PMID: 

Curr Pharm Des. 2012 ;18(1):4-14. PMID: 22211685

Abstract Title: 

Protective effects of chronic green tea consumption on age-related neurodegeneration.

Abstract: 

Dietary antioxidant compounds, due to their pivotal role in the modulation of cellular redox mechanisms, are gaining attention of researchers in the field of brain aging and related degenerative diseases. In this perspective, green tea (GT) can be an excellent resource, as it contains large amounts of brain-accessible polyphenols. Many of these compounds are monomeric catechins, which have been shown to exert antioxidant effects, acting directly as radical scavengers or metal-chelators. In the current article, we review the general properties of GT, the direct antioxidant action of its polyphenols and the fine modulation of signaling systems related to survival and antioxidant defenses in the central nervous system of aging rats. The effects in the glutathione system and the activation of several transcription factors including cyclic AMP response element-binding (CREB) protein, levels of the brain-derived neurotrophic factor (BDNF) and the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) are given in detail. We discuss also the beneficial action of catechins in learning and memory with a particular focus on the hippocampal formation. We conclude that GT polyphenols can have a promising role in the reversal of age-related loss of neuronal plasticity and recovery after neuronal lesions associated with aging.

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PMID: 

Neuroscience. 2012 Aug 30 ;218:257-67. Epub 2012 May 23. PMID: 22634505

Abstract Title: 

Theaflavin ameliorates behavioral deficits, biochemical indices and monoamine transporters expression against subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.

Abstract: 

Evidence from clinical and experimental studies indicates that degeneration of nigrostriatal dopaminergic neurons is a pathological hallmark of Parkinson's disease (PD). The present study was designed to investigate the neuroprotective potential of theaflavin (TF) on oxidative stress, monoamine transporters and behavioral abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration. TF, a black tea polyphenol, has been known to possess neuroprotective effects against ischemia, Alzheimer's disease and other neurodegenerative disorders, but the mechanisms underlying its beneficial effects on MPTP-induced dopaminergic neurodegeneration are poorly defined. Administration of MPTP (30 mg/kg bw for four consecutive days) led to increased oxidative stress and reduced behavior patterns (open field, rotarod and hang test), nigrostriatal dopamine transporter (DAT) (immunohistochemistry and Western blot) and vesicular monoamine transporter 2 (VMAT2) (Western blot) expressions. Pre-treatment with TF reduces oxidative stress, improves motor behavior and expression of DAT and VMAT2 in striatum and substantia nigra. These results indicate that TF might be beneficial in mitigating MPTP-induced damage of dopaminergic neurons, possibly via its neuroprotective and its antioxidant potential.

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PMID: 

Biochim Biophys Acta. 2012 Nov ;1818(11):2502-10. Epub 2012 May 23. PMID: 22634381

Abstract Title: 

Polyphenolic compounds are novel protective agents against lipid membrane damage byα-synuclein aggregates in vitro.

Abstract: 

Cumulative evidence now suggests that the abnormal aggregation of the proteinα-synuclein (αS) is a critical factor in triggering neurodegeneration in Parkinson's disease (PD). In particular, a fundamental pathogenetic mechanism appears to involve targeting of neuronal membranes by soluble oligomeric intermediates of αS, leading to their disruption or permeabilisation. Therefore, a model assay was developed in which fluorophore-loaded unilamellar vesicles were permeabilised by soluble oligomers, the latter formed by aggregation of human recombinant αS protein. The αS oligomers induced an impairment of membrane integrity similar to that of the pore-forming bacterialpeptide gramicidin. The lipid vesicle permeabilisation assay was then utilised to screen 11 natural polyphenolic compounds, 8 synthetic N'-benzylidene-benzohydrazide compounds and black tea extract for protection against membrane damage by wild-type and mutant (A30P, A53T) synuclein aggregates. A select group of potent inhibitory compounds included apigenin, baicalein, morin, nordihydroguaiaretic acid, and black tea extract. Structure-activity analysis further suggests that a 5,7-dihydroxy-chromen-4-one moiety appears to be favourable for the inhibition reaction. In conclusion, we have identified a group of polyphenols that can effectively hinder membrane damage by αS aggregates. These may serve as a viable source of lead compounds for the development and design of novel therapeutic agents in PD.

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PMID: 

. PMID: 22593921

Abstract Title: 

Botanical Phenolics and Neurodegeneration.

