title: Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism.
abstract: Kolaviron is a mixture of biflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-κB and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assays and reporter assays. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the pro-inflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IκB/NF-κB signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/antioxidant response element pathway. RNAi experiments revealed that Nrf2 is needed for the anti-inflammatory effects of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders.
authors.affiliation: Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Onasanwo
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Velagapudi
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.
authors.forename: Abdelmeneim
authors.initials: A
authors.lastname: El-Bakoush
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK. o.a.olajide@hud.ac.uk.
authors.forename: Olumayokun A
authors.initials: OA
authors.lastname: Olajide
mesh_terms: D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020868:Gene Silencing; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
chemical_list: D051546:Cyclooxygenase 2; D015232:Dinoprostone; D005419:Flavonoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C495636:Nfe2l2 protein, mouse; C045492:kolaviron
keywords: Kolaviron; Microglia; Neuroinflammation; Neuroprotective; Nrf2 signalling pathway
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