Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Samuel A. Onasanwo, Ravikanth Velagapudi, Abdelmeneim El-Bakoush, Olumayokun A. Olajide

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)23-36
Number of pages14
JournalMolecular and Cellular Biochemistry
Volume414
Issue number1-2
Early online date2 Feb 2016
DOIs
Publication statusPublished - 1 Mar 2016

Fingerprint

Biflavonoids
Microglia
Antioxidants
Lipopolysaccharides
Nitric Oxide Synthase Type II
RNA Interference
Dinoprostone
Neurons
kolaviron
Garcinia kola
Assays
Reactive Oxygen Species
Anti-Inflammatory Agents
Garcinia
Antioxidant Response Elements
Cytokines
Nuts
Neuroprotective Agents
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases

Cite this

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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.",
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Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism. / Onasanwo, Samuel A.; Velagapudi, Ravikanth; El-Bakoush, Abdelmeneim; Olajide, Olumayokun A.

In: Molecular and Cellular Biochemistry, Vol. 414, No. 1-2, 01.03.2016, p. 23-36.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

AU - Onasanwo, Samuel A.

AU - Velagapudi, Ravikanth

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AU - Olajide, Olumayokun A.

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