Article

Long Term (15 Months) Dietary Supplementation with Pomegranates from Oman Attenuates Cognitive and Behavioural Deficts in a Transgenic Mice Model of Alzheimer's Disease

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Abstract

Objective Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Results APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD.

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... In adult male rats, pre-administration with pomegranate extract has provided dose-dependent neuroprotection against cerebral ischemia-reperfusion (I/R) brain injury and DNA damage via antioxidant, anti-inflammatory, and anti-apoptotic action [7]. Pomegranate juice and extracts have also been shown to act neuro-protectively against Alzheimer's disease (AD) in animal models [8][9][10][11][12][13][14]. In older subjects with age-associated memory complaints, who drank 8 ounces of pomegranate juice for four weeks, a significant improvement in verbal and visual memory as well as an increase in plasma Trolox-equivalent antioxidant capacity was observed. ...
... Despite the considerable effort devoted to the studies on beneficial effects of pomegranate in animal models of AD [9][10][11][12][13][14] and H-I brain injury [6,7,21], there is a gap for research involving experimental models of PD in vivo. To the best of our knowledge, merely two studies referring to this subject have been performed [22,23] and their findings were diverse. ...
... With regard to pomegranate, as mentioned earlier, there is a research bias away from PD. Studies on the neuroprotective properties of pomegranate have mainly focused on AD in animal models [9][10][11][12][13][14]. To the best of our knowledge, only a few studies were performed using a PD model [22,23]. ...
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Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate’s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites—urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and α-synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and α-synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.
... The effect of dietary supplementation of pomegranate extract (PE) on memory, anxiety, and learning skills in AD mouse model possessing double Swedish APP mutation has been examined by Subash et al. (50). The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. ...
... The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. The study suggested that pomegranates intake may slow the progression of cognitive and behavioral impairments in AD (50). The mechanism of action was investigated by Ahmed et al. (51) who used aged transgenic mice AD model to evaluate the effects of a standardized PE on spatial function of longterm and working memory, APP and Aβ levels and other biomarkers of AD in brain tissues. ...
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A general review exploring the effects of pomegranates, grapes and berries and their biophenols on cognitive function in healthy subjects and their protective effects on cognitive deficits in normal aging, mild cognitive impairment, Alzheimer’s disease (AD), cerebral hypoperfusion using both animal models and human studies.
... The effect of dietary supplementation of pomegranate extract (PE) on memory, anxiety, and learning skills in AD mouse model possessing double Swedish APP mutation has been examined by Subash., et al [50]. The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. ...
... The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. The study suggested that pomegranates intake may slow the progression of cognitive and behavioral impairments in AD [50]. The mechanism of action was investigated by Ahmed., et al. [51] who used aged transgenic mice AD model to evaluate the effects of a standardized PE on spatial function of long-term and working memory, APP and Aβ levels and other biomarkers of AD in brain tissues. ...
... The effect of dietary supplementation of pomegranate extract (PE) on memory, anxiety, and learning skills in AD mouse model possessing double Swedish APP mutation has been examined by Subash et al. (51). The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. ...
... The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. The study suggested that pomegranates intake may slow the progression of cognitive and behavioral impairments in AD (51). The mechanism of action was investigated by Ahmed et al. (52) who used aged transgenic mice AD model to evaluate the effects of a standardized PE on spatial function of longterm and working memory, APP and Aβ levels and other biomarkers of AD in brain tissues. ...
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Cognitive impairment presents with limited therapeutic options. Berries, pomegranates and grapes are polyphenol-rich fruits that have both antioxidant and anti-inflammatory effects. This review aims to explore the effects of these fruits and their biophenols on cognitive function in healthy subjects and their protective effects on cognitive deficits in normal aging, mild cognitive impairment, Alzheimer’s disease (AD), cerebral hypoperfusion using both animal models and human studies.
... The effect of dietary supplementation of pomegranate extract (PE) on memory, anxiety, and learning skills in AD mouse model possessing double Swedish APP mutation has been examined by Subash., et al [50]. The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. ...
... The study showed that the transgenic mice with APP mutation that were fed a diet containing 4% PE developed significant improvements in memory, learning, locomotors function as well as a reduction in anxiety, compared with transgenic mice fed the standard chow diet. The study suggested that pomegranates intake may slow the progression of cognitive and behavioral impairments in AD [50]. The mechanism of action was investigated by Ahmed., et al. [51] who used aged transgenic mice AD model to evaluate the effects of a standardized PE on spatial function of long-term and working memory, APP and Aβ levels and other biomarkers of AD in brain tissues. ...
Article
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Decline in cognitive function can be observed in normal aging, MCI, neurodegenerative disorders, cerebral hypoperfusion and post-surgery. Cognitive impairment presents with limited therapeutic options. Berries, pomegranates and grapes are polyphenol-rich fruits that have both antioxidant and anti-inflammatory effects. This review aims to explore the effects of these fruits and their biophenols on cognitive function in healthy subjects and their protective effects on cognitive deficits in normal aging, mild cognitive impairment, Alzheimer's disease (AD), cerebral hypoperfusion using both animal models and human studies. MEDLINE® and Proquest Central data bases were searched to retrieve articles used in this general review according to specific inclusion criteria. Independently, two researchers have summarized the study characteristics and assessed quality of methodology. Meta-analysis was not possible due to the limited number of studies and marked heterogeneity, and thus results were presented as a narrative review. Biophenol-rich fruits have been shown to exert cognitive functions boosting and enhanced memory in children and healthy adults. In patients with age related cognitive decline, MCI and AD, Biophenols-rich fruits showed a marked enhancement of memory and verbal fluency with reduced dementia risk, and in artery graft and valve surgery, pomegranate protected against memory impairment. Animal studies have shown that biophenols intake enhanced cognition in AD models presumably due to a reduction of Amyloidβ plaque deposition, inflammatory cytokines, microgliosis (glial cells hypertrophy), and brain DNA protection. In conclusion, large scale studies are urgently needed to fully evaluate the preventive and/or adjunctive therapy of biophenol-rich fruits in cognitive decline, deficit and Alzheimer disease.
... More recent mouse studies examining the consumption of pomegranate peel extract showed increased brainderived neurotrophic factor expression and reduced Aβ plaque density, AChE activity, lipid peroxidation, and pro-inflammatory cytokine expression (192). These results were similar to other APP transgenic mouse studies in which pomegranate juice supplementation improved learning and memory and reduced Aβ plaque deposition (193) and showed significant improvements in memory, learning, and locomotor function while reducing anxiety (194). Another recent mouse study showed that pomegranate supplementation protected against proton irradiation-induced anxiety (195). ...
... Given that AD is progressive, insidious, and ultimately fatal disease effecting a significant portion of older individuals, delaying the onset of AD by even a slight margin would significantly impact its incidence. Mounting epidemiological and experimental evidence suggests that a lifetime of consuming an abundance of neuroprotective phytochemicals may provide significant protection from environmental and agerelated insults that accelerate the progression of AD neuropathology (76,194,333). Furthermore, diets containing a wide variety of bioactive phytochemicals from multiple plant sources may provide synergistic benefits over supplementing with isolated compounds (334,335). ...
... Effect References fruit ↓of progression of cognitive and behavioral impairments in Alzheimer's disease [65] whole fruit extract anti-inflammatory and antioxidant effects [66] whole fruit extract ↓apoptosis and inflammation in liver cells [67] peel polysaccharide ↓weight loss and ↑immune organ index of immunosuppressed mice [68] peel polysaccharide protection against CCl4-induced liver injury [69] pomegranate aril extract inhibition of contact hypersensitivity of allergic dermatitis [70] juice ↑hypoxia-induced fetal growth and ↓apoptosis in the placenta in pregnant mice [71] juice neuroprotection and protection against oxidative damage in Parkinson's disease rat model [72] juice antileishmanial activity, probably by boosting the endogenous antioxidant activity in female BALB/c mice [73] leaf ↓total serum cholesterol and triglycerides of hyperlipidemic mice [74] peel extract contribution in prevention and treatment of Giardia lamblia infection [75] peel extract preventing bone loss associated with ovariectomy in mice [48] 3.2.1. Obesity, Diabetes ...
... The addition of pomegranates in the diet may slow the progression of cognitive and behavioral impairments in Alzheimer's disease [65], while pomegranate extracts have been shown to have antiinflammatory and antioxidant effects on cecal ligation and puncture-induced acute liver injury [66]; they have also been shown to protect against arsenic-induced inflammation and apoptosis in the liver cells of male Swiss albino mice [67]. Another important product of the pomegranate with several health benefits is the pomegranate peel polysaccharides (rhamnose, glucuronic acid, galacturonic acid, glucose and xylose), which may be used in efficacious adjacent immunopotentiating therapy or an alternative means in lessening chemotherapy-induced immunosuppression; they can also be utilized as immunostimulants for the food and pharmaceutical industries [68]. ...
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Pomegranate (Punica granatum L.) is an ancient fruit that is particularly cultivated in west Asia, though it is also cultivated in the Mediterranean region and other parts of the world. Since ancient years, its consumption has been associated with numerous health benefits. In recent years, several in vitro and in vivo studies have revealed its beneficial physiological activities, especially its antioxidative, antimicrobial and anti-inflammatory properties. Furthermore, human-based studies have shown promising results and have indicated pomegranate potential as a protective agent of several diseases. Following that trend and the food industry’s demand for antioxidants and antimicrobials from natural sources, the application of pomegranate and its extracts (mainly as antioxidants and antimicrobials), has been studied extensively in different types of food products with satisfactory results. This review aims to present all the recent studies and trends in the applications of pomegranate in the food industry and how these trends have affected product’s physicochemical characteristics and shelf-life. In addition, recent in vitro and in vivo studies are presented in order to reveal pomegranate’s potential in the treatment of several diseases.
... Several phytochemicals normally present in foods, such as polyphenols, have antiinflammatory effects on microglia (Joseph et al., 2009;Peña-Altamira et al., 2017;Fernandes et al., 2018). In particular, pomegranates contain high levels of antioxidant polyphenolic substances, as compared to other fruits and vegetables (Subash et al., 2014(Subash et al., , 2015. It was also suggested that silibinin, a polyphenol isolated from milk thistle, exhibits neuroprotective activity by attenuating oxidative damage and astrocyte activation (Fernandes et al., 2018). ...