Abstract: 

Many vegetables, fruits, grains, roots, flowers, and seeds are rich in polyphenolic compounds, and they offer beneficial effects in protecting against diseases involving oxidative stress, such as cancers and cardiovascular and neurodegenerative diseases. Although the mechanisms through which these compounds exert beneficial effects are not well understood, there is a general consensus that they possess antioxidant and anti-inflammatory properties, and are capable of chelating metal ions (Rice-Evans and Miller 1997; Martin et al. 2002; Ndiaye et al. 2005; Sun et al. 2008). Recent studies further reveal that some compounds may contribute specific biochemical effects that are beyond their antioxidant and radical-scavenging properties, for example, involvement in alterations of members of the “vitagene” system, such as heme oxygenase-1 (HO-1), heat shock protein (Hsp) 70, thioredoxin, and sirtuins. These effects may have an impact on the onset and progression of neurodegenerative diseases and aging. The understanding of these metabolic and signaling effects of polyphenols has paved the way for novel nutritional interventions (Calabrese et al. 2008, 2009). In this chapter, we review recent studies on four botanical phenolic compounds: resveratrol from grapes, curcumin from turmeric, apocynin from Picrorhiza kurroa, and epigallocatechin (EGC)- gallate from green tea. We discuss their potential beneficial effects in the prevention and treatment of neurodegenerative diseases, with an emphasis on AD, PD, and stroke.

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PMID: 

Recent Pat CNS Drug Discov. 2012 Dec ;7(3):205-17. PMID: 22742421

Abstract Title: 

In the rush for green gold: Can green tea delay age-progressive brain neurodegeneration?

Abstract: 

It is evident that brain aging engages changes in biological systems linked to synaptic function and cell metabolism and in the capacity to cope with different stresses that are either idiopathic in nature, or subject to environmental insults. In a substantial segment of the aging population there is a pathological transition to cognitive and behavioral dysfunction and thus, age constitutes the primary risk factor for Alzheimer's disease and other neurodegenerative disorders. To address the etiological complexity of aging and age-associated conditions, a new paradigm gaining increasing acceptance considers the use of multi-targeted ligands or combination of drugs to modulate several targets at once. During the past years intensive efforts are dedicated to the implementation of life style habits such as exercise and dietary compounds/supplements in combination with symptomatic treatment drugs to improve age-related cognitive decline and to attenuate motor and neurological dysfunction in neurodegenerative diseases. The catechin polyphenols constituents of green tea, which were for long time regarded merely as dietary antioxidants, have caught our and other scientist's attention because of their diverse pharmacological activities, which have been allied to a possible beneficial action on brain health. This review will elaborate on the impact of nutritional supplementation on brain function in general, and provide a compilation of the most updated literature on epidemiology, clinical and animal studies with green tea polyphenols in age-associated cognitive decline and in fighting neurodegenerative diseases. To conclude, a future perspective on the utility and assigned patents with green tea constituents will be presented.

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PMID: 

Brain Res. 2013 Feb 25 ;1497:1-14. Epub 2012 Dec 1. PMID: 23206800

Abstract Title: 

Beneficial effects of natural phenolics on levodopa methylation and oxidative neurodegeneration.

Abstract: 

Levodopa (L-DOPA) is widely used for symptomatic management in Parkinson's disease. We recently showed that (-)-epigallocatechin-3-gallate, a tea polyphenol, not only inhibits L-DOPA methylation, but also protects against oxidative hippocampal neurodegeneration. In the present study, we sought to determine several other common dietary phenolics, namely, tea catechins [(+)-catechin and (-)-epicatechin] and a representative flavonoid (quercetin), for their ability to modulate L-DOPA methylation and to protect against oxidative hippocampal injury. A combination of in vitro biochemical assays, cell culture-based mechanistic analyses, and in vivo animal models was used. While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. The stronger in vivo effect of (+)-catechin on L-DOPA methylation compared to the other dietary compounds is due to its better bioavailability in vivo. In addition, (+)-catechin strongly reduces glutamate-induced oxidative cytotoxicity in HT22 mouse hippocampal neurons in vitro through inactivation of the nuclear factor-κB signaling pathway. Administration of (+)-catechin also exerts a strong neuroprotective effect in the kainic acid-induced oxidative hippocampal neurodegeneration model in rats. In conclusion, (+)-catechin is a dietary polyphenolic that may have beneficial effects in L-DOPA-based treatment of Parkinson patients by inhibiting L-DOPA methylation plus reducing oxidative neurodegeneration.

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PMID: 

Curr Pharm Biotechnol. 2014 ;15(4):362-72. PMID: 24938889

Abstract Title: 

Polyphenols: well beyond the antioxidant capacity: gallic acid and related compounds as neuroprotective agents: you are what you eat!

