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

Onasanwo, Samuel Adetunji; Velagapudi, Ravikanth; El‐Bakoush, Abdelmeneim; Olajide, Olumayokun A.

doi:10.1007/s11010-016-2655-8

Cited by 67 publications

(43 citation statements)

References 33 publications

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“…Several flavonoids have been shown to exert NF‐κB inhibitory activity in neuroinflammation. Similar results have been reported for flavonoids such as tiliroside, kolaviron (a biflavonoid in Garcinia kola ), genistein, luteolin, and apigenin (Ha et al, ; Jang, Dilger, & Johnson, ; Onasanwo, Velagapudi, El‐Bakoush, & Olajide, ; Park et al, ; Velagapudi, Aderogba, & Olajide, ).…”

Section: Resultssupporting

confidence: 77%

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Agathisflavone isolated from Anacardium occidentale suppresses SIRT1‐mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe‐transfected SH‐SY5Y cells

Velagapudi

Ajileye

Okorji

et al. 2018

Phytotherapy Research

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Agathisflavone is a bioactive compound in Anacardium occidentale. In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH-SY5Y cells. Experiments in lipopolysaccharide (LPS)-activated BV2 microglia showed that pretreatment with agathisflavone (5-20 μM) produced significant reduction in the release of tumour necrosis factor-α, interleukin-6, interleukin-1β, NO, and PGE from the cells. Immunoblotting experiments also revealed that agathisflavone reduced levels of iNOS and COX-2 protein. Further studies revealed that agathisflavone reduced neuroinflammation by targeting critical steps in NF-κB signalling in BV2 microglia. Treatment of SH-SY5Y cells with conditioned medium from LPS-activated BV2 microglia produced a significant reduction in neuronal viability. However, conditioned medium from BV2 cells that were stimulated with LPS in the presence of agathisflavone did not induce neurotoxicity. Agathisflavone also produced neuroprotection in APPSwe plasmid-transfected SH-SY5Y neurons. The compound further attenuated LPS-induced and APPSwe plasmid-induced reduction in SIRT1 in BV2 microglia and SH-SY5Y, respectively. In the presence of EX527, agathisflavone lost its anti-inflammatory and neuroprotective activities. Our results suggest that agathisflavone inhibits neuroinflammation in BV2 microglia by targeting NF-κB signalling pathway. The compound also reduces neurotoxicity through mechanisms that are possibly linked to SIRT1 in the microglia and neurons.

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Section: Resultssupporting

confidence: 77%

“…The results also confirm that the compound prevents neuroinflammation by targeting NF-κB. genistein, luteolin, and apigenin (Ha et al, 2008;Jang, Dilger, & Johnson, 2010;Onasanwo, Velagapudi, El-Bakoush, & Olajide, 2016;Park et al, 2007;Velagapudi, Aderogba, & Olajide, 2014).…”

Section: Agathisflavone Targets Iκb/nf-κb Activation To Inhibit Neusupporting

confidence: 68%

Agathisflavone isolated from Anacardium occidentale suppresses SIRT1‐mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe‐transfected SH‐SY5Y cells

Velagapudi

Ajileye

Okorji

et al. 2018

Phytotherapy Research

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“…Indeed, neuroinflammation and oxidative stress have been implicated in several CNS disorders, notably Alzheimer’s disease [61], [62] and Parkinson's Disease [40], [57], [63], potentiating cellular damage and pathology. The balance between oxidants and antioxidants is also fundamental to the normal physiological functioning of the CNS [64], as antioxidant processes have been shown to alleviate oxidative stress-induced damage and inflammatory responses by activated microglia [62], [65], [66]. Together, the aforementioned mechanisms are also critical in modulating responses of the irradiated CNS, and an understanding of the machinery behind neuroinflammation and redox balance can therefore help elucidate the responses of the CNS to ionising radiation at different doses.…”