... Fruits and vegetables (Nelson et al., 2000;Okamoto et al., 2009;Pupillo et al., 2018) (Nieves et al., 2016), IE (Johnson et al., 1997;Cho et al., 2018) Carotenoids IE (Fitzgerald et al., 2013) IE (Cho et al., 2018), P (Sherry, 2017) Polyphenols IE (Patel and Hamadeh, 2009;Fernandes et al., 2018;Rosenbohm et al., 2018) IE (Scapagnini et al., 2011;Braidy et al., 2013;Subash et al., 2015), P (Bishop, 2014;Shackel, 2014;Sherry, 2017;Swinnard, 2018) Curcumin IE (Eckert et al., 2013) (Bedlack, 2018;Chico et al., 2018;Harrison et al., 2018), IE (Calabrese et al., 2008;Scapagnini et al., 2011;Dong et al., 2014;Chico et al., 2016), P (Bishop, 2014) Gingko biloba IE (Mattson et al., 2002;Patel and Hamadeh, 2009) IE (Ferrante et al., 2001;Mattson et al., 2002;Singh et al., 2019), P (Shackel, 2014;Sherry, 2017) NRF2 activator (including luteolin and resveratrol) (Harrison et al., 2018), IE (Wruck et al., 2007;Calabrese et al., 2008;ALSUntangled Group, 2011), P (Bishop, 2014) Cannabidiol (Ngo et al., 2017;Harrison et al., 2018), P (Sherry, 2017;Vivian, 2017) Glutathione (Harrison et al., 2018), P (ALSUntangled Group, 2018) Coconut oil IE (ALSUntangled Group, 2012), P (Machlan, 2012;Shackel, 2014;Sherry, 2017) Vit. A IE (Patel and Hamadeh, 2009;Rosenbohm et al., 2018) (Sofic et al., 2005), P (ALSUntangled Group, 2018) Vit. ...
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It may seem useless to propose preventive measures for a disease without established pathogenesis and successful therapy, such as amyotrophic lateral sclerosis (ALS). However, we will show that ALS shares essential molecular mechanisms with aging and that established anti-aging strategies, such as healthy diet or individually adjusted exercise, may be successfully applied to ameliorate the condition of ALS patients. These strategies might be applied for prevention if persons at ALS risk could be identified early enough. Recent research advances indicate that this may happen soon.
... More recent mouse studies examining the consumption of pomegranate peel extract showed increased brainderived neurotrophic factor expression and reduced Aβ plaque density, AChE activity, lipid peroxidation, and pro-inflammatory cytokine expression (192). These results were similar to other APP transgenic mouse studies in which pomegranate juice supplementation improved learning and memory and reduced Aβ plaque deposition (193) and showed significant improvements in memory, learning, and locomotor function while reducing anxiety (194). Another recent mouse study showed that pomegranate supplementation protected against proton irradiation-induced anxiety (195). ...
... Given that AD is progressive, insidious, and ultimately fatal disease effecting a significant portion of older individuals, delaying the onset of AD by even a slight margin would significantly impact its incidence. Mounting epidemiological and experimental evidence suggests that a lifetime of consuming an abundance of neuroprotective phytochemicals may provide significant protection from environmental and agerelated insults that accelerate the progression of AD neuropathology (76,194,333). Furthermore, diets containing a wide variety of bioactive phytochemicals from multiple plant sources may provide synergistic benefits over supplementing with isolated compounds (334,335). ...
Article
Alzheimer's disease affects millions of people, yet, there are only a limited number approaches for it pharmacological treatment. Thus, identifying factors that decrease the risk of developing Alzheimer's disease is of paramount importance. A growing body of epidemiological and experimental evidence suggests that dietary fruits and vegetables have neuroprotective effects against the harmful effects of oxidative stress, neuroinflammation, and aging. These effects are mediated by various phytochemical compounds found in plants that exhibit antioxidant, anti-inflammatory, and other beneficial properties. This review addresses epidemiological and experimental evidence for the effects and potential mechanisms of several commonly consumed phytochemicals on neuropathology and outcomes of Alzheimer's disease. Based on available evidence, we suggest that regular consumption of bioactive phytochemicals from a variety of fruits and vegetables attenuates age- and insult-related neuropathology in Alzheimer's disease.
... 5 Published studies support the neuroprotective effects of pomegranate juice and extracts against AD pathogenesis in several transgenic AD animal models. [6][7][8][9][10] Our group has also reported on the neuroprotective effects of an ellagitannin-enriched pomegranate extract (PE) in a transgenic AD animal (R1. 40) model. ...
... Comparisons are made using H 2 O 2 where P < 0.05 *, P < 0.01 **, P < 0.001 ***, P < 0.0001 ****. inhibit neuroinflammation in both in vitro and in vivo studies 19,20 and several, including curcumin, 21 olive oil, 22 grape, 23 and pomegranate, [6][7][8][9][10][11] show protective effects against neurodegenerative diseases including, AD, in cell and rodent models. However, the poor systemic bioavailability and low blood-brain barrier penetrability of polyphenols remain as major challenges toward their advancement as dietary agents for AD prevention and/or treatment. ...
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Objectives: Urolithins, ellagitannin-gut microbial-derived metabolites, have been reported to mediate pomegranate's neuroprotective effects against Alzheimer's disease (AD), but there are limited data on their effects against neuroinflammation. Herein, we: (1) evaluated whether urolithins (urolithins A and B and their methylated derivatives) attenuate neuroinflammation in murine BV-2 microglia and human SH-SY5Y neurons, and (2) evaluated hippocampus of transgenic AD (R1.40) mice administered a pomegranate extract (PE; 100 or 200 mg/kg/day for 3 weeks) for inflammatory biomarkers. Methods: Effects of urolithins (10 μM) on inflammatory biomarkers were evaluated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. In a non-contact co-culture cell model, SH-SY5Y cell viability was assessed after exposure to media collected from LPS-BV-2 cells treated with or without urolithins. Effects of urolithins on apoptosis and caspase 3/7 and 9 release from H2O2-induced oxidative stress of BV-2 and SH-SY5Y cells were assessed. Hippocampal tissues of vehicle and PE-treated transgenic R1.40 mice were evaluated for gene expression of inflammatory biomarkers by qRT-PCR. Results: Urolithins decreased media levels of nitric oxide, interleukin 6 (IL-6), prostaglandin E2, and tumor necrosis factor alpha from LPS-BV-2 microglia. In the co-culture cell model, media from LPS-BV-2 cells treated with urolithins preserved SH-SY5Y cell viability greater than media from cells treated without urolithins. Urolithins mitigated apoptosis and caspase 3/7 and 9 release from H2O2-induced oxidative stress of BV-2 and SH-SY5Y cells. While not statistically significant, inflammatory biomarkers (TNF-α, COX-2, IL-1, and IL-6) appeared to follow a decreasing trend in the hippocampus of high-dose PE-treated animals compared to controls. Discussion: The attenuation of neuroinflammation by urolithins may contribute, in part, toward pomegranate's neuroprotective effects against AD.
... Bioprocess. (2021) Omani PJ x X (Opara et al. 2009;Subash et al. 2015) Page 17 of 29 Melgarejo-Sánchez et al. Bioresour. ...
... Likewise, PJ also showed representative anti-inflammatory activity in clinical trial conditions (Aharoni et al. 2015;Achraf et al. 2018). Several long-term studies (15 months) in mice and an in vitro assay suggested that supplementation with PJ extract may slow the progression of cognitive and behavioral impairments due to Alzheimer's Disease (AD) (Subash et al. 2014(Subash et al. , 2015Velagapudi et al. 2016). These effects were mainly found for the Wonderful variety, but also for the Omani variety. ...
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Pomegranate ( Punica granatum L.) belongs to the Punicaceae plant family. It is an important fruit due to its nutritional and medicinal properties. Pomegranates are widely distributed around the world and, therefore, have a broad genetic diversity, resulting in differences in their phytochemical composition. The scientific community has focused on the positive health effects of pomegranate as a whole, but the different varieties have rarely been compared according to their bioactive compounds and bioactivity. This review aims to provide a holistic overview of the current knowledge on the bioactivity of pomegranate trees, with an emphasis on differentiating both the varieties and the different plant parts. This review intends to provide a general and organized overview of the accumulated knowledge on pomegranates, the identification of the most bioactive varieties, their potential consumption pathways and seeks to provide knowledge on the present gaps to guide future research.
... The quantification of malondialdehyde (MDA) has been reported as a good measure of the level of lipid peroxidation in biological samples [7,59]. ...
... Other studies previously described that the consumption of pomegranate (4% p/p in diet) for 15 months can reduce oxidative stress in transgenic mice for AD [7]. The proposed mechanism for antioxidant activity is the capacity of the extract to promote hydroxyl radical sink [63]. ...
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... According to Mizrahi et al. [111], punic acid, a derivative of pomegranate seed oil, shows neuroprotective activity by reducing lipid oxidation. Pomegranate phenolics, especially punicalagin, also shows great neuroprotective effects against Alzheimer's disease [112][113][114]. A study in this regard demonstrates that nanodroplet formulation of pomegranate seed oil can decrease the lipid oxidation, thus stopping the neuronal death in transgenic mouse model of Alzheimer's disease. ...
... A study in this regard demonstrates that nanodroplet formulation of pomegranate seed oil can decrease the lipid oxidation, thus stopping the neuronal death in transgenic mouse model of Alzheimer's disease. Again, long-term supplementation of pomegranate in the diet (for 15 months) has shown improvement in memory and learning and decrease of anxiety in transgenic rats [113]. Ellagic acid, another derivative of pomegranate extract, has been stated for significant reduction of βA1-42-induced neurotoxicity in human cell line [115]. ...
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In recent years, considerable importance is given to the use of agrifood wastes as they contain several groups of substances that are useful for development of functional foods. As muscle foods are prone to lipid and protein oxidation and perishable in nature, the industry is in constant search of synthetic free additives that help in retarding the oxidation process, leading to the development of healthier and shelf stable products. The by-products or residues of pomegranate fruit (seeds, pomace, and peel) are reported to contain bioactive compounds, including phenolic and polyphenolic compounds, dietary fibre, complex polysaccharides, minerals, vitamins, etc. Such compounds extracted from the by-products of pomegranate can be used as functional ingredients or food additives to harness the antioxidant, antimicrobial potential, or as substitutes for fat, and protein in various muscle food products. Besides, these natural additives are reported to improve the quality, safety, and extend the shelf life of different types of food products, including meat and fish. Although studies on application of pomegranate by-products on various foods are available, their effect on the physicochemical, oxidative changes, microbial, colour stabilizing, sensory acceptability, and shelf life of muscle foods are not comprehensively discussed previously. In this review, we vividly discuss these issues, and highlight the benefits of pomegranate by-products and their phenolic composition on human health.
