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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, 73 (1). pp. 118-134. ISSN 0022-3573
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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-IB and of phospho-p65, while preventing degradation of IB 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 |
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| Additional Information: | This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Pharmacy and Pharmacology following peer review. The version of record Folashade A Ogunrinade, Stephanie T Guetchueng, Folashade O Katola, Mutalib A Aderogba, Idowu S Akande, Satyajit D Sarker, Olumayokun A Olajide, Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-κB transcription factor and NLRP3 inflammasome activation, Journal of Pharmacy and Pharmacology, Volume 73, Issue 1, January 2021, Pages 118–134 is available online at: https://doi.org/10.1093/jpp/rgaa019 |
| 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: | Oxford University Press |
| Date Deposited: | 29 Sep 2020 09:43 |
| Last Modified: | 11 Jan 2022 15:15 |
| DOI or ID number: | 10.1093/jpp/rgaa019 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/13743 |
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