Pomegranate Extract Modulates Processing of Amyloid-β Precursor Proteinin an Aged Alzheimer’s Disease Animal Model

Ahmed, Aseef; Subaiea, Gehad M.; Eid, Aseel; Li, Liya; Seeram, Navindra P.; Zawia, Nasser H.

doi:10.2174/1567205011666141001115348

Cited by 42 publications

(45 citation statements)

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

Kujawska

Jourdes

Kurpik

et al. 2019

IJMS

114

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

Kujawska

Jourdes

Kurpik

et al. 2019

IJMS

114

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“…15 Under normal conditions, microglia scavenge the CNS for plaques, damaged neurons and infectious agents constantly, but when they are activated too much, large numbers of inflammatory factors associated with serious pathologies are released, aggravating nerve injury and causing harm to normal organisms. 11,16 In other words, microglial cells activate the precursors of inflammation factors.…”

Section: Discussionmentioning

confidence: 99%

Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Zhang¹,

Zou³

et al. 2015

Human Vaccines & Immunotherapeutics

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#These authors equally contributed to this work.Keywords: Ab burdens, APP/PS1 mice, continuous vaccinations, immunotherapy, inflammatory factors, microglial activation spatial learning and memory ability, specific fluctuationsAbbreviations: 4Ab1-15, 4 alternative tandem repeats of GPGPG-linked Ab1-15 sequences; Ab, b-amyloid; APP, amyloid precursor protein; IFN-g, interferon-g; IgG, immunoglobulin G; IL-1b, interleukin-1b; IL-4, interleukin-4; PS1, presenilin-1; Th, T-helper type; TNF-a, tumor necrosis factor-aThe common pathological hallmark of Alzheimer's disease (AD) is b-amyloid plaques deposition. Immunotherapy is a revolutionary pharmacological treatment for AD, aiming at improving plaque clearance while concomitantly decreasing inflammation. Our previous study prepared antigen 4Ab1-15 and found that it could alleviate pathologic alterations in APP/PS1 transgenic mice. The objective of our study was to research the changing processes induced by immunotherapy, including the inflammatory factor levels and microglial activation that is closely associated with Ab burdens clearance. APP/PS1 mice were injected with 4Ab1-15 6 times. Each time, the inflammatory factors in sera were detected, and a specific fluctuation that first increased and then decreased was found, in which there was a turning point after the third injection. It prompted us to further detect the indicators in the brains after the third injection and the sixth injection. The results showed that the therapeutic effects for Ab burdens and behaviors were continuously improved during the whole immune processes, whereas the inflammatory factor levels and microglial activation experienced similar specific fluctuations. The novel discovery may provide convenient methods for further detection and evaluation of immunotherapy in disease courses.

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“…10,15,16 Under hyperglycemic conditions, AGE formation is significantly accelerated, resulting in undesirable accumulation of modified proteins in circulation and cells. 28,29 We have recently reported on the anti-AGE effects of ellagitannins from the pomegranate fruit, 30 and were interested in whether similar effects/mechanisms of actions would be exerted by gallotannins, namely, PGG, given its central role as a biosynthetic precursor of hydrolyzable tannins in plants. [19][20][21] To date, several mechanisms have been proposed to explain the deleterious effects of AGEs.…”

Section: Introductionmentioning

confidence: 99%

The hydrolyzable gallotannin, penta-O-galloyl-β-d-glucopyranoside, inhibits the formation of advanced glycation endproducts by protecting protein structure

Liu

Frost

et al. 2015

Mol. BioSyst.

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Glycation is a spontaneous process initiated by a condensation reaction between reducing sugars and proteins that leads to the formation of advanced glycation endproducts (AGEs). The in vivo accumulation of AGEs is associated with several chronic human diseases and, thus, the search for AGE inhibitors is of great research interest. Hydrolyzable tannins (gallotannins and ellagitannins) are bioactive plant polyphenols which show promise as natural inhibitors of glycation and AGE formation. Notably, the gallotannin, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), is a key intermediate involved in the biosynthesis of hydrolyzable tannins in plants. Herein, we investigated the effects of PGG on the individual stages of protein glycation and on protein structure (using bovine serum albumin; BSA). MALDI-TOF data demonstrated that PGG inhibited early glycation by 75% while the synthetic AGE inhibitor, aminoguanidine (AG), was not active (both at 50 μM). In addition, PGG reduced the formation of middle and late stage AGEs by 90.1 and 60.5%, respectively, which was superior to the positive control, AG. While glycation induced conformational changes in BSA from α-helix to β-sheets (from circular dichroism and congo red binding studies), PGG (at 50 μM) reduced this transition by 50%. Moreover, BSA treated with PGG was more stable in its structure and retained its biophysical properties (based on zeta potential and electrophoretic mobility measurements). The interaction between PGG and BSA was further supported by molecular docking studies. Overall, the current study adds to the growing body of data supporting the anti-AGE effects of hydrolyzable tannins, a ubiquitous class of bioactive plant polyphenols.

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Pomegranate Extract Modulates Processing of Amyloid-β Precursor Proteinin an Aged Alzheimer’s Disease Animal Model

Cited by 42 publications

References 0 publications

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

The hydrolyzable gallotannin, penta-O-galloyl-β-d-glucopyranoside, inhibits the formation of advanced glycation endproducts by protecting protein structure

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