... Some other studies have provided evidence about foods such as pomegranate (89,90) and wheat grass (27). There are also data showing the effects of a high-fat diet (57,91), insulin resistance (92), diabetes mellitus (93)(94)(95), obesity (95,96), pesticides (20), souvenaid (97), and other combinatorial formulations (98). ...
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Alzheimer disease (AD) is a chronic neurodegenerative disease with no effective cure so far. The current review focuses on the epigenetic mechanisms of AD and how nutrition can influence the course of this disease through regulation of gene expression, according to the latest scientific findings. The search strategy was the use of scientific databases such as PubMed and Scopus in order to find relative research or review articles published in the years 2012-2015. By showing the latest data of various nutritional compounds, this study aims to stimulate the scientific community to recognize the value of nutrition in this subject. Epigenetics is becoming a very attractive subject for researchers because it can shed light on unknown aspects of complex diseases like AD. DNA methylation, histone modifications, and microRNAs are the principal epigenetic mechanisms involved in AD pathophysiology. Nutrition is an environmental factor that is related to AD through epigenetic pathways. Vitamin B-12, for instance, can alter the one-carbon metabolism and thus interfere in the DNA methylation process. The research results might seem ambiguous about the clinical role of nutrition, but there is strengthening evidence that proper nutrition can not only change epigenetic biomarker levels but also prevent the development of late-onset AD and attenuate cognition deficit. Nutrition might grow to become a preventive and even therapeutic alternative against AD, especially if combined with other antidementia interventions, brain exercise, physical training, etc. Epigenetic biomarkers can be a very helpful tool to help researchers find the exact nutrients needed to create specific remedies, and perhaps the same biomarkers can be used even in patient screening in the future.
... These include gotu kola (Centella asiatica), a green leafy vegetable (Howes & Houghton, 2012), lemon verbena (Aloysia citrodora; Abuhamdah et al., 2015), asparagus (Asparagus species; Pahwa & Goel, 2016), pomegranate (Punica granatum; Subash et al., 2015) and holy basil (Ocimum tenuiflorum; Giridharan et al., 2011). ...
Article
Cognitive decline can occur with normal ageing and in age‐related brain disorders, such as mild cognitive impairment and dementia, including Alzheimer's disease, with limited pharmacological therapies available. Other approaches to reduce cognitive decline are urgently needed, and so the role of dietary interventions or nutraceuticals has received much attention in this respect. In this review, we examine the evidence for dietary plants and their chemical constituents as nutraceuticals, relevant to both cognitive decline in normal ageing and in dementia. Pharmacological (in vitro and in vivo), clinical and epidemiological evidence is assessed for both frequently consumed plants and their dietary forms, including tea, coffee, cocoa (chocolate), red wine, grapes, citrus and other fruits; in addition to plants used less frequently in certain diets, and that cross the blurred boundaries between foods, nutraceuticals and medicinal plants. For the latter, turmeric, saffron, sage, rosemary and lemon balm are examples of those discussed.
... Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with Alzheimer's disease (44) . The studies shows, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the Alzheimer's disease transgenic mouse. ...
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Parkinson’s disease (PD) is a gradually growing abnormality of the CNS (Central Nervous System). The definite causation and cure for this disease is not known till date. It is a chronic disease that affects the systems associated with the mobility functions of the body. There is no known remedy till now, that can cure Parkinson’s disease. Modified diet protocols for those who affected by Parkinson’s disease, works by restoring essential biochemical parameters to normal level and also by promoting good and healthy lifestyle. The most promising approach appears to be the use of antioxidants to slow down the oxidation and damage to the substantia nigra portion of the brain, which has important role in reward and movement functions. The best diet guidance for people with this disease is, to have the right balance of nutrients from different food groups. Such a balance can only be achieved by consuming a well balanced diet, which will provide adequate levels of vitamins and minerals. In addition to switching to well balanced diet, research could lead to development of additional nutritional approaches in the future that could prove effective in treatment of Parkinson’s disease.
... Healthful eating patterns such as the Mediterranean diet, have been shown to offer protective effects on brain function, such as memory and cognitive processes [5,6]. A growing number of data indicates that native Mediterranean herbs and spices are within those components of the Mediterranean diet involved in memory and cognitive enhancement [7][8][9][10][11][12]. ...
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Background Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.
... Additionally, rutin (buckwheat) and its aglycone quercetin (red onion) have both been reported to be effective as protectors of cognitive and emotional function in AD mice models [132,133]. Administration studies of red raspberries (anthocyanin and ellagitannin) and pomegranate polyphenolic compounds (anthocyanin and ellagic acid, catechins) have also reported promising results in attenuating cognitive deficits of AD [134,135]. Nevertheless, the mechanisms of action of most polyphenols are not fully understood, and further studies focusing on GM actions and interactions may be relevant to this purpose. ...
Article
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Purpose of the Review An unbalanced microbiota (dysbiosis) has been associated with or causative for a large array of human pathologies, including cognitive/emotional-related disorders. This review focuses on recent findings that address the restoration of a dysbiotic microbiota by dietary interventions with the main purpose of influencing brain function. Recent Findings Recent research strongly suggests a critical connection between dietary habits, cognitive performance, and microbiota, but a thorough study of this inter-relationship presents a significant challenge. Although gut microbiota composition may be altered by environmental variables, it is fairly stable during adulthood and old age, and the analysis of gut microbial composition is not enough to fully understand the impact of a nutritional intervention in the gut microbiota and its consequences on the brain. Novel findings suggest the need for including the analysis of the metabolome and specific biomarkers of the microbial metabolism for the understanding of the effect of nutritional interventions on brain function. Summary This review explores evidences pointing towards diet having a pivotal impact on the host’s development and progression of mental disorders through the regulation of microbiota composition and functionality. It is also discussed the role of key microbial metabolites as essential biomarkers to a better understanding of the complexity of the inter-relationship between microbiota, diet, and mental health.
... Our findings in this study demonstrated that APP/PS1 transgenic mice exhibited severe memory loss. Recent reports have indicated that dietary supplementation with pomegranate extract (PE), which is ultimately metabolized by gut microflora to yield UA, ameliorated the loss of synaptic-structure proteins and improved behavioral performance in APPsw/Tg 2576 mice [24,25] and APP/PS1 mice [26]. In contrast, another study reported that PE did not improve the cognitive performance of transgenic AD mice [27]. ...
Article
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Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by an abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and impaired neurogenesis. Urolithin A (UA), a gut-microbial metabolite of ellagic acid, has been reported to exert anti-inflammatory effects in the brain. However, it is unknown whether UA exerts its properties of anti-inflammation and neuronal protection in the APPswe/PS1ΔE9 (APP/PS1) mouse model of AD. Methods Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia, Aβ deposition, and neurogenesis. The expression of inflammatory mediators were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The modulating effects of UA on cell signaling pathways were assayed by Western blotting. Results We demonstrated that UA ameliorated cognitive impairment, prevented neuronal apoptosis, and enhanced neurogenesis in APP/PS1 mice. Furthermore, UA attenuated Aβ deposition and peri-plaque microgliosis and astrocytosis in the cortex and hippocampus. We also found that UA affected critical cell signaling pathways, specifically by enhancing cerebral AMPK activation, decreasing the activation of P65NF-κB and P38MAPK, and suppressing Bace1 and APP degradation. Conclusions Our results indicated that UA imparted cognitive protection by protecting neurons from death and triggering neurogenesis via anti-inflammatory signaling in APP/PS1 mice, suggesting that UA might be a promising therapeutic drug to treat AD.
... However, there are few papers reporting on correlating the ATR-MIR spectra of grain with their concentrations of biochemically active compounds such as anthocyanins, phenolics and other antioxidant compounds which have known cardiovascular and neurological benefits in sufficient quantities (Subash et al., 2015, Rodriguez-Mateos et al., 2019. This paper discusses recent ATR-MIR research from our laboratory and possible implications and/or applications for future work. ...
Conference Paper
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Given the high production and consumption rates of grains worldwide, rapid methods for the assessment of their biochemical composition would be of great usefulness for researchers, producers and consumers alike. Here, we report on the usefulness of attenuated total reflectance mid-infrared spectroscopy (ATR-MIR) for detecting and quantifying biochemically active constituents in Australian grains and pulses. Chemometric techniques such as principal component analysis (PCA) and partial least squares (PLS) regression show promise for predicting protein, total phenolic, monomeric anthocyanin and total antioxidant capacity in wheat. In the future, similar non-invasive techniques for biochemical analysis may be utilised by all stakeholders in view of providing equitable premiums for grain crops with high levels of nutritionally and medically beneficial phytochemical compositions.
... Thus, we postulate in utero POM exposure may lead to improved maturation, via neuroprotective mechanisms such as axonal sparing and/or remyelination. This appears to be supported by evidence of improved motor function in association with pomegranate supplementation in mice models of cytotoxic radiation [79], and cognitive and behavioral improvements in mouse models of Alzheimer's [80], implicating a role for enhanced synaptic plasticity [81]. ...
