Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α

Malar, Dicson Sheeja; Venkatesan, S.; Prasanth, Mani Iyer; Balamurugan, Krishnaswamy; Devi, Kasi Pandima

doi:10.1016/j.tiv.2018.03.003

Cited by 46 publications

(31 citation statements)

References 42 publications

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“…In this work, we were inspired by the therapeutic potential of flavonoids against AD, having chrysin ( 1 ) as the lead structure [11] We focused on projecting and generating a small library of flavonoids with neuroprotective potential, while displaying a suitable physicochemical profile. For that purpose, we used the 5,7-dihydroxychromen-4-one unit as the basic building block of all flavonoid structures (aglycones and C -glucosyl derivatives) for two reasons: (a) it is present in many flavonoids exhibiting neuroprotective activities, including not only chrysin [13,14], but also apigenin [15], luteolin [16], and vitexin [17,18], among others, and (b) its synthetic precursor, 2,4,6-trihydroxyacetophenone, has the ideal electron-donating capacity to act as the sugar acceptor in C-glycosylation reactions, in contrast with other polyphenols such as hydroquinone or catechol, which favor the accomplishment of highly effective synthetic routes.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

et al. 2019

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With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.

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Section: Introductionmentioning

confidence: 99%

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

et al. 2019

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“…Lyu et al have investigated the effect of vitexin on HIF-1α, VEGF, and p38 MAPK protein expression in sevoflurane-induced newborn rat [66]. The result from this study revealed that treatment with vitexin managed to significantly suppress the expression of HIF-1α, VEGF, and p38 MAPK.…”

Section: Vitexinmentioning

confidence: 74%

Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer’s Disease

Yahaya

Zolkiffly

Moklas

et al. 2020

Journal of Immunology Research

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Alzheimer’s disease (AD) has been clinically characterized by a progressive degeneration of neurons which resulted in a gradual and irreversible cognitive impairment. The accumulation of Aβ and τ proteins in the brain contribute to the severity of the disease. Recently, vitexin compound has been the talk amongst researchers due to its pharmacological properties as anti-inflammation and anti-AD. However, the epigenetic mechanism of the compound in regulating the neuroinflammation activity is yet to be fully elucidated. Hence, this review discusses the potential of vitexin compound to have the pharmacoepigenetic property in regulating the neuroinflammation activity in relation to AD. It is with hope that the review would unveil the potential of vitexin as the candidate in treating AD.

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“…[ 31 ] Vitexin delayed the paralysis in worm and subsequently contributed to the extended lifespan, which might be due to its ability to interfere with the amino acid residues in Aβ and prevent the fibrillization of toxic oligomeric peptide. [ 22 ]…”

Section: Discussionmentioning

confidence: 99%

“…[ 20 ] Preliminary studies from our lab have identified vitexin to possess cholinesterase inhibitory activity as well as inhibitory activity against Aβ 25‐35 and glutamate‐induced toxicity in Neuro‐2a cells by augmenting antioxidant pathways and inhibiting apoptosis. [ 21‐23 ] Vitexin isolated from the leaves of Serjania erecta Radlk has also been reported to protect PC12 cells from Aβ 25‐35 ‐induced toxicity. [ 24 ] The present study was intended to evaluate the neuroprotective effect of vitexin and explore its possible mode of action in preventing Aβ proteotoxicity using transgenic C. elegans strains of AD.…”

Section: Introductionmentioning

confidence: 99%

Vitexin prevents Aβ proteotoxicity in transgenic Caenorhabditis elegans model of Alzheimer's disease by modulating unfolded protein response

Malar

Prasanth

Jeyakumar

et al. 2020

J Biochem & Molecular Tox

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Alzheimer's disease (AD) accounts for an estimated 60% to 80% of all dementia cases. The present study is aimed at evaluating the neuroprotective efficacy of vitexin, an apigenin flavone glycoside using transgenic Caenorhabditis elegans strain (CL2006) of AD. The neuroprotective effect of vitexin was determined using physiological assays, quantitative polymerase chain reaction, and Western blotting. The results of survival and paralysis assay indicate that vitexin (200 μM) significantly extended the lifespan of the nematodes. Vitexin‐treated nematodes showed a significant reduction in the expression of Aβ, ace‐1, and ace‐2 genes when compared to control. Further, vitexin significantly upregulated the expression of acr‐8 and dnj‐14, and increased the lifespan of the nematodes. Vitexin was also found to modulate the unfolded protein response genes (hsp‐4, pek‐1, ire‐1, and xbp‐1) and suppress the expression of Aβ. Overall, the results show that vitexin acts as a neuroprotective agent and protects transgenic C. elegans strains from Aβ proteotoxicity.

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Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α

Cited by 46 publications

References 42 publications

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer’s Disease

Vitexin prevents Aβ proteotoxicity in transgenic Caenorhabditis elegans model of Alzheimer's disease by modulating unfolded protein response

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