Abstract: 

Gallic acid (3,4,5-trihydroxybenzoic acid) is a phenolic acid widely distributed in many different families of higher plants, both in free state, and as a part of more complex molecules, such as ester derivatives or polymers. In nature, gallic acid and its derivatives are present in nearly every part of the plant, such as bark, wood, leaf, fruit, root and seed. They are present in different concentrations in common foodstuffs such as blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, tea, wine and so on. After consumption, about 70% of gallic acid is adsorbed and then excreted in the urine as 4-O-methylgallic acid. Differently, the ester derivatives of gallic acid, such as catechin gallate ester or gallotannins, are hydrolyzed to gallic acid before being metabolized to methylated derivatives. Gallic acid is a well known antioxidant compounds which has neuroprotective actions in different models of neurodegeneration, neurotoxicity and oxidative stress. In this review, we discuss about the neuroprotective actions of gallic acid and derivatives and their potential mechanisms of action.

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PMID: 

J Neurotrauma. 2015 Feb 1 ;32(3):170-84. Epub 2014 Nov 10. PMID: 25025489

Abstract Title: 

(-)-Epigallocatechin-3-gallate modulates spinal cord neuronal degeneration by enhancing growth-associated protein 43, B-cell lymphoma 2, and decreasing B-cell lymphoma 2-associated x protein expression after sciatic nerve crush injury.

Abstract: 

Our previous studies have established that (-)-epigallocatechin-3-gallate (EGCG) has both neuroprotective and -regenerative capacity after sciatic nerve injury. Moreover, this improvement was evident on the behavioral level. The aim of this study was to investigate the central effects of ECGC on spinal cord motor neurons after sciatic nerve injury. Our study showed that administering 50 mg/kg intraperitoneally i.p. of EGCG to sciatic nerve-injured rats improved their performance on different motor functions and mechanical hyperesthesia neurobehavioral tests. Histological analysis of spinal cords of EGCG-treated sciatic nerve-injured (CRUSH+ECGC) animals showed an increase in thenumber of neurons in the anterior horn, when compared to the naïve, sham, and saline-treated sciatic nerve-injured (CRUSH) control groups. Additionally, immunohistochemical study of spinal cord sections revealed that EGCG reduced the expression of glial fibrillary acidic protein and increased theexpression of growth-associated protein 43, a marker of regenerating axons. Finally, EGCG reduced the ratio of B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 and increased the expression of survivin gene. This study may shed some light on the future clinical use of EGCG and its constituents inthe treatment of peripheral nerve injury.

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PMID: 

Life Sci. 2020 Feb 1 ;242:117250. Epub 2019 Dec 31. PMID: 31899225

Abstract Title: 

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity.

Abstract: 

BACKGROUND: Endocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity.MATERIALS AND METHOD: Male Wistar rats weighing 160-190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg; p.o.), cadmium chloride (5mgkgp.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method.RESULTS: Administration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations.CONCLUSION: The present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.

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PMID: 

J Microbiol Biotechnol. 2020 Feb 18. Epub 2020 Feb 18. PMID: 32066217

Abstract Title: 

Phenolic Profiles of Hardy Kiwifruits and Their Neuroprotective Effects on PC-12 and SH-SY5Y Cells against Oxidative Stress.

Abstract: 

Hardy kiwifruits (Planch.) have high amounts of antioxidants, including ascorbic acid (vitamin C) and phenolics. The anti-cholinesterase activity and neuroprotective effects of three different cultivars of hardy kiwifruits, cv. Mansu (×), cv. Haeyeon (), and cv. Chiak (), on PC-12 and SH-SY5Y cells were evaluated. Extraction of phenolics and vitamin C was carried out using 80% (v/v) aqueous ethanol and metaphosphoric acid assisted with homogenization, respectively. Hardy kiwifruit of cv. Mansu showed higher total phenolic, total flavonoid, and vitamin C contents and antioxidant capacity compared to the other two cultivars of hardy kiwifruits, cv. Haeyeon and cv. Chiak. Analysis of high-performance liquid chromatography results revealed the presence of procyanidin B2, (-)-epicatechin, neochlorogenic acid, cryptochlorogenic acid, rutin, hyperoside, isoquercitrin, and astragal in hardy kiwifruits. The three cultivars of hardy kiwifruits had a wide range of vitamin C content of 55.2-130.0 mg/100 g fresh weight. All three cultivars of hardy kiwifruits had protective effects on neuronal PC-12 and SH-SY5Y cells exposed to hydrogen peroxide by increasing cell viability and reducing intracellular oxidative stress. Furthermore, the hardy kiwifruits inhibited acetylcholinesterase and butyrylcholinesterase. Collectively, these results suggest that hardy kiwifruits rich in antioxidants like phenolics and vitamin C have good potential as functional materials in neuroprotective applications.

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