Article
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Polyphenol-rich pomegranate juice has been shown to have benefit as a neuroprotectant in animal models of neonatal hypoxic-ischemia. No published studies have investigated maternal polyphenol administration as a potential neuroprotectant in at-risk newborns, such as those with intrauterine growth restriction (IUGR). This was a randomized, placebo-controlled, double-blind pilot study to investigate the impact of maternal pomegranate juice intake in pregnancies with IUGR, on newborn brain structure and function at term-equivalent age (TEA). Mothers with IUGR at 24-34 weeks' gestation were recruited from Barnes-Jewish Hospital obstetrical clinic. Consented mothers were randomized to treatment (8 oz. pomegranate juice) or placebo (8 oz. polyphenol-free juice) and continued to take juice daily from enrollment until delivery (mean 20.1 and 27.1 days, respectively). Infants underwent brain MRI at TEA (36-41 weeks' gestation). Brain measures were compared between groups including: brain injury score, brain metrics, brain volumes, diffusion tensor imaging and resting state functional connectivity. Statistical analyses were undertaken as modified intention-to-treat (including randomized participants who received their allocated intervention and whose infants received brain MRI) and per-protocol (including participants who strictly adhered to the protocol, based on metabolite status). Seventy-seven mothers were randomized to treatment (n = 40) or placebo (n = 37). Of these, 28 and 27 infants, respectively, underwent term-equivalent MRI. There were no group differences in brain injury, metrics or volumes. However, treatment subjects displayed reduced diffusivity within the anterior and posterior limbs of the internal capsule compared with placebo. Resting state functional connectivity demonstrated increased correlation and covariance within several networks in treatment subjects, with alterations most apparent in the visual network in per-protocol analyses. Direct effects on health were not found. In conclusion, maternal pomegranate juice intake in pregnancies with known IUGR was associated with altered white matter organization and functional connectivity in the infant brain, suggesting differences in brain structure and function following in utero pomegranate juice exposure, warranting continued investigation. Clinical trial registration. NCT00788866, registered November 11, 2008, initial participant enrollment August 21, 2012.
... Metabolome analysis revealed that pomegranate aril, seed, rind, flower, bark and root contain a wide range of phytochemicals, including gallotannins, ellagic acid, flavonoids, antioxidants, terpenoids and alkaloids (Mayuoni-Kirshinbaum and Porat 2014;Ophir et al. 2014;Ahmed et al. 2014;Aslan et al. 2014;Bellesia et al. 2014;Caliskan and Bayazit 2013). Pomegranate is one of the important commercial fruit crops across the world and considered to be valuable because of the health-promoting traits in edible and nonedible parts of the fruit that can be used for a wide range of human diseases including cancers, diabetics, obesity, Alzheimer's disease and hypertension (Jalikop et al. 2005;Dassprakash et al. 2012;Malviya et al. 2014;Mehrzadi et al. 2014;Rafieian-Kopaei et al. 2014;Subash et al. 2015;Bellesia et al. 2014;Wang et al. 2015). Genetic diversity studies of pomegranate have been carried out by several groups in India, Turkey, Morocco, Iran, Tunisia, Spain, Italy and China who used various molecular marker tools (Ajal et al. 2014;Ercisli et al. 2011a, b;Ferrara et al. 2014;Narzary et al. 2010;Sarkhosh et al. 2011;Caliskan and Bayazit 2013;Noormohammadi et al. 2012;Omayma et al. 2014;Zeinalabedini et al. 2012;Zhang et al. 2012;Yuan et al. 2007;Zhao et al. 2013). ...
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cultivated pomegranate collections from India. Our study placed all 88 germplasm into four clusters. We identified a cultivated clade of pomegranates in close proximity to Daru types of wild-type pomegranates that grow naturally near the foothills of the Himalayas. Admixture analysis sorted various lineages of cultivated pomegranates to their respective ancestral forms. We identified four linked markers for fruit weight, titratable acidity and bacterial blight severity. PGCT001 was found associated with both fruit weight and bacterial blight, and the association with fruit weight during both seasons analyzed was significant after Bonfer-roni correction. This research demonstrates effectiveness of microsatellites to resolve population structure among the wild and cultivar collection of pomegranates and future use for association mapping studies.
... Hanish Singh et al. [67] reported that ethanolic extract of Alpinia galangal improved the antioxidant status and inhibited the acetylcholine esterase activity in AD mice. Our research group from Oman reported the beneficial effects of natural products including pomegranate and figs on AD transgenic mice models [62,[68][69][70][71][72][73][74][75][76][77]. ...
Article
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Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer’s disease (AD), impairments in the movement, Parkinson’s disease (PD), and the inability to walk, talk, and think, Huntington’s disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.
... The neuroprotective effect of pomegranate phytochemicals has been demonstrated against hypoxia-ischemia (H-I) [14,15] and cerebral ischemiareperfusion (I/R) brain injuries [16]. Regarding neurodegenerative diseases, a lot of in vivo studies on beneficial effects of pomegranate have been devoted to AD [17][18][19][20][21][22][23]; however, its neuroprotective potential against PD is based on very limited data [13,24,25]. We recently suggested that pomegranate's neuroprotective effect is mediated by urolithin A (UA)-a colonic microbiota ETs-derived metabolite [13]. ...
Article
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Pomegranate juice (PJ) is a rich source of ellagitannins (ETs), precursors of colonic metabolite urolithin A, which are believed to contribute to pomegranate’s neuroprotective effect. While many experimental studies involving PJ’s role in Alzheimer’s disease and hypoxic-ischemic brain injury have been conducted, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. Previously, we have reported that PJ treatment improved postural stability, which correlated well with enhancement of neuronal survival, protection against oxidative damage, and α-synuclein aggregation. Since olfactory and motor deficits are typical symptoms of PD, in this study, we aimed to investigate the capability of PJ to protect against olfactory, motoric, and neurochemical alterations. To evaluate its efficiency, Wistar rats were given a combined treatment with ROT (1.3 mg/kg b.w./day, s.c.) and PJ (500 mg/kg/day, p.o.) for 35 days. After this, we assessed the olfactory discrimination index (DI) and vertical and horizontal activities as well as levels of dopamine and its main metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) in the dissected midbrain of animals. Our findings provide the first evidence that PJ treatment protects against ROT-induced DA depletion in the midbrain, which correlates well with improved olfactory function and vertical activity as well as with the presence of urolithin A in the brain.
... Since the PE was the major source of phenolics in the mouse chow, it represented the majority of mice's total daily phenolics intake which was comparable to the reported human intake values of phenolics (1000 mg) in several published studies (Scalbert and Williamson 2000;Del Rio et al. 2013). There are several published animal studies using even higher doses of PEs (up to 4%; w/w) to study their biological activities (Subash et al. 2014;Subash et al. 2015;Turrini et al. 2015;Braidy et al. 2016). Although treatment at the current dose showed no indications of toxicity (i.e. ...
Article
Diets rich in fats are linked to elevated systemic inflammation, which augments the progression of inflammatory-related disorders including non-alcoholic fatty liver disease (NAFLD) and neuro-degenerative diseases. A phenolic-enriched pomegranate fruit extract (PE) was investigated for its hepatoprotective and anti-inflammatory effects in male C57BL/6 mice fed either a high-fat diet or a standard rodent diet with or without 1% of PE for 12 weeks. Mouse livers and hippo-campi were evaluated for the expression of genes associated with NAFLD and inflammation by multiplexed gene analysis. PE alleviated diet-induced fatty liver and suppressed hepatic lipid regulating genes including Cd36, Fas, Acot2 and Slc27a1. In addition, PE suppressed gene expression of pro-inflammatory cytokines including Il-1a, Il-7, Il-11, Ifna, Tnfa and Lepr in the hippocampi. Our findings support the protective effects of PE against high-fat diet-induced hepatic and neurological disease. ARTICLE HISTORY
... Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with Alzheimer's disease (44) . The studies shows, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the Alzheimer's disease transgenic mouse. ...
... Interest has been growing in plants containing high levels of antioxidants and/or phenolics [1,2], as they have been found to provide cardiovascular and other health benefits [3][4][5]. Some of these plants have the potential for human consumption as medicinal or food purposes [6]. ...
Article
Mid-infrared spectroscopy is finding an increasing number of applications; however, many of its potential uses remain unexplored. In this study, mid-infrared spectroscopy is applied to predict total antioxidant capacity and phenolic contents of powdered matrices of 14 diverse plant species. In all instances, the optimum prediction models were found using standard normal variate smoothing as a pre-processing method. The results show high correlation between the FTIR predicted and chemically determined values, namely R 2 values of 0.962 for total phenolics, 0.829 for cupric reducing antioxidant potential (CUPRAC) and 0.911 for ferric reducing antioxidant potential (FRAP). The relative RMSE found for validation indicated that total phenolic content could be predicted with higher accuracy than CUPRAC or FRAP. This pilot study highlights the promise of this technology for plant breeders and a range of industries where rapid screening of many samples for antioxidant and/or phenolic content is envisaged.
... This finding confirms the damage reduction in the brain in the treated group compared to the intoxicated group. Our results showed that dietary supplementation with pomegranate juice significantly attenuated learning and memory deficits, improved motor coordination, and reduced anxiety [35]. Thenmozhi et al. [36] concluded that hesperidin decreased memory loss and attenuated acetylcholinesterase (AchE) activity and the amyloidogenic pathway induced by aluminum exposure. ...
Article
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Aluminum (Al) is an element with ubiquitous presence on the earth crust that may cause neuropathological, neurobehavioral, neurophysical, and neurochemical changes linked to its bioavailability. The purpose of the present study was to determine the neuroprotective potential of pomegranate juice on Al induced neurotoxicity. Three groups of 7 female albino Swiss mice were used: the control group received only drinking water; the positive control group was exposed daily to 500 mg/kg of AlCl3 orally; and the third treated group received pomegranate juice (v/v in water) supplied in dark bottles for 4 h/day followed by AlCl3 at a dose of 500 mg/kg orally for 20 h/day for 90 days. After 90 days, the mice were subjected to behavioral and memory tests. Cortex cerebral and hippocampus injuries were determined with hematoxylin and eosin staining and Al accumulation was measured by graphite furnace atomic absorption with Zeeman correction. The Al deposition in the brain caused neural degeneration and decreased cell density inducing a state of anxiety, depression, and a deficit of learning and memory. Pomegranate juice treatment attenuated neurobehavioral alterations, decreased Al in the brain and restored the histological structure. High-performance liquid chromatography with a diode-array detector (HPLC-DAD) revealed a range of bioactive molecules (i.e., gallic acid, quercetine, luteolin) in the pomegranate juice that may have neuroprotective value for the nervous disorders caused by Al intoxication.
... Due to its phenolics content, pomegranate juice (PJ) is an effective nutritional option for treating neurodegenerative injuries [18,19]. Several studies have confirmed the neuroprotective effects of PJ, demonstrating that it attenuates the cognitive and behavioral deficits of AD [20,21], protects against PD [22][23][24] and ameliorates brain antioxidant-status [25]. ...
