Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation

Kim, Shin Young; Jin, Cheng‐Yun; Kim, Cheol Hong; Yoo, Young Hyun; Choi, Sung Hyun; Kim, Gi‐Young; Yoon, Hyun‐Min; Park, Hwan Tae; Choi, Yung Hyun

doi:10.3892/ijmm.2018.3993

Cited by 60 publications

(59 citation statements)

References 39 publications

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“…It should be noted that the inhibition of the iNOS signaling pathway would also influence the NO production. LPS is an iNOS inducer that increases NO concentrations, through the activation of inducible nuclear factors, including NF‐κβ, so its inhibition would lead to a decrease in NO concentration (Kim et al, 2019), response was also observed in F1–3 kDa of the present study.…”

Section: Resultssupporting

confidence: 73%

Neuroprotective effect from Salvia hispanica peptide fractions on pro‐inflammatory modulation of HMC3 microglial cells

Leo

Campos

2020

J Food Biochem

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Neuroinflammation plays a critical role in the neurodegenerative disease's development, where microglia's act an important role in the mechanisms of response to neuronal damage. In the present research, the neuroprotective effect from Salvia hispanica peptide fractions on the proinflammatory modulation on HMC3 microglial cells was evaluated. From the enzymatic hydrolysis of a protein‐rich fraction from S. hispanica seeds, three peptide fractions (<1, 1–3 and 3–5 kDa) were obtained, from which its neuroprotective and anti‐inflammatory effect was determined on the production of proinflammatory mediators on HMC3 cells. The F1–3 kDa exhibited the greatest protective effect (79.04%), associated with the decrease in ROS cell production (51.3 ± 2.3%). Likewise, F1–3 kDa at 50 µg/ml, presented the highest reduction percentages of NO (33.1 ± 2.30%), TNFα (26.4 ± 1.1%) and IL6 (17.36 ± 1.6%). F1–3 kDa exhibited a neuroprotective effect in HMC3 cells associated with its antioxidant and anti‐inflammatory effect. Practical applications Currently, neurodegenerative diseases represent a global health problem, so the search for bioactive compounds with neuroprotective effect is useful in the prevention and treatment of this group of diseases. Peptide research with an effect on the proinflammatory and prooxidant mediator's reduction presents a potential application in the functional food's development aimed at the treatment of chronic diseases, that have oxidative stress and inflammation as their etiological factor. The present research adds to the scientific evidence of the potential benefits of bioactive peptides obtained from chia seeds. The results correlate with the main health benefits of whole chia seed in humans, such as antioxidant, anti‐inflammatory, hypoglycemic and hypotensive capacity. This relationship is associated with the protein and peptide composition of chia, which increases its added value as food.

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Section: Resultssupporting

confidence: 73%

Neuroprotective effect from Salvia hispanica peptide fractions on pro‐inflammatory modulation of HMC3 microglial cells

Leo

Campos

2020

J Food Biochem

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“…A previous study has found that a plantar injection of CFA could induce mechanical allodynia via microglial activation and induction of pro-inflammatory cytokines in the spinal cord [20,23,26]. In this study, the oral administration of EJE attenuated CFA-induced mechanical allodynia, microglial activation, and the expression of pro-inflammatory cytokines in the spinal cord.…”

Section: Discussionsupporting

confidence: 58%

“…We next investigated the mechanisms underlying the suppressive effect of EJE in LPS-induced microglial activation. Over the course of microglial activation, the MAPK signaling pathway is activated to induce inflammation and the expression of pro-inflammatory cytokines [25,26]. In our data, LPS treatment induced the activation of the MAPK pathways in BV2 microglia.…”

Section: Discussionsupporting

confidence: 52%

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

Park

Kim

2020

Antioxidants

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Microglial activation-mediated neuroinflammation influences the development of inflammatory pain. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of aqueous Erythronium japonicum extract (EJE) in microglia activation-mediated inflammatory pain. EJE was found to suppress lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), ionized calcium-binding adapter molecule 1 (IBA-1), and pro-inflammatory cytokines in BV2 microglial cells. In addition, LPS-induced c-Jun NH2 terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation were inhibited by EJE. Intriguingly, EJE also inhibited p65 phosphorylation by activating extracellular signal-regulated kinase-1/2 (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Furthermore, the effects of EJE treatment, such as HO-1 induction and the reduction of NF-ĸB activation, were reversed by ERK1/2 inhibition. In an inflammatory pain mouse model, Complete Freund’s Adjuvant (CFA)-induced mechanical allodynia and foot swelling were alleviated by the oral administration of EJE. Consistent with in vitro results, EJE increased HO-1, while decreasing CFA-induced COX-2, IBA-1, and pro-inflammatory cytokines in the spinal cord. Among the components of EJE, butanol most heavily suppressed LPS-induced microglial activation and increased HO-1 expression. These findings indicate that EJE can alleviate inflammatory pain by inhibiting p38 and JNK and by suppressing NF-ĸB via ERK/Nrf2/HO-1 signaling.

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“…TLR4/MyD88-dependent signaling recruits IRAK1/TRAF6 complex, leading to TAK1 phosphorylation and subsequently activates NF-κB and MAPKs by phosphorylating IκBα and MAPK signaling pathways [ 39 , 41 ]. TLR4, MyD88, and TRAF6 are weakly expressed by resting cells, but they upregulate following stimulation with LPS [ 42 ]. In our study, although Hp-s1 pretreatment did not affect TLR4 expression, Hp-s1 attenuated LPS-induced the increase in the expression of MyD88 and TRAF6, which contributes to suppressing proinflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

Shih

Tsai

et al. 2020

Marine Drugs

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Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.

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Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation

Cited by 60 publications

References 39 publications

Neuroprotective effect from Salvia hispanica peptide fractions on pro‐inflammatory modulation of HMC3 microglial cells

Neuroprotective effect from Salvia hispanica peptide fractions on pro‐inflammatory modulation of HMC3 microglial cells

Erythronium japonicum Alleviates Inflammatory Pain by Inhibiting MAPK Activation and by Suppressing NF-κB Activation via ERK/Nrf2/HO-1 Signaling Pathway

Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

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