Epigallocatechin Gallate Reduces Amyloid β‐Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress‐Mediated Apoptosis

The interest in the biological properties of grapevine polyphenols (PPs) in neuroprotection is continuously growing in the hope of finding translational applications. However, there are several concerns about the specificity of action of these molecules that appear to act non-specifically on the permeability of cellular membranes. Naturally occurring neuronal death (NOND) during cerebellar maturation is a well characterized postnatal event that is very useful to investigate the death and rescue of neurons. We here aimed to establish a baseline comparative study of the potential to counteract NOND of certain grapevine PPs of interest for the oenology. To do so, we tested ex vivo the neuroprotective activity of peonidin- and malvidin-3-O-glucosides, resveratrol, polydatin, quercetin-3-O-glucoside, (+)-taxifolin, and (+)-catechin. The addition of these molecules (50 μM) to organotypic cultures of mouse cerebellum explanted at postnatal day 7, when NOND reaches a physiological peak, resulted in statistically significant (two-tailed Mann–Whitney test—p < 0.001) reductions of the density of dead cells (propidium iodide+ cells/mm2) except for malvidin-3-O-glucoside. The stilbenes were less effective in reducing cell death (to 51–60%) in comparison to flavanols, (+)-taxifolin and quercetin 3-O-glucoside (to 69–72%). Thus, molecules with a -OH group in ortho position (taxifolin, quercetin 3-O-glucoside, (+)-catechin, and peonidin 3-O-glucoside) have a higher capability to limit death of cerebellar neurons. As NOND is apoptotic, we speculate that PPs act by inhibiting executioner caspase 3.

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“…In vitro SH-SY5Y cells/human Aβ [80] In vivo APP/PS1 mouse model of AD Tunicamycin or Tapsigargin [80] Taxifolin…”

Section: Epigallocatechinmentioning

confidence: 99%

Protective Effects of Some Grapevine Polyphenols against Naturally Occurring Neuronal Death

et al. 2020

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“…EGCG, phyllanthin and hypophyllanthin have been known for their capability in protecting cellular and tissue damages from reactive oxygen species and ER stress in various cell cultures and animal models. [ 11,12,14,15,27 ] In our previous study, we demonstrated that these three polyphenolic antioxidants unexpectedly elicited different effects on indomethacin‐ and diclofenac‐induced cytotoxicity in Caco‐2 cells. [ 1 ] EGCG prevented NSAID‐induced Caco‐2 apoptosis via inhibition of CHOP‐related ER stress.…”

Section: Discussionmentioning

confidence: 99%

“…These three polyphenols have been associated with various health‐promoting effects such as antioxidant, anti‐inflammatory, anti‐microbial and cytoprotective activities. [ 10–15 ] Their cytoprotective effect may involve multi‐mechanisms, particularly reduction of cellular stresses and oxidative damages. However, cytoprotective potential and mechanisms of these antioxidants against NSAID‐induced enteropathy have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Modulation of non-steroidal anti-inflammatory drug-induced, ER stress-mediated apoptosis in Caco-2 cells by different polyphenolic antioxidants: a mechanistic study

Boonyong

Vardhanabhuti

Jianmongkol

2020

Journal of Pharmacy and Pharmacology

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Objectives Direct scavenging of reactive oxygen species could not prevent ER stress-associated cytotoxicity of indomethacin or diclofenac in Caco-2 cells. This study investigated the effects of three polyphenolic antioxidants epigallocatechin gallate (EGCG), phyllanthin and hypophyllathin in non-steroidal anti-inflammatory drug-induced Caco-2 apoptosis. Methods Cells were treated with ER stressors (indomethacin, diclofenac, tunicamycin or thapsigargin) and the polyphenols for up to 72 h. Cell viability, apoptosis and mitochondrial function were monitored by MTT, Hoechst 33342 and TMRE assays, respectively. Protein expression was measured by Western blot analysis. Key findings Epigallocatechin gallate suppressed increases in p-PERK/p-eIF-2a/ ATF-4/CHOP and p-IRE-1a/p-JNK1/2 expression levels in the cells treated with any of the ER stressors, leading to inhibition of apoptosis. In contrast, phyllanthin increased apoptosis in the cells subsequently exposed to either diclofenac, tunicamycin or thapsigargin, but not in the indomethacin-treated cells. The potentiation effect of phyllanthin seen with the three ER stressors was related to suppression of survival p-Nrf-2/HO-1 expression, resulting in increased activation of the eIF-2a/ATF-4/CHOP pathway. On the other hand, hypophyllanthin had no significant effect on the ER stressor-induced apoptosis. Conclusion Epigallocatechin gallate, phyllanthin and hypophyllanthin displayed different effects in the ER stress-mediated apoptosis, depending upon their interaction with the specific unfolded protein response signalling.

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“…Simultaneously EGCG inhibited neuronal apoptosis with reducing ER abnormal ultrastructural swelling and downregulating ERS-associated proteins in APP/PS1 transgenic mice. In conclusion, EGCG decreased the neurotoxicity via decreasing ERS related apoptosis in the AD [ 103 , 104 ]. In transient focal cerebral ischemia rat models, EGCG treatment after ischemia inhibited ERS with decreasing the expression of glucose-regulated caspase-12, CHOP, and GRP78, and improved the neurological status via inhibiting TRPC6 proteolysis and activating CREB in the MEK/ERK pathway [ 105 ].…”

Section: The Role Of Egcg In Ers-induced Apoptosis and Human Diseasesmentioning

confidence: 99%

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseases

2020

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Epigallocatechin Gallate Reduces Amyloid β‐Induced Neurotoxicity via Inhibiting Endoplasmic Reticulum Stress‐Mediated Apoptosis

Cited by 54 publications

References 44 publications

Protective Effects of Some Grapevine Polyphenols against Naturally Occurring Neuronal Death

Protective Effects of Some Grapevine Polyphenols against Naturally Occurring Neuronal Death

Modulation of non-steroidal anti-inflammatory drug-induced, ER stress-mediated apoptosis in Caco-2 cells by different polyphenolic antioxidants: a mechanistic study

The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseases

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