Article
Purpose: Aluminum (Al) is a harmful metal to organisms and is capable of entering the human body in multiple ways, such as through drinking, breathing, deodorant use, and vaccination. This study examined the prospective toxicity of Al and the protective attributes of pomegranate juice (PJ) on neurobehavioral and biochemical parameters of male mice. Methods: Six groups of male mice were treated for 35 days with 20 % PJ (group II), 40 % PJ (group III), 400 mg/kg Al (group IV), Al + 20 % PJ (group V), Al + 40 % PJ (group VI) or tap water (control, group I). Behavioral assessments were conducted for learning and memory evaluations at the end of experiment. In addition, the forebrain was isolated for biochemical analysis. Results: The exposure of male mice to Al decreased learning and memory retention in the shuttle box, Morris water-maze and T-Maze tests. Biochemical analysis revealed significant depletions in neurotransmitters including DA, 5-HT and AChE and oxidative proteins including GSH, GST, CAT and SOD and increased TBARES levels in Al-treated mice compared to untreated mice. Pomegranate juice provided protection against these effects after Al exposure by ameliorating learning and memory retention and oxidative state in a dose-independent manner. Conclusion: Our data demonstrated that Al exposure caused behavioral and biochemical disorders. Pomegranate juice in lower dose has beneficial properties for health and can be used as a source of antioxidants to reduce the toxicity of Al and other substances.
... Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with Alzheimer's disease (44) . The studies shows, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the Alzheimer's disease transgenic mouse. ...
Article
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Parkinson’s disease is a gradually growing abnormality of the CNS (central nervous system). There is no definite causation and cure for this disease is known till date. It is a chronic disease and it mainly affects that portion, which is associated with the movement. There is no known remedy till date that can cure Parkinson’s disease (PD). The changing diet protocols for Parkinson’s disease work by restoring the normal biochemical level of the human body and also to promote the good and healthy lifestyle. The most promising approach appears to be the use of antioxidants to slow the oxidation and damage to the substantia nigra. The most excellent diet guidance for most people with Parkinson's to have the right balance of nutrients from different food groups. That can be achieved by eating a well-balanced diet, which will provide adequate levels of vitamins and minerals. It’s possible that additional nutritional approaches may be found in the future.
... Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving quality of life in individuals with Alzheimer's disease (44) . The studies shows, the effects of the antioxidant-rich pomegranate fruit grown in Oman on brain oxidative stress status were tested in the Alzheimer's disease transgenic mouse. ...
Chapter
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Neurodegenerative diseases (NDDs) including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are mainly affecting the aged population worldwide. According to the report of the World Health Organization, the morbidity due to NDDs will be second highest cause of death in 2040. PD is the second most common progressive NDD after AD that is characterized by resting tremor, rigidity, postural abnormalities, stooped posture, bradykinesia, akinesia and festinating gait. Symptomatic and effective treatment of PD in modern medicine is by the supplementation of the dopamine in the form of L-dopa. However, long term administration typically leads to motor complications, such as L-dopa induced dyskinesia. Current pharmacological therapies for the disease are inadequate. Unfortunately, other strategies such as neural transplantation and stem cell transplantation remain in experimental stage. The pathogenesis of PD is multifactorial with toxic reactions including inflammation the glutamatergic toxicity, the dysfunction of mitochondrial activity and of the ubiquitin/proteasome system, the activation of apoptosis pathways, the elevation of iron and nitric oxide, the alteration of the homeostasis of antioxidants/oxidants. Numerous cellular, animal and human studies have delineated the anti-parkinsonic effects of citrus fruits owning to their active components. Increased consumption of citrus fruits is associated with higher antioxidant status and phytochemical constituents, thus helpful against oxidative stress, mitochondrial dysfunction, inflammation and apoptosis that play an important role in the cause and progression of PD.The multifactorial etiology of PD suggests that drugs with multiple targets could have therapeutical potential for these pathologies.
Chapter
Fruits contribute an abundant supply of antioxidants to human diet and act as the first line of defense against the risks of chronic diseases occurrence. Pomegranate is one among the highly explored and appreciated fruits on account of its promising health-promoting and disease-preventing properties. Pomegranate fruit and its key components including rind, seed, and membranous network have been evidently reported as carriers of a wide range of bioactive compounds including ellagitannins, hydroxycinnamic acids, hydroxybenzoic acids, flavons, flavonol-3-ols, anthocyanidins, anthocyanins, and conjugated and nonconjugated fatty acids, phytosterols, vitamins, and minerals. Traditional aspects of pomegranate exploitation as remedy against infections and gastrointestinal ailments have generated a basis for the modern-age research. Findings of the research carried out in the last two decades manifest fruit, flower, seeds, and peel of pomegranate as natural strategy to treat microbiological and parasitic pathogenesis and to act as a chemopreventive and therapeutic approach against inflammatory and infectious chronic ailments. Forthcoming sections of this chapter review fundamental biochemical composition of pomegranate and its anatomical fractions and provide recent updates on pomegranate perspective applications against the risks of various forms of cancers, cardiovascular diseases, diabetes, acute and chronic liver injury, renal disorders, impaired gut health, neurodegenerative disorders, microbiological pathogenesis, and parasitic infestation.
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A spice is a part of plant such as seed, fruit, root, bark, berry, budor vegetable substance that is primarily used for flavoring, coloring or preserving food. Indian spices are used as preservative, impart good smell and flavor to food. Many of these spices, herbs, and oils have been used for health and medicinal purposes also. Turmeric, pepper, ginger, cloves, cinnamon, onion, garlic and nutmeg are found in the kitchensof almost every people of the world today. In Asian population, where people regularly consume spices, low incidence of certain neurodegenerative diseases including Parkinson’s disease (PD) is reported. For example an adult in India can consume 80-200 mg/day of curcumin, the bioactive component of turmeric or about 50 g of garlic in a week. Extensive research over the last 20 years has indicated that nutraceuticals derived from such spices as turmeric, red pepper, black pepper, licorice, clove, ginger, garlic, coriander, and cinnamon target mitochondrial and proteosome dysfunction, oxidative stress, inflammation and apoptosis, thereby preventing PD.
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Pomegranate (Punica granatum L.), the fruit and its peel have been shown to hold tremendous potential for the treatment of various ailments. Incorporation of pomegranate, peel and their extracts, as key functional ingredients in various ethnopharmacological formulations are widely accepted in almost all cultures of the World. In addition to their disease ameliorating features, pomegranate and the peel extracts have gained significant popularity in functional food market as ingredient of choice in foods designed to prevent onset of various non-communicable diseases. Health promoting features of the pomegranate peel and fruit extracts define the scope of this natural reserve in global nutraceutical and functional food industry. On account of their unique phytochemicals profile, plentiful pool of antioxidants, dietary fibers, minerals and natural colors, both the valuable reserves have been remained as highly explored plant material in last two decades. Building levels of interest in this fruit has created a deeper insight among researchers to understand actual potential and pathways of pomegranate biomolecules reactivity in human models. The chapter in hand meticulously deals with pomegranate and its extracts as source of innovative healthy components responsible for averting cardiovascular diseases, inflammatory and non-inflammatory disorders, type 2 diabetes, gastric ulcers, various types of cancers and neurodegenerative disorders.
Article
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that still has no permanent cure. The drugs prescribed in the present days are only for symptomatic relief for the patients. Many studies correlating the reduction in the incidence of AD with the diet consumed have been published. These studies showed that a diet rich in polyphenols is associated with a decrease in the incidence of AD. The present review is focused on the ability of pomegranate and its bioactive components to ameliorate the progression of AD and their ability to exert a neuroprotective effect. Various studies showing the ability of pomegranate in inhibiting enzymes, reducing reactive oxygen species, inhibition of microglial activation, inhibition of tau protein hyperphosphorylation, maintenance of synaptic plasticity, anti-inflammatory activity and its ability to inhibit Beta secretase-1 (BACE-1) has been reviewed in this article. In spite of the lack of studies on humans, there are compelling evidence indicating that pomegranate can reduce various risk factors involved in the causation of AD and thus can be used as a persistent nutraceutical to slow ageing and for providing neuroprotection for the treatment of AD. Abbreviations: ACh, Acetylcholine; AChE, Acetylcholinesterase; AD, Alzheimer’s disease; AGEs, Advanced Glycation End products; APP, Amyloid precursor protein; Aβ, Amyloid-beta; BACE, Beta secretase or β-site amyloid precursor protein cleaving enzyme; BBB, Blood brain barrier; BDNF, Brain derived neurotrophic factor; BuChE, Butyrylcholinesterase; CAM, Chick Chorioallantoic Membrane; COVID 19, Corona virus disease 19; COX, Cyclooxygenase; DPPH, 2,2 diphenyl picryl hydrazyl; ER, Endoplasmic Reticulum; FAO, Food and Agriculture organization; FDA, Food and drug administration; GFAP, Glial-fibrillar acidic protein; GPx, Glutathione peroxidase; GSH, Glutathione; GST, Glutathione S transferase; HFD, High-fat diet; IL-6, Interleukin-6; LDH, Lactate dehydrogenase; LO, Lipooxygenase; LPS, Lipopolysaccharide; MAO, Mono amine oxidase; MDA, Malondialdehyde; MedDi, Mediterranean diet; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mTOR, Mammalian Target of Rapamycin; NAD, Nicotinamide adenine dinucleotide; NFAT, Nuclear factor of activated T-cells; NO, Nitric oxide; NQO1, Quinone oxidoreductase 1; Nrf2, Nuclear factor erythroid 2-related factor 2; oAβ, Oligomeric amyloid-beta; pCREB, Cyclic AMP-Response Element Binding Protein; PGE2, Prostaglandin E2; RON, Reactive nitrogen species; ROS, Reactive oxygen species; SOD, Superoxide dismutase; STZ, Streptozotocin; TNF-α, Tumor necrosis factor α; UNESCO, The United Nations Educational, Scientific and Cultural Organization; WHO, World Health Organization.
