Synergistic neuroprotection by epicatechin and quercetin: Activation of convergent mitochondrial signaling pathways

Nichols, Matthew; Zhang, J.; Polster, Brian M.; Elustondo, Pia A.; Thirumaran, Aruloli; Pavlov, Evgeny; Robertson, George S.

doi:10.1016/j.neuroscience.2015.09.012

Cited by 77 publications

(49 citation statements)

References 155 publications

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“…Studies have shown that these mitochondrial events are correlated to increased apoptotic cell death in the brain and resulting cognitive impairments in ischemic transgenic mice. Importantly, oxygen glucose deprivation–induced neuronal death was protected by the administration of a mitochondria‐targeted antioxidant (Nichols et al, ). Moreover, recent studies on transient cerebral ischemia in a mouse model of AD (5xFAD mice) have shown that hypoxia significantly exacerbates brain mitochondrial dysfunction, inclusive of mitochondrial respiration deficits, and suppresses levels of mitochondrial fusion proteins including optic atrophy‐1 and mitofusin‐2, and these changes were correlated to decrements in spatial learning and memory scores.…”

Section: Mitochondrial Dysfunction Inflammasomes and Neuroinflammatmentioning

confidence: 99%

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Calabrese

Giordano

Signorile

et al. 2016

J of Neuroscience Research

118

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Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally associated with neurovascular degeneration, in which neuronal damage and blood-brain barrier alterations coexist and evoke beta-amyloid-induced oxidative and nitrosative stress, mitochondrial dysfunction, and inflammasome- promoted neuroinflammation, which contribute to and exacerbate the course of disease. Vascular cognitive impairment comprises a heterogeneous group of cognitive disorders of various severity and types that share a presumed vascular etiology. The present study reviews major pathogenic factors involved in VaD, highlighting the relevance of cerebrocellular stress and hormetic responses to neurovascular insult, and addresses these mechanisms as potentially viable and valuable as foci of novel neuroprotective methods to mitigate or prevent VaD. © 2016 Wiley Periodicals, Inc.

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Section: Mitochondrial Dysfunction Inflammasomes and Neuroinflammatmentioning

confidence: 99%

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Calabrese

Giordano

Signorile

et al. 2016

J of Neuroscience Research

118

View full text Add to dashboard Cite

show abstract

“…98 Following oxygen-glucose deprivation, neuronal viability is rescued by 2 via the Akt-eNOS pathway and CREB activation. 94 In a mouse model of diabetes, 2 reduces oxidative stress in cardiac tissue by inducing MB. 99 Similarly, in mouse models of cardiovascular disease, 2 acts through the δ-opioid receptor to prevent mitochondrial swelling and to increase respiration; 95, 100 it can also decrease cardiac ischemia-reperfusion injury through NO and cGMP generation.…”

Section: Natural Productsmentioning

confidence: 99%

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

2016

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Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

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“…The mode of action of flavonoids and other polyphenols is increasingly associated with their ability to modulate specific cell targets and signal transduction pathways, and not only to the direct and nonspecific effects resulting from their radical scavenging capacities . Interestingly, most of the protective flavonoids are effective in the 1–10 μM range on in vitro studies using cell death models where mitochondrial dysfunction and intrinsic apoptosis are implicated or evidenced, for example by caspase‐9/‐3 activation, mitochondrial depolarization, or cytochrome c (Cyt c ) mitochondrial release . This similarity of effective concentrations, independent of the class of flavonoid, does not correlate with their differential free radical scavenging capacity .…”

Section: Introductionmentioning

confidence: 99%

Correlation between the potency of flavonoids for cytochrome c reduction and inhibition of cardiolipin‐induced peroxidase activity

2017

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There are large differences between flavonoids to protect against apoptosis, a process in which cytochrome c (Cyt c) plays a key role. In this work, we show that 7 of 13 flavonoids studied have a capacity to reduce Cyt c similar or higher than ascorbate, the flavonols quercetin, kaempferol and myricetin, flavanol epigallocatechin-gallate, anthocyanidins cyanidin and malvidin, and the flavone luteolin. In contrast, the kaempferol 3(O)- and 3,4'(O)-methylated forms, the flavanone naringenin, and also apigenin and chrysin, had a negligible reducing capacity. Equilibrium dialysis and quenching of 1,6-diphenyl-1,3,5-hexatriene fluorescence experiments showed that flavonoids did not interfere with Cyt c binding to cardiolipin (CL)/phosphatidylcholine (PC) vesicles. However, the CL-induced loss of Cyt c Soret band intensity was largely attenuated by flavonoids, pointing out a stabilizing action against Cyt c unfolding in the complex. Moreover, flavonoids that behave as Cyt c reductants also inhibited the pro-apoptotic CL-induced peroxidase activity of Cyt c, indicating that modulation of Cyt c signaling are probable mechanisms behind the protective biological activities of flavonoids. © 2016 BioFactors, 43(3):451-468, 2017.

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Synergistic neuroprotection by epicatechin and quercetin: Activation of convergent mitochondrial signaling pathways

Cited by 77 publications

References 155 publications

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Major pathogenic mechanisms in vascular dementia: Roles of cellular stress response and hormesis in neuroprotection

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

Correlation between the potency of flavonoids for cytochrome c reduction and inhibition of cardiolipin‐induced peroxidase activity

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