Pomegranate ellagitannin-gut microbial-derived metabolites, urolithins, inhibit neuroinflammation <i>in vitro</i>

DaSilva, Nicholas A.; Nahar, Pragati; Ma, Hang; Eid, Aseel; Wei, Zhengxi; Meschwitz, Susan; Zawia, Nasser H.; Slitt, Angela L.; Seeram, Navindra P.

doi:10.1080/1028415x.2017.1360558

Cited by 67 publications

(70 citation statements)

References 40 publications

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“…Uro‐A showed multiple biological activities in a variety type of cell. In particular, Uro‐A inhibited neuroinflammation and reduced oxidative stress in neuronal cells, which were highly relevant to ischemic neuronal injury. Autophagy suppresses neuroinflammation and attenuates oxidative stress in ischemic brains.…”

Section: Discussionmentioning

confidence: 97%

Urolithin A‐activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo

Ahsan

Zheng

et al. 2019

CNS Neurosci Ther

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Aim Mitochondrial autophagy (mitophagy) clears damaged mitochondria and attenuates ischemic neuronal injury. Urolithin A (Uro‐A) activates mitophagy in mammal cells and Caenorhabditis elegans. We explored neuroprotection of Uro‐A against ischemic neuronal injury. Methods Mice were subjected to middle cerebral artery occlusion. The brain infarct and neurological deficit scores were measured. The N2a cells and primary cultured mice cortical neurons were subjected to oxygen‐glucose deprivation and reperfusion (OGD/R). Uro‐A was incubated during OGD/R, and cell injury was determined by MTT and LDH. Autophagosomes were visualized by transfecting mCherry‐microtubule‐associated protein 1 light chain 3 (LC3). The protein levels of LC3‐II, p62, Translocase Of Inner Mitochondrial Membrane 23 (TIMM23), and cytochrome c oxidase subunit 4 isoform 1 (COX4I1) were detected by Western blot. The ER stress markers, activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP), were determined by reverse transcription‐polymerase chain reaction (RT‐PCR). Results Urolithin A alleviated OGD/R‐induced injury in N2a cells and neurons and reduced ischemic brain injury in mice. Uro‐A reinforced ischemia‐induced autophagy. Furthermore, Uro‐A‐conferred protection was abolished by 3‐methyladenine, suggesting the requirement of autophagy for neuroprotection. However, mitophagy was not further activated by Uro‐A. Instead, Uro‐A attenuated OGD/R‐induced ER stress, which was abolished by 3‐methyladenosine. Additionally, neuroprotection was reversed by ER stress inducer. Conclusion Urolithin A protected against ischemic neuronal injury by reinforcing autophagy rather than mitophagy. Autophagy activation by Uro‐A attenuated ischemic neuronal death by suppressing ER stress.

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Section: Discussionmentioning

confidence: 97%

Urolithin A‐activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo

Ahsan

Zheng

et al. 2019

CNS Neurosci Ther

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“…whole fruit extract ↓H 2 O 2 -induced oxidative stress; ↓apoptosis; natural antioxidants for skin health [37] whole fruit extract antimicrobial activity against 29 clinical Clostridium difficile isolates [38] juice extract inhibition of a-glucosidase activity [39] extract and juice prebiotic effect [40] juice ↓lipogenesis and lipolysis [41] juice inhibition of lipase, α-glucosidase and dipeptidyl peptidase-4 [42] peel extract inhibition of renal cell carcinoma growth [43] peel extract anti-neurodegenerative [44] peel extract ↑apoptosis and ↓metastasis in prostate cancer cells [45] peel and juice extract inhibition of cariogenic bacteria [46,47] peel and fruit extract stimulates osteoblastic differentiation (osteoporosis) [48,49] peel polysaccharide immunostimulatory effect [50] punicalagin antiproliferative activity against human lung, breast, cervical and prostate cancer cells [51][52][53] punicalagin ↑papillary thyroid human carcinoma cell death [54] punicalagin inhibition of lipopolysaccharide-induced memory impairment (Alzheimer's disease) [55] punicalagin attenuates osteoclast differentiation (osteoporosis) [56] pomegranate-derived products (juice, extract, oil) photo-chemopreventive effect in human reconstituted skin [57] urolithins inhibition of neuroinflammation (Alzheimer's disease) [58] 3.1.…”

Section: Derivative Effect Referencesmentioning

confidence: 99%

“…Several studies have proposed the use of pomegranate, and especially its derivative punicalagin and urolithins, as a potential nutritional strategy in slowing the progression of neurodegenerative disorders such as Alzheimer's disease [64]. Urolithins inhibit neuroinflammation [58], while punicalagin inhibits lipopolysaccharide-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms [55].…”

Section: Obesity Diabetes Alzheimer's Disease Osteoporosis and Denmentioning

confidence: 99%

Food Applications and Potential Health Benefits of Pomegranate and its Derivatives

Kandylis

Kokkinomagoulos

2020

Foods

161

108

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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.

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“…Pomella® is a patented commercial pomegranate fruit extract that has been studied by our group and others for a wide range of biological effects using in vitro models as well as in animals and human subjects . While we have previously reported on the isolation and structure elucidation (by NMR spectroscopy) of 21 phenolic compounds, including a new ellagitannin, named pomellatannin, from this pomegranate fruit extract , it has not yet been comprehensively characterized by LC–MS/MS.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography coupled with time‐of‐flight tandem mass spectrometry for comprehensive phenolic characterization of pomegranate fruit and flower extracts used as ingredients in botanical dietary supplements

Liu

Seeram

2018

J of Separation Science

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Pomegranate (Punica granatum L.) fruit and flower extracts, which are rich sources of bioactive phenolics, are widely utilized as ingredients in botanical dietary supplements. While the phenolic characterization of extracts of pomegranate fruit has been previously studied by liquid chromatography with tandem mass spectrometry, there is lack of similar data for pomegranate flowers. Herein, liquid chromatography with time-of-flight tandem mass spectrometry was utilized to comprehensively characterize the phenolics present in two pomegranate extracts, previously studied for their in vitro and in vivo biological effects, namely, a patented commercial pomegranate fruit extract (Pomella®), and a pomegranate flower extract. Seventy-one phenolics were characterized in the pomegranate fruit extract with the vast majority identified in the flower extract. However, only the pomegranate fruit extract contained tannin-glucuronides and two punicalagin isomers (a characteristic pomegranate phenolic) were identified in this extract while four were identified in the flower extract. The previously reported compounds, pomellatannin and punicatannins A/B, were identified as unique chemical markers in the pomegranate fruit and flower extracts, respectively. This study will aid in the quality control, authentication, and standardization of these botanical ingredients to evaluate their potential health benefits in future planned pre-clinical and clinical studies. Also, this is the first phenolic characterization of a pomegranate flower extract using liquid chromatography with tandem mass spectrometry.

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Pomegranate ellagitannin-gut microbial-derived metabolites, urolithins, inhibit neuroinflammation in vitro

Abstract: The attenuation of neuroinflammation by urolithins may contribute, in part, toward pomegranate's neuroprotective effects against AD.

Cited by 67 publications

References 40 publications

Urolithin A‐activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo

Urolithin A‐activated autophagy but not mitophagy protects against ischemic neuronal injury by inhibiting ER stress in vitro and in vivo

Food Applications and Potential Health Benefits of Pomegranate and its Derivatives

Liquid chromatography coupled with time‐of‐flight tandem mass spectrometry for comprehensive phenolic characterization of pomegranate fruit and flower extracts used as ingredients in botanical dietary supplements

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