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Sitta europaea, with 18 subspecies, has a wide distribution in deciduous forests of Eurasia. The aim of this study was to evaluate the taxonomic and phylogenetic relationships of this subspecies to European, Asian as well as Caucasian clades. 10 individuals of two populations from Zagros forests in Kermanshah and Kohgiluyeh and Boyer-Ahmad Provinces were captured with permission from Iran Department of Environment and their blood samples were collected. Furthermore, we used ND2 sequence data (1041 bp) for 136 sequences from GenBank and 10 sequences from Zagros Mts. Genetic variations and Genealogical analysis was calculated using complete ND2 gene sequence (1041bp) and TRN+G model, Bayesian trees and maximum likelihood, respectively. Median joining algorithm showed the relationships among haplotypes. We found four new haplotypes for the Zagros populations. Phylogenetic analysis indicated that Zagros populations were distinct from Caucasian clade. FST statistical values, resulting from the analysis of molecular variance represented significant variations in genetic structure among Eurasian Nuthatch populations. Moreover, FCT revealed significant variation among European, Asian and Caucasian clades. Our result suggests that Eurasian Nuthatch populations in Eurasia comprise three phylogenetic species, and likely biological species. However, the previous nomenclature subspecies, S.e. caucasian and S.e. persica, can be regarded as a common phylogenetic species.
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Chapter 9-Pomegranate has over 2000 years of cultivation history and has been described in divine scriptures, including the Holy Quran and the Old Testament. Pomegranate trees requires, an average annual water requirement of 20 m3, a dry climate, and a 5 – 8 years duration for the fruit development and ripening. Pomegranate fruits weight ranges 375 - 500 g and its edible juice arils makes up to 26.9 – 65.6% of the fruit weight. Pomegranate is the most difficult fruit to process for its juice due to the difficulty to separate the arils from the peels. Untreated pomegranate juices (PJ) contains an excessive turbidity and it must be clarified by addition of fining agents such as albumin, bentonite, gelatin kiesel gel, polyvenylpyrrolidone or ultrafiltration. In industrial processing, the juice is concentrated to reduce volume, proper storage to resist microbial and chemical deterioration, and packaging for year-round utilization. The industrial concentration is performed by removal and subsequent concentration of aroma compounds by distillation, which is then added back to the de-aromatized juice concentrate during reconstitution step to restore the original aroma profile. Processes such as different types of pasteurization, osmotic distillation, high hydrostatic pressure, microwave, and heating are applied either separate or in combination for the processing of pomegranate juice. Regardless of the processing technique, the PJ should pass specific criteria of quality control and storage stability, such as the microbiological safety, color, total soluble solids, anthocyanins content, total phenols contents, and antioxidant activities. Greater attentions have been directed to the bioactive properties of phytochemical compounds present in pomegranate. The active compounds in pomegranate possess anti-atherosclerotic, anti-atherogenic, anti-carcinogenic, anti-diabetic, anti-diarrheal and many others biological properties. It is anticipated that the use of PJ as non-pharmacological agent in the treatment of both infectious and non-communicable diseases will find wider application in the Millennium.
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Pomegranate (Punica granatum L.) in Mexico is a marginal fruit and ormanmental tree. Despite its wide adaptation, pomegranate is consumed sporadically and seasonally, usually as fresh fruit as decoration in Mexican food. In Mexico, pomegranate is also used in traditional herbolaria taking advantage of all parts of the fruit and the shrub...
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ZET Artan yaşam süresi, nüfusun yaşlanmasına ve bunun sonucunda yaşlılıkla ilişkili hastalıklara ve bakım endişelerine neden olmuştur. Bu durum bireyleri yaşlanmaya karşı korunma ve yaşlanmaya bağlı nörodejeneratif hastalıkların gelişmesini erteleme, azaltma veya tedavi etme özelliklerine sahip besinler aramaya yöneltmiştir. İnsan beyninde çeşitli nörodejeneratif etkileri önlemek için diyetsel değişik-likler, besin takviyeleri, fonksiyonel gıdalar ve nutrosötikler öne çıkmaktadır. Son yıllarda nutrasötikler, hastalıkları önlemenin kolay ve çekici bir yolu olarak sağlık pazarına girmiştir. Yaşa bağlı nörode-jenerasyon ve bilişsel düşüşü önlemek için fitokimyasal açıdan zengin besinlerle ilgili çalışmalara yoğun ilgi her geçen gün artmak-tadır. Nutrasötik besinler; endikasyonlar için formüle edilen sentetik maddeler veya kimyasal bileşikleri içeren besinler değil hastalıkları önleme ve tedavi etme özellikleri olan doğal bileşenleri içerisinde barındıran sağlıklı yiyeceklerdir. Özellikle üzümsü meyveler, üzüm, turunçgiller ve nar üzerinde araştırmalar yoğunlaşmaktadır. Bu meyvelerin tüketilmesinin, yaşla ilişkili nörodejenerasyonun ve bunun sonucunda bilişsel ve motor fonksiyon değişikliklerinin önlenmesine yardımcı olabileceği bildirilmektedir. Bu derleme, yaşlı bireylerde görülmekte olan nörolojik hastalıklara en çok etkisi olduğu düşünülen bazı nutrasötik meyvelerin olası etkileri hakkında kısa bilgiler sun-maktadır. ABSTRACT Increased lifespan has resulted in aging of the population and aging-related diseases and care concerns. This has led individuals to look for foods that have the properties of postponing, reducing or treating the development of neurodegenerative diseases associated with aging and aging. Dietary changes, nutritional supplements, functional foods, and nutraceuticals stand out to prevent various neurode-generative effects in the human brain. In recent years, nutraceuticals have entered the health market as an easy and attractive way to prevent diseases. In order to prevent age-related neurodegeneration and cognitive decline, intense interest in studies on phytochemically rich foods is increasing day by day. Nutraceutical foods; They are not foods containing synthetic compounds or chemical compounds formulated for indications, but healthy foods that contain natural ingredients that have the properties of preventing and treating diseases. In particular, research focuses on berries, grape, citrus and pomegranate. It is reported that consuming these fruits can help prevent age-related neurodegeneration and consequently cognitive and motor function changes. In this review, it provides brief information about the possible effects of some nutraceutical fruits, which are thought to have the most effect on neurological diseases in elderly individuals.
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Pomegranate (Punica granatum L.), the fruit and its peel have been shown to hold tremendous potential for the treatment of various ailments. Incorporation of pomegranate, peel and their extracts, as key functional ingredients in various ethnopharmacological formulations are widely accepted in almost all cultures of the World. In addition to their disease ameliorating features, pomegranate and the peel extracts have gained significant popularity in functional food market as ingredient of choice in foods designed to prevent onset of various non-communicable diseases. Health promoting features of the pomegranate peel and fruit extracts define the scope of this natural reserve in global nutraceutical and functional food industry. On account of their unique phytochemicals profile, plentiful pool of antioxidants, dietary fibers, minerals and natural colors, both the valuable reserves have been remained as highly explored plant material in last two decades. Building levels of interest in this fruit has created a deeper insight among researchers to understand actual potential and pathways of pomegranate biomolecules reactivity in human models. The chapter in hand meticulously deals with pomegranate and its extracts as source of innovative healthy components responsible for averting cardiovascular diseases, inflammatory and non-inflammatory disorders, type 2 diabetes, gastric ulcers, various types of cancers and neurodegenerative disorders.
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The hydrolyzable tannins ellagitannins (ETs) and ellagic acid (EA) are polyphenols present in food sources such as pomegranates, berries, and walnuts. However, they are poorly absorbed on consumption, but the gut microbiota metabolizes them. In recent decades, an extensive literature has attributed a wide range of beneficial effects to these natural compounds based on their biological activities, including antioxidant, chemopreventive, antiinflammatory, cardioprotective, etc. However, in the last decade, knowledge of their bioavailability and metabolism has prompted research into the physiological role of their in vivo metabolites generated by gut microbiota action, the urolithins, which have received recognition across the world as possible candidates for health benefits. This chapter summarizes the latest developments and knowledge on the occurrence, dietary intake, bioavailability and metabolism, and biological effects of ellagitannins and ellagic acid supplementation, paying particular attention to the activity of their gut microbiota‐derived metabolites – urolithins.
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Background: Several findings suggest neuroinflammation as a contributing factor for the onset of psychiatric disorders such as Alzheimer’s disease, depression, and anxiety. There is increasing evidence pointing out that the Mediterranean diet influences brain and behavior. Mediterranean herbs and spices have been shown to be within those components of the Mediterranean diet involved in cognitive enhancement. Thus, we investigated the influence of Mediterranean natural extracts (MNE), Rosemary extract (RE) and Glycyrrhiza glabra root extract (GGRE), on cognitive behavior. Results: Adult zebrafish were exposed to RE or GGRE (100 and 250 mg/L) treatments. Both MNE improved memory retention during the T-maze test, although no improvements were observed during the novel object preference. Similarly, chronic administration of RE (150 mg/Kg) and GGRE (150 mg/Kg) improved, respectively, spatial and retention memory, as assessed by the Morris Water Maze (MWM), and the Elevated Plus Maze (EPM) in healthy male rats. However, no improvements were observed during the novel object recognition. Finally, male, and female rats were chronically treated with lipopolysaccharide [(LPS) 300 ug/kg] and orally administered with RE. Interestingly, RE reversed LPS-induced cognitive deficit during the MWM and EPM in female rats. Conclusions: We found that MNE improved cognition in both zebrafish and rats. Moreover, MNE rescued LPS-induced cognitive impairment in a gender-specific manner. Therefore, our study supports the view that zebrafish represent a valuable preclinical model for drug discovery in neuroscience. These findings contribute to an exciting and growing body of research suggesting that MNE may play an important role in the prevention of cognitive impairment.
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Alzheimer's disease (AD), a type of dementia, severely distresses different brain regions. Characterized by various neuropathologies, it interferes with cognitive functions and neuropsychiatrical controls. This progressive deterioration has negative impacts not only on an individual's daily activity but also on social and occupational life. The pharmacological approach has always remained in the limelight for the treatment of AD. However, this approach is condemned with several side effects. Henceforth, a change in treatment approach has become crucial. Plant-based natural products are garnering special attention due to lesser side effects associated with their use. The current review emphasizes the anti-AD properties of phytoconstituents, throws light on those under clinical trials, and compiles information on their specific mode of actions against AD-related different neuropathologies. The phytoconstituents alone or in combinations will surely help discover new potent drugs for the effective treatment of AD with lesser side effects than the currently available pharmacological treatment.
