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Inhibition of neuroinflammation in LPS-activated microglia by cryptolepine

Olajide, Olumayokun A, Bhatia, Harsharan S., de Oliveira, Antonio C Pinheiro, Wright, Colin W and Fiebich, B.L. (2013) Inhibition of neuroinflammation in LPS-activated microglia by cryptolepine. Evidence-Based Complementary and Alternative Medicine, 2013. pp. 1-10. ISSN 1741-427X

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Cryptolepine, an indoloquinoline alkaloid in Cryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2 synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB) and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM) did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Olumayokun Olajide
Date Deposited: 20 Mar 2013 12:25
Last Modified: 28 Aug 2021 11:26


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