<i>Zanthoxylum zanthoxyloides</i> inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-κB transcription factor and NLRP3 inflammasome activation

Ogunrinade, Folashade; Guetchueng, Stéphanie Tamdem; Katola, Folashade O; Aderogba, M.A.; Akande, IS; Sarker, Satyajit D.; Olajide, Olumayokun A.

doi:10.1093/jpp/rgaa019

Cited by 11 publications

(10 citation statements)

References 45 publications

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“…There have been suggestions in scienti c literature that malaria hemozoin activates NLRP3 in ammasome/caspase-1 pathway to release IL-1β (Dostert et al 2009;Shio et al 2009;Velagapudi et al 2019;Ogunrinade et al 2021). In this study, we have demonstrated signi cant inhibition of hemozoininduced NLRP3 protein expression by all plants investigated.…”

Section: Discussionsupporting

confidence: 50%

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Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria

Olajide¹,

Iwuanyanwu²

2021

Preprint

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This study aimed to investigate some antimalarial plants for effects on neuroinflammation. Freeze-dried infusions of the plants were investigated for effects on hemozoin-induced neuroinflammation in BV-2 microglia and levels of inflammatory mediators measured. Alstonia boonei (stem bark), Anacardium occidentale (stem bark), Azadiractha indica (leaves), Enantia chlorantha (stem bark), Khaya senegalensis (stem bark), Mangifera indica (stem bark), and Nauclea latifolia (stem bark) produced significant (p<0.05) reduction in TNFα, IL-6, IL-1β, MCP-1, RANTES and iNOS/NO production in BV-2 microglia stimulated with a synthetic hemozoin (400 µg/mL). Further experiments showed that pre-treatment with 50 µg/mL of A. boonei, A. indica, A. occidentale, E. chlorantha and M. indica prior to hemozoin stimulation resulted in inhibition of NF-κB activation by >40%, while E. chlorantha, K. senegalensis and N. latifolia produced weak activities. Pretreatment with A. indica (50 µg/mL) produced the highest inhibition (58.6%) of hemozoin-induced increased NLRP3 protein expression, while A. occidentale (50 µg/mL), M. indica (50 µg/mL) and A. boonei (50 µg/mL) reduced expression by 54.1%, 49.2% and 47.1%, respectively. Hemozoin-induced increased caspase-1 activity was reduced by A. boonei, A. occidentale, A. indica, E. chlorantha, and M. indica. These results suggest that A. boonei, A. occidentale, A. indica and M. indica produced strong inhibition of hemozoin-induced neuroinflammation through mechanisms involving NFκB and NLRP3 inflammasome activation, while moderate activities were produced by E. chlorantha, K. senegalensis and N. latifolia. The outcome of the study provides pharmacological evidence for the potential benefits of the plants as herbal treatments of cerebral malaria symptoms.

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Section: Discussionsupporting

confidence: 50%

“…Recently, we reported that an extract of Zanthoxylum zanthoxyloides attenuated neuroin ammation induced with synthetic hemozoin in BV-2 microglia (Ogunrinade et al 2021). These reports are encouraging developments, and suggest that further pharmacological evaluation of plants used in TAM for treating malaria and/or CM is warranted.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria

Olajide¹,

Iwuanyanwu²

2021

Preprint

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“…As a downstream factor of TLR4/MyD88/IRAK, NF-κB also shows a pivotal role in inflammation meditated by microglia. Blockade of NF-κB transcription in the microglial nucleus leads to the downregulation of NO, PGE2, and related proinflammatory cytokines [37][38][39]. In the cytoplasm, phosphorylation of IκBα results in its further ubiquitination and degradation, and consequently, NF-κB dimers are released and translocated to the nucleus to activate the expression of target genes [40].…”

Section: Discussionmentioning

confidence: 99%

Baicalin Mitigates the Neuroinflammation through the TLR4/MyD88/NF-κB and MAPK Pathways in LPS-Stimulated BV-2 Microglia

Wang

Chen

et al. 2022

BioMed Research International

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Baicalin (BA) is a major flavone from Scutellaria baicalensis Georgi and has showed significant curative effects in Parkinson’s and Alzheimer’s diseases. In the present study, we investigated the effects of BA on antineuroinflammation and related signaling cascade in lipopolysaccharide- (LPS-) induced BV-2 microglial model. The results showed that BA significantly attenuated inflammatory mediators (NO, iNOS, IL-1β, COX-2, and PGE2) and suppressed the expression of miR-155. More crucially, BA could regulate the expression of related proteins in Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor κB (NF-κB) pathway and suppress the phosphorylation of mitogen-activated protein kinase (MAPK) family. In addition, molecular docking analysis indicated that BA binds to the amino acids Lie 63 and Tyr 65 of TLR4 by π - σ and π - π T-shaped interaction. Thus, BA suppressed the LPS-stimulated neuroinflammation in BV-2 microglia by blocking the TLR4-mediated signal transduction through TLR4/MyD88/NF-κB and MAPK pathways and inhibiting the miR-155 expression. Our findings demonstrated that BA could be a valuable therapeutic for the treatment of neuroinflammation and neurodegenerative diseases.

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“…Skimmianine {4, 7, 8-Trimethoxyfuro [2, 3-b] quinoline} ( Figure 1 ) is the most abundant furoquinoline alkaloid found in the Zanthoxylum genus, and also in other genera of the family Rutaceae [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

et al. 2023

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Skimmianine is a furoquinoline alkaloid which is found in the Zanthoxylum genus and also in other plants of the Rutaceae family. This study evaluated the effects of skimmianine on the production of pro-inflammatory mediators in LPS-activated BV-2 microglia. Cultured BV-2 cells were treated with skimmianine (10, 20 and 30 μM), followed by stimulation with LPS (100 ng/mL). Levels of TNFα and IL-6 in cell supernatants were measured using ELISA, while NO and PGE2 levels were evaluated with Griess assay and EIA, respectively. Western blotting was used to determine the protein expression of iNOS, COX-2, phospho-p65 and phospho-IκBα. Results showed that Skimmianine reduced LPS-induced elevated the secretion of TNFα, IL-6, NO, and PGE2, as well as the increased protein expression of iNOS and COX-2. Experiments to elucidate the mechanisms of the anti-neuroinflammatory activity of skimmianine revealed the significant inhibition of LPS-induced increased NF-κB-mediated luciferase activity. Pre-treatment with skimmianine also reduced LPS-induced the increased phosphorylation of NF-κB/p65 and IκBα proteins. Furthermore, skimmianine interfered with the binding capacity of NF-κB to consensus sites. Skimmianine pre-treatment protected HT-22 cells from toxicity induced by microglia-conditioned media, as well as increasing MAP-2 expression. The results of this study suggest that skimmianine inhibits neuroinflammation in LPS-activated microglia by targeting the NF-κB activation pathway. Skimmianine also produced neuroprotection against neurotoxicity induced by microglia-conditioned media.

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Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-κB transcription factor and NLRP3 inflammasome activation

Cited by 11 publications

References 45 publications

Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria

Inhibition of hemozoin-induced neuroinflammation by medicinal plants used for the treatment of malaria in Southwest Nigeria: implications for cerebral malaria

Baicalin Mitigates the Neuroinflammation through the TLR4/MyD88/NF-κB and MAPK Pathways in LPS-Stimulated BV-2 Microglia

Neuroprotection by Skimmianine in Lipopolysaccharide-Activated BV-2 Microglia

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