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Background Aluminum is a neurotoxic element that can accumulate in the brain and cause neurodegenerative disorders. In addition, the antioxidants found in pomegranate juice (PJ) are much more than those existing in other fruits. It was proven to provide protection against neurodegenerative diseases. Objectives This experiment aimed to clarify the amelioration efficiency of PJ against aluminum chloride-induced neurobehavioral and biochemical disorders in female mice. Methods The female mice were given oral administrations for 35 days as follows. The control group received tap water, the PJ groups received 20% and 40% pomegranate juice, the aluminum chloride (AlCl3) group was treated with 400 mg/kg AlCl3, and the last two groups received AlCl3 + 20% PJ and AlCl3 + 40% PJ, respectively. The neurobehavioral features were assessed by shuttle box, T-maze, and Morris water maze devices. Furthermore, the neurotransmitters and oxidative indicators in the brains of the female mice were determined at the end of experiment. Results Significant effects of AlCl3 were observed on female mice in the body weight, during the behavioral tasks (shuttle box, T-maze, and Morris water maze), and in neurotransmitters and oxidative stress parameters. Pomegranate juice, especially at low concentrations, induced remarkable improvements in body weight, spatial memory and learning during T-maze, Morris water maze and shuttle box tasks, as well as in neurotransmitters and oxidative biomarkers in the AlCl3-treated female mice. Conclusion PJ reversed AlCl3-induced neurotoxicity and improved learning and memory in female mice. However, PJ contains a group of antioxidants that may be considered double-edged swords in the cellular redox status especially at high doses.
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Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease. Punica granatum L., (P. granatum) is one of the most important commercial crops of Oman with traditional medicinal claims. The study aimed to quantify the phenolic content of the Omani pomegranate peel extracts and to investigate their antioxidant, anti-cholinesterase activities along with computational studies for the development of AD therapy. The dried peels of P. granatum fruits were exhaustively extracted with chloroform, ethyl acetate and butanol. Peel extracts were subjected to the preliminary phytochemical screening. Colorimetric methods were used to quantify total phenolic and flavonoids contents. The neuroprotective potential of the peel extracts was evaluated by assessing the in-vitro antioxidant activity and their ability to inhibit acetylcholinesterase (AChE) enzyme activity. In-silico analysis and molecular docking of the most promising phenolic metabolite present in pomegranate peel was also carried out. The phytochemical screening showed the presence of flavonoids, tannins, alkaloids, carbohydrates and terpenoids. The total phenolic, flavonoids content & antioxidant activity was found to be higher in the butanol extract. Surprisingly, butanol extract showed slightly lower AChE inhibitory activity than chloroform extract. Catechin showed lower binding energy for AChE in comparison to Beta-secretase-1 (BACE-1). It formed three and two hydrogen bonds with AChE and BACE-1, respectively. The results of the current study provided evidence that butanol extract is rich in phenolics possesses excellent antioxidant activity. Furthermore, in silico and in-vitro studies revealed promising anti-AD activity. Further investigations must be carried out to isolate and develop the chemical constituents of pomegranate peel as neuroprotective agent(s).
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Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Changes in the oxidative stress, antioxidants, and membrane-bound enzymes were investigated in the cerebral cortex and hippocampus of AD transgenic mice model after long-term dietary supplementation of date palm fruits from Oman. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA; mice were fed two different doses of dates (such as 4 and 2%) or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls and parallel decrease in the activity of antioxidant enzymes were observed in control diet-treated Tg2576 AD mice. Dates (4 and 2%) treated APPsw/Tg2576 AD mice exhibited significantly attenuated oxidative damage, evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase). The activities of membrane-bound enzymes (Na(+), K(+)-ATPase and acetyl cholinesterase) were altered in control diet-treated APPsw/Tg2576 AD mice brain regions. Meanwhile, both the percentages of date supplementation were able to restore the activity of enzymes to comparable values observed in controls. In summary, we have shown that chronic dietary supplementation of date palm fruits grown in Oman showed possible beneficial effects concomitant with oxidative stress reduction and increased antioxidant enzymes in AD transgenic mice model. These results warrant further exploration of how anti-reactive oxygen species properties of dates offer such beneficial effects on the AD-like brain.
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Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aβ) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.
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We assessed the changes in the plasma Aβ, oxidative stress/antioxidants, and membrane bound enzymes in the cerebral cortex and hippocampus of Alzheimer's disease (AD) transgenic mice (Tg2576) after dietary supplementation of Omani figs fruits for 15 months along with spatial memory and learning test. AD Tg mice on control diet without figs showed significant impairment in spatial learning ability compared to the wild-type mice on same diet and figs fed Tg mice as well. Significant increase in oxidative stress and reduced antioxidant status were observed in AD Tg mice. 4% figs treated AD Tg mice significantly attenuated oxidative damage, as evident by decreased lipid peroxidation and protein carbonyls and restoration of antioxidant status. Altered activities of membrane bound enzymes (Na+ K+ ATPase and acetylcholinesterase (AChE)) in AD Tg mice brain regions and was restored by figs treatment. Further, figs supplementation might be able to decrease the plasma levels of Aβ (1–40, 1–42) significantly in Tg mice suggesting a putative delay in the formation of plaques, which might be due to the presence of high natural antioxidants in figs. But this study warrants further extensive investigation to find a novel lead for a therapeutic target for AD from figs.
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Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review.
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Research has shown that fruits and vegetables containing high levels of polyphenolics (flavonoids) display high total antioxidant activity. Our laboratory found that various fruit and vegetable extracts, particularly blueberry (BB), were effective in reversing age-related deficits in neuronal signaling and behavioral parameters following 8 weeks of feeding, possibly due to their polyphenolic content. However, it was unclear if these phytonutrients were able to directly access the brain from dietary BB supplementation (BBS). The present study examined whether different classes of polyphenols could be found in brain areas associated with cognitive performance following BBS. Thus, 19 month old F344 rats were fed a control or 2% BB diet for 8-10 weeks and tested in the Morris water maze (MWM), a measure of spatial learning and memory. LC-MS analyses of anthocyanins in the diet and subsequently in different brain regions of BBS and control rats were carried out. Several anthocyanins (cyanidin-3-O-beta-galactoside, cyanidin-3-O-beta-glucoside, cyanidin-3-O-beta-arabinose, malvidin-3-O-beta-galactoside, malvidin-3-O-beta-glucoside, malvidin-3-O-beta-arabinose, peonidin-3-O-beta-arabinose and delphinidin-3-O-beta-galactoside) were found in the cerebellum, cortex, hippocampus or striatum of the BBS rats, but not the controls. These findings are the first to suggest that polyphenolic compounds are able to cross the blood brain barrier and localize in various brain regions important for learning and memory. Correlational analyses revealed a relationship between MWM performance in BBS rats and the total number of anthocyanin compounds found in the cortex. These findings suggest that these compounds may deliver their antioxidant and signaling modifying capabilities centrally.
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This study examined the effects of stabilized-rice bran (SRB) rich diet on responses to stress in rats. Standard rodent diet mixed with SRB in the ratio of 2:1 and 1:1 (w/w) was given for 6 weeks to test rats. Results showed that weekly cumulative food intakes smaller in SRB rich diet treated animals were normalized at the end of the treatment. Body weights decreased and exploratory activity in an open field increased in SRB rich diet treated animals. Learning and espatial memory monitored in the Morris water test was enhanced. An episode of 2 h restraint stress decreased food intake of SRB as well as normal diet treated animals. Deficits were smaller in SRB diet than normal diet treated animals. Exposure to 2 h restraint stress increased brain serotonin (5-hydroxytryptamine, 5-HT) metabolism. The increases were smaller in SRB rich than normal diet treated animals. A potential use of SRB in health and disease is discussed in the context of its antioxidant and serotonergic effect.
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Polyphenols are the most abundant antioxidants in diet. Indeed, fruits, vegetables, beverages (tea, wine, juices), plants, and some herbs are loaded with powerful antioxidant polyphenols. Despite their wide distribution, research on human health benefits truly began in the mid-1990s (Scalbert, A.; Johnson, I. T.; Saltmarsh, M. Am. J. Clin. Nutr. 2005, 81, S15S-217S). Phenolic compounds have been receiving increasing interest from consumers and manufacturers because numerous epidemiological studies have suggested associations between consumption of polyphenol-rich foods or beverages and the prevention of certain chronic diseases such as cancers and cardiovascular diseases (Manach, C.; Mazur, A.; Scalbert, A. Curr. Opin. Lipidol. 2005, 16, 77-84; Duthie, S. J. Mol. Nutr. Food Res. 2007, 51, 665-674). Furthermore, in the past 10 years, research on the neuroprotective effects of dietary polyphenols has developed considerably. These compounds are able to protect neuronal cells in various in vivo and in vitro models through different intracellular targets (Ramassamy, C. Eur. J. Pharmacol. 2006, 545, 51-64). However, it is not at all clear whether these compounds reach the brain in sufficient concentrations and in a biologically active form to exert beneficial effects. On the other hand, it has become clear that the mechanisms of action of these polyphenols go beyond their antioxidant activity and the attenuation of oxidative stress. Therefore, there is a need for more research on their intracellular and molecular targets as special pathways underlying distinct polyphenol-induced neuroprotection. The focus of this review is aimed at presenting the role of some polyphenols from fruits, vegetables, and beverages in neuroprotection and particularly in Alzheimer's disease and the research challenges in this area.
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Objective Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available. Method Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H1 receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed. Results and Conclusion In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic‐like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders. Copyright © 2001 John Wiley & Sons, Ltd.
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Aging is the accumulation of changes that increase the risk of death. Aging changes can be attributed to development, genetic defects, the environment, disease, and the inborn aging process. The latter is the major risk factor for disease and death after age 28 in the developed countries. In these countries, average life expectancies at birth (ALE-B) now range from 76-79 years, 6-9 years less than the limit of about 85 years imposed by aging. Aging changes may be caused by free radical reactions. The extensive studies based on this possibility show promise of increasing the ALE-B to 85 years and beyond.
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The role of pomegranate on folk medicine has been largely established and in recent years a notable increase of scientific support has occurred. However, what is real? Evidence suggests that phenolic phytochemicals of pomegranate fruit, mainly anthocyanins and ellagitannins, could exert multiple therapeutic properties on health management as playing an essential role in oxidative stress balance, preventing important cardiovascular diseases, and fighting as chemoprotective agent against several kinds of cancer. In addition, pomegranate antioxidant bioactives also could possess a role as neuroprotectors in some neurological disorders just as broad antimicrobial activities among other beneficial implications. Regarding promising prospects of pomegranate phenolics, this review summarizes the available scientific information related to health promotion features of pomegranate-derived products and underlines the influence of multiple constituents on the observed biological actions, pointing out pomegranate juice as interesting source to obtain the pomegranate attributed health benefits.
