Cur(Que)min: A neuroactive permutation of Curcumin and Quercetin for treating spinal cord injury

Kumar, Pradeep; Choonara, Yahya E.; Modi, Girish; Naidoo, Dinesh; Pillay, Viness

doi:10.1016/j.mehy.2014.01.019

Cited by 15 publications

(10 citation statements)

References 55 publications

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“…Furthermore, quercetin has been demonstrated to act as a monoamine oxidase inhibitor (Chimenti et al, 2006). Additionally, other flavonoids have been shown to affect GABA A receptor-favoring mechanisms, thereby contributing to their anxiolytic effect (Anderson et al, 2012; Karim et al, 2011; Kumar et al, 2014). However, the risk assessment and anxiolytic effect of quercetin on 3xTg-AD mice has not yet to be reported.…”

Section: Discussionmentioning

confidence: 99%

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice

et al. 2015

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Alzheimer’s disease (AD) is the most common senile dementia in the world. Although important progress has been made in understanding the pathogenesis of AD, current therapeutic approaches provide only modest symptomatic relief. In this study, we evaluated the neuroprotective effect of quercetin (25 mg/kg) administration via i.p. injection every 48 hours for 3 months on aged (21–24 months old) triple transgenic AD model (3xTg-AD) mice. Our data show that quercetin decreases extracellular β-amyloidosis, tauopathy, astrogliosis and microgliosis in the hippocampus and the amygdala. These results were supported by a significant reduction in the paired helical filament (PHF), β-amyloid (βA) 1–40 and βA 1–42 levels and a decrease in BACE1-mediated cleavage of APP (into CTFβ). Additionally, quercetin induced improved performance on learning and spatial memory tasks and greater risk assessment behavior based on the elevated plus maze test. Together, these findings suggest that quercetin reverses histological hallmarks of AD and protects cognitive and emotional function in aged 3xTg-AD mice.

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Section: Discussionmentioning

confidence: 99%

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice

et al. 2015

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“…Preclinically, curcumin alone or curcumin in combination with quercetin has been shown eff ective for treating spinal cord injury by reducing the oxidative damage (8)(9)(10). Curcumin a enuated the spinal cord ischemia-reperfusion injury in rabbits by reducing the oxidative damage (10).…”

Section: Introductionmentioning

confidence: 99%

Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

Chang

Chen

Yü

et al. 2014

Food. Technol. Biotechnol.

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SummaryGlutamate is a major excitatory neurotransmi er present in the central nervous system. The glutamate/cystine antiporter system x c -connects the antioxidant defense with neurotransmission and behaviour. Overactivation of ionotropic glutamate receptors induces neuronal death, a pathway called excitotoxicity. Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases including cerebral ischemia, Alzheimer's and Huntington's disease. Curcuma has a wide spectrum of biological activities regarding neuroprotection and neurocognition. By reducing the oxidative damage, curcumin a enuates a spinal cord ischemia-reperfusion injury, seizures and hippocampal neuronal loss. The rat pheochromocytoma (PC12) cell line exhibits many characteristics useful for the study of the neuroprotection and neurocognition. This investigation was carried out to determine whether the neuroprotective eff ects of curcumin can be observed via the glutamate-PC12 cell model. Results indicate that glutamate (20 mM) upregulated glutathione peroxidase 1, glutathione disulphide, Ca 2+ infl ux, nitric oxide production, cytochrome c release, Bax/Bcl-2 ratio, caspase-3 activity, lactate dehydrogenase release, reactive oxygen species, H 2 O 2 , and malondialdehyde; and downregulated glutathione, glutathione reductase, superoxide dismutase and catalase, resulting in enhanced cell apoptosis. Curcumin alleviates all these adverse eff ects. Conclusively, curcumin can eff ectively protect PC12 cells against the glutamate-induced oxidative toxicity. Its mode of action involves two pathways: the glutathione-dependent nitric oxide-reactive oxygen species pathway and the mitochondria-dependent nitric oxide-reactive oxygen species pathway.

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“…Natural polyphenolic compounds such as curcumin, quercetin, resvaterol, oleuropein, and epigallocatechin act as antioxidants and are reported for their efficacy in improving the pathophysiological condition caused by traumatic neural injuries. The authors recently hypothesized the combinatorial potential of two specific polyphenols, curcumin (a diferuloylmethane) and quercetin (a flavonoid), in providing neuro-restriction, -repair, -regeneration, -restoration and -reorganization post-SCI [6]. Extending the above hypothesis, this article explores the potential of curcumin and quercetin as inhibitors of calpain activity employing three independent in silico molecular modeling techniques: static lattice atomistic simulations (molecular mechanics), molecular dynamics simulations, and molecular docking studies.…”

Section: Introductionmentioning

confidence: 99%

In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis

2014

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Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain's proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM), molecular dynamics (MD), and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin) and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM) demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain-calpain inhibitor molecular complexes' energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.

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Cur(Que)min: A neuroactive permutation of Curcumin and Quercetin for treating spinal cord injury

Cited by 15 publications

References 55 publications

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice

The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice

Curcumin-Protected PC12 Cells Against Glutamate-Induced Oxidative Toxicity

In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis

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