Section: Microglial Responses To Stressors In the Cnsmentioning

confidence: 99%

The impact of high and low dose ionising radiation on the central nervous system

et al. 2016

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Responses of the central nervous system (CNS) to stressors and injuries, such as ionising radiation, are modulated by the concomitant responses of the brains innate immune effector cells, microglia. Exposure to high doses of ionising radiation in brain tissue leads to the expression and release of biochemical mediators of ‘neuroinflammation’, such as pro-inflammatory cytokines and reactive oxygen species (ROS), leading to tissue destruction. Contrastingly, low dose ionising radiation may reduce vulnerability to subsequent exposure of ionising radiation, largely through the stimulation of adaptive responses, such as antioxidant defences. These disparate responses may be reflective of non-linear differential microglial activation at low and high doses, manifesting as an anti-inflammatory or pro-inflammatory functional state. Biomarkers of pathology in the brain, such as the mitochondrial Translocator Protein 18 kDa (TSPO), have facilitated in vivo characterisation of microglial activation and ‘neuroinflammation’ in many pathological states of the CNS, though the exact function of TSPO in these responses remains elusive. Based on the known responsiveness of TSPO expression to a wide range of noxious stimuli, we discuss TSPO as a potential biomarker of radiation-induced effects.

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“…Under unstimulated conditions, the negative regulator Kelch-like EcH-associated protein 1 (Keap1) maintains Nrf2 in the cytoplasm, which results in its ubiquitination and proteasomal degradation. during electrophilic stress, Keap1 is altered and Nrf2 translocates to the nucleus, binds to the antioxidant response element (ARE) promotor sequence, and activates the transcription of its target genes, including HO-1 and NQO1 (12,13). Genetic and pharmacological studies indicate that both NQO1 and HO-1 provide neuroprotection.…”

Section: Petasites Japonicus Bakkenolide B Inhibits Lipopolysaccharidmentioning

confidence: 99%

Petasites japonicus bakkenolide B inhibits lipopolysaccharide‑induced pro‑inflammatory cytokines via AMPK/Nrf2 induction in microglia

et al. 2017

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Abnormal neuroinflammatory responses have diverse roles in neuronal death, oxidative stress and neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Microglia regulate these responses via molecular signaling cascades that involve inflammatory cytokines and complement proteins. Bakkenolide B from Petasites japonicus exhibits significant anti‑inflammatory and anti‑allergic bioactivities. The present study investigated the anti‑neuroinflammatory effects and underlying molecular mechanisms of bakkenolide B on the lipopolysaccharide (LPS)‑mediated neuroinflammatory response in microglia. The results indicated that bakkenolide B pretreatment significantly reduced microglial production of interleukin (IL)‑1β, IL‑6, IL‑12, and tumor necrosis factor (TNF)‑α. Furthermore, this effect was associated with reduced production of reactive oxygen species. The role of bakkenolide B was then evaluated in the upregulation of nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. The results suggested that bakkenolide B significantly upregulated Nrf2/ARE pathway‑related downstream factors, such as NADPH dehydrogenase quinone‑1 (NQO‑1) and heme oxygenase‑1 (HO‑1). Silencing of Nrf2, HO‑1 and NQO‑1 diminished the anti‑neuroinflammatory properties of bakkenolide B. AMP‑activated protein kinase (AMPK) activates the Nrf2/ARE signaling pathway, and the results of the present study demonstrated that bakkenolide B increased AMPK phosphorylation in microglia. In addition, an AMPK inhibitor abolished the bakkenolide B‑induced increase in nuclear Nrf2, NQO‑1 and HO‑1 protein expression. Finally, an AMPK inhibitor diminished the bakkenolide B‑mediated inhibition of LPS‑stimulated TNF‑α production. Taken together, the present results demonstrate that bakkenolide B may be an effective and therapeutically relevant AMPK/Nrf2 pathway activator for suppressing abnormal neuro-inflammation in neurodegenerative diseases.

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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 bioflavonoids 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

Cited by 67 publications

References 33 publications

Agathisflavone isolated from Anacardium occidentale suppresses SIRT1‐mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe‐transfected SH‐SY5Y cells

Agathisflavone isolated from Anacardium occidentale suppresses SIRT1‐mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe‐transfected SH‐SY5Y cells

The impact of high and low dose ionising radiation on the central nervous system

Petasites japonicus bakkenolide B inhibits lipopolysaccharide‑induced pro‑inflammatory cytokines via AMPK/Nrf2 induction in microglia

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