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Nowadays, the interest in dietary antioxidants, mainly present in fruits and vegetables, has prompted research in the field of commercial polyphenol-rich beverages. The main objective of the present work was to produce new polyphenol-rich beverages using lemon and pomegranate juices in different proportions (at 25%, 50% and 75% for both juices). The bioactive composition (flavonoids and vitamin C) of the mixtures as well as its stability, antioxidant capacity and changes in colour over a 70 days storage period were studied. Our results suggest that the new drink made of 75% of pomegranate juice (PJ) and 25% of lemon juice (v:v), has potential for development of new healthy beverages or food products, emphasised by its high antioxidant capacity determined by its phenolic composition – punicalagin isomers, anthocyanins and vitamin C – and improved colour properties.
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Since pomegranate is a fruit tree species showing high plant diversity, molecular techniques are required to quickly and precisely characterize and certify different cultivated varieties. The study evaluates a genetic method to identify pomegranate cultivars. The procedure is based on the Restriction Fragment Length Polymorphisms (RFLP) and Polymerase Chain Reaction (PCR) techniques. Ten pomegranate accessions from the varietal groups Mollar de Elche, Mollar de Albatera, Mollar de Orihuela, Valencianas and Bordes were evaluated. The results prove the appropriateness of the PCR–RFLP technique for identifying pomegranate cultivars. All evaluated cultivars were differentiated according to their genetic profiles. There is a low correlation between pomegranate morphological and genetic traits on this study.
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Folin-Ciocalteau method of total phenolics assay, originally developed for protein determination, has recently evolved as a total antioxidant capacity assay, but found to be incapable of measuring lipophilic antioxidants due to the high affinity of FC chromophore, i.e. multivalent-charged phospho-tungsto-molybdate(V), toward water. Thus, the FC method was modified and standardized so as to enable simultaneous measurement of lipophilic and hydrophilic antioxidants in NaOH-added isobutanol-water medium. Optimal conditions were: dilution ratio of aqueous FC reagent with iso-BuOH (1:2, v/v), final NaOH concentration: 3.5×10-2 M, reaction time: 20 min, and maximum absorption wavelength: 665 nm. The modified procedure was successfully applied to the total antioxidant capacity assay of trolox, quercetin, ascorbic acid, gallic acid, catechin, caffeic acid, ferulic acid, rosmarinic acid, glutathione and cysteine, as well as of lipophilic antioxidants such as α-tocopherol (vitamin E), butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, lauryl gallate and β-carotene. The modified FC method reliably quantified ascorbic acid whereas the conventional method could not. The modified method was reproducible and additive in terms of total antioxidant capacity values of constituents of complex mixtures such as olive oil extract and herbal tea infusion. The trolox equivalent antioxidant capacities of the tested antioxidant compounds correlated well with those found by the Cupric Reducing Antioxidant Capacity reference method.
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The antioxidant activity of pomegranate juices was evaluated by four different methods (ABTS, DPPH, DMPD, and FRAP) and compared to those of red wine and a green tea infusion. Commercial pomegranate juices showed an antioxidant activity (18−20 TEAC) three times higher than those of red wine and green tea (6−8 TEAC). The activity was higher in commercial juices extracted from whole pomegranates than in experimental juices obtained from the arils only (12−14 TEAC). HPLC-DAD and HPLC-MS analyses of the juices revealed that commercial juices contained the pomegranate tannin punicalagin (1500−1900 mg/L) while only traces of this compound were detected in the experimental juice obtained from arils in the laboratory. This shows that pomegranate industrial processing extracts some of the hydrolyzable tannins present in the fruit rind. This could account for the higher antioxidant activity of commercial juices compared to the experimental ones. In addition, anthocyanins, ellagic acid derivatives, and hydrolyzable tannins were detected and quantified in the pomegranate juices. Keywords: Pomegranate; Punica granatum; Punicaceae; juice; phenolics; anthocyanins; ellagic acid; punicalagin; tannins; antioxidant activity; ABTS; DPPH; DMPD; FRAP
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Fruits of diverse pomegranate (Punica granatum L.) cultivars were analyzed for soluble phenolics content, antioxidant activity, soluble solid concentration, acidity and internal red color intensity. Analysis was carried out at various dates throughout the harvest season, corresponding to different climatic conditions during fruit ripening. Values obtained varied with cultivar and ripening date. In three cultivars of different sensory properties and harvest season, comparison between late- and early-ripening fruit revealed that arils of fruit ripening later in the season contained more soluble phenolics (1.21–1.71 compared to 0.22–0.88 pyrogallol equivalents, g L−1) and exhibited a higher antioxidant activity, as measured by the ferric reducing ability (FRAP) assay (1.22–2.37 compared to 0.86–1.95 vitamin C equivalents, g L−1). The red color intensity of the arils inversely related (R2 = 0.89–0.94) to the sum of heat units accumulated during fruit ripening. Multiple linear regression analysis on fruit characteristics in 11 diverse cultivars indicated that juice antioxidative capacity linearly correlated with soluble phenolics content (R2 = 0.98), but not with the red color intensity of the arils (R2 = 0.38). Also, no significant correlation was established between aril color and either juice pH or total soluble phenolics content. The results imply that pomegranate fruit antioxidant and sensory quality traits can be enhanced by the choice of cultivar and controlled-climate cultivation management.
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Phytochemicals, as plant components with discrete bio-activities towards animal biochemistry and metabolism are being widely examined for their ability to provide health benefits. It is important to establish the scientific rationale to defend their use in foods, as potential nutritionally active ingredients. Phytochemicals could provide health benefits as: (1) substrates for biochemical reactions; (2) cofactors of enzymatic reactions; (3) inhibitors of enzymatic reactions; (4) absorbents/sequestrants that bind to and eliminate undesirable constituents in the intestine; (5) ligands that agonize or antagonize cell surface or intracellular receptors; (6) scavengers of reactive or toxic chemicals; (7) compounds that enhance the absorption and or stability of essential nutrients; (8) selective growth factors for beneficial gastrointestinal bacteria; (9) fermentation substrates for beneficial oral, gastric or intestinal bacteria; and (10) selective inhibitors of deleterious intestinal bacteria. Such phytochemicals include terpenoids, phenolics, alkaloids and fiber. Research supporting beneficial roles for phytochemicals against cancers, coronary heart disease, diabetes, high blood pressure, inflammation, microbial, viral and parasitic infections, psychotic diseases, spasmodic conditions, ulcers, etc is based on chemical mechanisms using in vitro and cell culture systems, various disease states in animals and epidemiology of humans. However, it must be emphasized that a distinction needs to be drawn between the types of information that can be obtained from studies in vitro, in animals and in humans. Mechanisms of action must certainly be established in vitro; however, the efficacy of these same ingredients with their mechanisms of action, must also be demonstrated in vivo. The rapid growth in the use of phytochemicals in nutraceutical and functional foods requires that the food and pharmaceutical industries face new challenges: in addressing worldwide public concern over the efficacy and safety of supplements and foods claimed to be health-promoting; in government regulations related to safety, labeling and health claims for products that contain phytochemicals; in the manufacturing of foods with different qualities and stabilities; and in marketing issues, particularly as they relate to consumers' recognizing added value.© 2000 Society of Chemical Industry
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The amplified fragment length polymorphism (AFLP) analysis of DNA was used to characterize 34 pomegranate cultivars. By using a combination of six primers, a total of 327 markers were scored with a mean of 57.5. The high percentage of polymorphic bands (ppb) of 94.7 and the resolving power (Rp) collective rate value of 129.14 were scored. Data proved that the tested primers were informative to discriminate among cultivars and to survey the genetic diversity in this fruit crop. It has been assumed that the local pomegranate germplasm is characterized by a typically continuous genetic diversity. The derived dendrogram proved that cultivars are clustered independently from their geographical origin and their denomination. In addition, AFLP permitted the generation of a nearly unlimited number of molecular markers that are reliable in differentiating the cultivars and/or the polyclonal varieties.
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Important health-promoting compounds, including six types of anthocyanins, phytoestrogenic flavonoids and ellagic acid were determined individually in pomegranate juices (Punica granatum L.) of eight Iranian cultivars by high performance liquid chromatography coupled to UV–vis detector (HPLC–UV) using individual calculation from the peak area based on standard curves of each component. Total phenolics and antioxidant activities were determined by Folin–Ciocalteu and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods, respectively, and compared among the cultivars. The predominant anthocyanins were delphinidin 3,5-diglucoside (372–5301 mg/l) followed by cyanidin 3,5-diglucoside (242–2361 mg/l), delphinidin 3-glucoside (49–1042 mg/l) and pelargonidin 3,5-diglucoside (7–90 mg/l), respectively. The highest level of total tannins was found in Sweet Alak cultivar (3 mg/l). Saveh Black Leather showed the highest level of ellagic acid (160 mg/l). Antioxidant activity varied among the cultivars (18–42 Trolox equivalents antioxidant capacity) and was directly related to the total phenolics in each type of juice.
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A wealth of evidence underscores the tight link between oxidative stress, neurodegeneration and aging. When the level of excess reactive oxygen species (ROS) increases in the cell, a phenomenon characteristic of aging, DNA is damaged, proteins are oxidized, lipids are degraded and more ROS are produced, all culminating in significant cell injury. Recently we showed that in the nematode, Caenorhabditis elegans, oxidation of K(+) channels by ROS is a major mechanism underlying the loss of neuronal function. The C. elegans results support an argument that K(+) channels controlling neuronal excitability and survival might provide a common, functionally important substrate for ROS in aging mammals. Here we discuss the implications that oxidation of K(+) channels by ROS might have for the mammalian brain during normal aging, as well as in neurodegenerative diseases such as Alzheimer's and Parkinson's. We argue that oxidation of K(+) channels by ROS is a common theme in the aging brain and suggest directions for future experimentation.
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The onset of age-related neurodegenerative diseases superimposed on a declining nervous system could enhance the motor and cognitive behavioral deficits that normally occur in senescence. It is likely that, in cases of severe deficits in memory or motor function, hospitalization and/or custodial care would be a likely outcome. This means that unless some way is found to reduce these age-related decrements in neuronal funct