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

Ogunrinade, FA, Guetchueng, S, Katola, FO, Aderogba, MA, Akande, IS, Sarker, SD and Olajde, OA Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-B transcription factor and NLRP3 inflammasome activation. Journal of Pharmacy and Pharmacology. ISSN 0022-3573 (Accepted)

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Abstract

Objectives: The effects of a root extract of Zanthoxylum zanthoxyloides on neuroinflammation in BV-2 microglia stimulated with LPS and hemozoin were investigated.
Methods: ELISA, enzyme immunoassay and Griess assay were used to evaluate levels of cytokines, PGE2 and NO in culture supernatants, respectively. Microgliamediated neurotoxicity was evaluated using a BV-2 microglia-HT-22 neuron transwell co-culture.
Key findings: Treatment with Z. zanthoxyloides caused reduced elevated levels of TNF, IL-6, IL-1, NO, and PGE2, while increasing the levels of IL-10. In addition, there were reduced levels of iNOS and COX-2 proteins. This was accompanied by a prevention of microglia-mediated damage to HT-22 mouse hippocampal neurons. Z. zanthoxyloides reduced elevated levels phospho-IB and of phospho-p65, while preventing degradation of IB protein and DNA binding of p65. Further mechanistic studies revealed that Z. zanthoxyloides reduced the levels of pro-IL-1 and IL-1 in hemozoin-activated BV-2 microglia. This was accompanied by a reduction in caspase-1 activity and NLRP3 protein expression. Bioassay-guided fractionation resulted in the isolation of skimmianine as an anti-inflammatory compound in Z. zanthoxyloides.
Conclusion: This is the first report showing inhibition of neuroinflammation in LPSand hemozoin-activated BV-2 microglia by the root extract of Z. zanthoxyloides by targeting the activation of both NF-B and NLRP3 inflammasome.

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology and Pharmaceutical Sciences, 1116 Medical Physiology
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RV Botanic, Thomsonian, and eclectic medicine
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Date Deposited: 29 Sep 2020 09:43
Last Modified: 29 Sep 2020 09:45
URI: https://researchonline.ljmu.ac.uk/id/eprint/13743

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