Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age
Abstract
:1. Introduction
2. Neurodegeneration: Examination of Two Prevalent Neuroregressive Disorders
2.1. Parkinson’s Disease (PD)
2.2. Alzheimer’s Disease (AD)
2.3. Protein Aggregation in AD: The Role of Amyloid Beta (Aβ)
2.4. Tau Protein: Neurofibrillary Tangles and Aggregation in AD
3. Role of Inflammation
3.1. Microglia and the Debilitating Effects Caused by Aging
3.2. Microglia and Tau
4. Neuroinflammatory Mediators
4.1. Oxidative Stress
4.2. Nitric Oxide
4.3. Autophagy
5. Inflammatory Signaling Pathways Involved in Neurodegeneration
6. Contributing Determinants to the Incidence of AD: Health Disparities, Sex, and Gender
7. Preventive Measures for Neurodegenerative Disease: Nutraceutical and Phytochemical Use in Neurodegenerative Disease
Green Tea and Its Derivatives: Therapeutic Actions Related to Inflammation and Neurodegeneration
8. EGCG Synthesis, Structure, and Therapeutic Action
EGCG Bioavailability and Modifications
9. Epigallocatechin-3-Gallate (EGCG) Therapeutic Action in AD and PD
10. Autophagic Role of EGCG
11. Other EGCG Therapeutic Applications for Neuroinflammation and Neurorescue in Other Related Pathological Disorders
Role of microRNA (miRNA) in AD: Medicinal Action by EGCG
12. EGCG in Clinical Studies of AD and PD
13. Lipids, Cholesterol Metabolism, and AD: A New Possibility for EGCG?
14. Future Directions
15. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pharmacological Action | Model (In Vivo/In Vitro) | Therapeutic Focus | Reference |
---|---|---|---|
Anti-inflammatory | In vivo transgenic mice, human volunteers, Elegans, hamsters, Drosophila | A review of the role of green tea (Camellia sinensis) in antiphotoaging, stress resistance, neuroprotection, and autophagy | [161] |
In vitro and in vivo airway epithelial cells, experimental autoimmune encephalomyelitis (EAE), rat aortas, RA human patients, human umbilical vein endothelial cells, and synovial fibroblasts | The prevention and treatment of vascular inflammation in rheumatoid arthritis | [185] | |
In vivo: human | Molecular pharmacology of inflammation: medicinal plants as anti-inflammatory agents | [170] | |
In vitro: adult human ventricular cardiomyocyte cell line AC16 | Suppresses cigarette smoking-induced inflammation in human cardiomyocytes, utilizing ROS-mediated MAPK and NF-κB pathways | [171] | |
In vivo: Wistar albino female rats | Attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model | [175] | |
In vivo: Human mast cell line | Blockade of RANKL/RANK signaling pathway by EGCG alleviates mast cell-mediated inflammatory reactions | [174] | |
Antioxidant/oxidative stress | In vitro: human bronchial epithelial cells | Diminishes cigarette smoke-induced oxidative stress, lipid peroxidation, and inflammation in human bronchial epithelial cells | [172] |
In vitro: Single ventricular myocytes | Protective effects against lead-induced oxidative damage | [177] | |
In vivo: Adult male Wistar albino rats | Attenuates cadmium-induced chronic renal injury and fibrosis | [179] | |
multiple human and cell model systems | EGCG Management of Heavy Metal-Induced Oxidative Stress: Mechanisms of Action, Efficacy, and Concerns | [149] | |
In vitro BEAS-2B cells and EBV-BL cells | Protects against chromate-induced toxicity in vitro | [178] | |
In vivo Male 14-day-old Wistar rats | Protects rat brain mitochondria against cadmium-induced damage | [176] | |
Amyloid-beta formation inhibition | In vivo human adult brain | Microglial dysfunction in brain aging and Alzheimer’s disease | [65] |
In vitro N2a-APP695 cells | EGCG attenuates β-amyloid generation and oxidative stress involvement of PPARγ | [196] | |
