

Regulatory Factor ◽

Down Regulation ◽

Interferon Regulatory Factor 5 ◽

Bv2 Microglial Cells ◽

Lps Treatment ◽

Pro Inflammatory Cytokines

BackgroundActivated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive.MethodsLipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot.ResultsLPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling.ConclusionsIRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

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Anti-inflammatory Activity of 8-Hydroxydaidzein in LPS-Stimulated BV2 Microglial Cells via Activation of Nrf2-Antioxidant and Attenuation of Akt/NF-κB-Inflammatory Signaling Pathways, as Well As Inhibition of COX-2 Activity

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.8b00437 ◽

2018 ◽

Vol 66 (23) ◽

pp. 5790-5801 ◽

Cited By ~ 17

Author(s):

Pei-Shan Wu ◽

Hsiou-Yu Ding ◽

Jui-Hung Yen ◽

Shu-Fen Chen ◽

Kuan-Han Lee ◽

...

Keyword(s):

Signaling Pathways ◽

Inflammatory Activity ◽

Microglial Cells ◽

Inflammatory Signaling ◽

Cox 2 ◽

Anti Inflammatory ◽

Bv2 Microglial Cells

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Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis

Molecules ◽

10.3390/molecules25204796 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4796

Author(s):

Jiali Chen ◽

Cailin Tang ◽

Yang Zhou ◽

Rongfei Zhang ◽

Shaoxia Ye ◽

...

Keyword(s):

Essential Oil ◽

Mrna Expression ◽

Underlying Mechanism ◽

Treated Group ◽

Microglial Cells ◽

Cinnamomum Camphora ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Bv2 Microglial Cells

Cinnamomum camphora (Linn.) Presl has been widely used in traditional Chinese medicine for a variety of purposes. Our previous study indicated the antibacterial mechanism of the essential oil (EO) from C. camphora leaves; however, its anti-inflammatory activity and the underlying mechanism have not been clearly demonstrated. Thus, the present study investigated its anti-inflammatory property. Our data revealed that EO significantly decreased the release of nitric oxide (NO) and the mRNA expression of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced BV2 microglial cells. EO also attenuated LPS-induced increase in the mRNA expression and secretion of inflammatory cytokines including interleukin-6 (IL-6), IL-18, IL-1β and tumor necrosis factor-α (TNF-α). Furthermore, the metabolic profiles of LPS-induced BV2 microglial cells treated with or without EO were explored. Thirty-nine metabolites were identified with significantly different contents, including 21 upregulated and 18 downregulated ones. Five pathways were enriched by shared differential metabolites. Compared with the control cells, the glucose level was decreased, while the lactate level was increased, in the culture supernatant from LPS-stimulated cells, which were reversed by EO treatment. Moreover, compared to the LPS-treated group, the activities of phosphofructokinase (PFK) and pyruvate kinase (PK) in EO group were decreased. In summary, the current study demonstrated that EO from C. camphora leaves acts as an anti-inflammatory agent, which might be mediated through attenuating the glycolysis capacity of microglial cells.

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Mucuna pruriens (L.) DC. seed extract inhibits lipopolysaccharide-induced inflammatory responses in BV2 microglial cells

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.113518 ◽

2021 ◽

Vol 267 ◽

pp. 113518

Author(s):

Aungkana Rachsee ◽

Natthakarn Chiranthanut ◽

Phraepakaporn Kunnaja ◽

Seewaboon Sireeratawong ◽

Parirat Khonsung ◽

...

Keyword(s):

Inflammatory Responses ◽

Seed Extract ◽

Microglial Cells ◽

Mucuna Pruriens ◽

Bv2 Microglial Cells

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Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

10.21203/rs.2.17199/v2 ◽

2019 ◽

Author(s):

Xin-chun Ye ◽

Qi Hao ◽

Wei-jing Ma ◽

Qiu-chen Zhao ◽

Wei-wei Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Brain Injury ◽

Infarct Volume ◽

Inos Expression ◽

Microglial Cells ◽

Brain Infarct ◽

Tnf Α ◽

Bv2 Microglial Cells ◽

The Brain

Abstract Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Adult male C57BL/6J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test and foot-fault test were evaluated on days 1, 3, 5 and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl’s and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5 and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk and p-Syk expression was increased following the 3-h OGD and 0, 3 and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

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Interferon Regulatory Factor 5 Mediates Lipopolysaccharide Induced Neuroinflammation

10.21203/rs.3.rs-23387/v1 ◽

2020 ◽

Author(s):

Ziqi Fan ◽

Shuai Zhao ◽

Yueli Zhu ◽

Zheyu Li ◽

Zhirong Liu ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Interferon Regulatory Factor ◽

Microglial Cells ◽

Regulatory Factor ◽

Down Regulation ◽

Interferon Regulatory Factor 5 ◽

Bv2 Microglial Cells ◽

Lps Treatment ◽

Pro Inflammatory Cytokines

Abstract Background Activated microglia plays a vital role in neuroinflammation in central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in periphery, the role of which in the CNS remains elusive. Methods Lipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immnunofluorescence and Western blot. Results LPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which returned to basal level at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling. Conclusions IRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

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Isolation of Novel Sesquiterpeniods and Anti-neuroinflammatory Metabolites from Nardostachys jatamansi

Molecules ◽

10.3390/molecules23092367 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2367 ◽

Cited By ~ 6

Author(s):

Chi-Su Yoon ◽

Dong-Cheol Kim ◽

Jin-Soo Park ◽

Kwan-Woo Kim ◽

Youn-Chul Kim ◽

...

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

2D Nmr ◽

Microglial Cells ◽

No Production ◽

Nardostachys Jatamansi ◽

Tnf Α ◽

Factor Α ◽

Oxide Synthase ◽

Bv2 Microglial Cells

Nardostachys jatamansi contains various types of sesquiterpenoids that may play an important role in the potency of plant’s anti-inflammatory effects, depending on their structure. In this study, five new sesquiterpenoids, namely kanshone L (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the rhizomes and roots of Nardostachys jatamansi. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds 3, 4, and 8 were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-12 and tumor necrosis factor-α (TNF-α), in LPS-stimulated BV2 microglial cells. Moreover, these compounds were shown to inhibit the activation of the NF-κB signaling pathway in LPS-stimulated BV2 microglial cells by suppressing the phosphorylation of IκB-α and blocking NF-κB translocation. In conclusion, five new and four known sesquiterpenoids were isolated from Nardostachys jatamansi, and compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.

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