In vitro and in vivo Human embryonic kidney cells human CNS-derived neuroblastoma cells, APPHEK293 and SwAPP-N2a cells. Biomarkers of CSF, plasma, blood-derived brain exosomes, monocytes, and peripheral blood mononuclear cells | Autophagy modulation as a treatment of amyloid diseases | [197] | |
In vitro hippocampal neurons, mouse, rat brain cells, and yeast model overexpressing htt | EGCG Amyloid Aggregation and Neurodegenerative Diseases | [158] | |
In vivo mixed POPC/POPG (7:3) lipid bilayer | Plays a dual role in Aβ 42 protofibril disruption and membrane protection: A dynamic molecular study | [198] | |
In vitro Synthetic Aβ42, Aβ fibril formulation | The effect of (−)-epigallocatechin-3-gallate on the amyloid-β secondary structure | [199] | |
Autophagy | In vitro C3H10T1/2 cells and 3T3-L1 preadipocytes | Effects of EGCG on autophagic lipolysis in adipocytes | [166] |
In vitro HEPG2 cells | A new molecular mechanism underlying the EGCG mediated autophagic modulation of AFP | [147] | |
Human endothelial cells | Protects vascular endothelial cells from oxidative stress induced damage by targeting the autophagy dependent PI3K-Akt-mTOR pathway | [167] | |
HEK293T cells | Promotes autophagy dependent survival via influencing the balance of mTOR -AMPK pathways upon endoplasmic reticulum stress | [168] | |
Cholesterol/Lipid Metabolism | high-fat diet induced mouse obesity model, human volunteers, rats, | The beneficial effects of principal polyphenols from green tea, coffee, wine, and curry on obesity | [37] |
BV2 cells and Twenty-four-week-old male C57BL/6J mice | Attenuates neuroinflammation in palmitic acid-stimulated bv-2 microglia and high-fat diet-induced obese mice | [200] | |
C57BL/6 mice | prevents inflammation and diabetes -induced glucose tolerance through inhibition of NLRP3 inflammasome activation | [201] | |
broiler chickens | Effects of EGCG on lipid metabolism and its underlying molecular mechanism | [202] | |
Anti-Aging | SH-SY5Y cells, SAMP10, and ddy mice | A review of the role of green tea (Camellia sinensis) in antiphotoaging, stress resistance, neuroprotection, and autophagy | [161] |
36 weeks old, spontaneously hypertensive rats and male normotensive Wistar-Kyoto rats | Green tea suppresses brain aging | [203] | |
3T3-L1 preadipocytes | Cerebral cortex apoptosis in early aged hypertension: effects of epigallocatechin-3-gallate | [204] | |
Wistar albino rats | Suppresses premature senescence of preadipocytes by inhibition of PI3K/Akt/mTOR pathway and induces senescent cell death by regulation of Bax/Bcl-2 pathway | [205] | |
MicroRNA | APP/PS1 transgenic mouse model | Identification of circulating mir-125b as a potential biomarker of Alzheimer’s disease | [193] |
chondrocytes, human THP-1 monocytic cells, and primary human fibroblasts | Quercetin, epigallocatechin gallate, curcumin, and resveratrol: from dietary sources to human microrna modulation | [192] | |
Sprague Dawley Rats, chondrocytes, monocytes, and mice | Targeting miRNAs by polyphenols: a novel therapeutic strategy for aging | [191] |
Study Identifier | Study Type | Study Population | Study Purpose | Study Participants | Number of Patients Recruited | Intervention | Status |
---|---|---|---|---|---|---|---|
NCT03978052 | Interventional | Spain | Prevention of cognitive decline in ApoE4 carriers with subjective cognitive decline after EGCG and a multimodal intervention | Alzheimer’s Disease cognitive function nutritional intervention | 200 | Dietary Supplement: EGCG, Placebo EGCG, personalized intervention, and lifestyle recommendations | Recruiting |
NCT00951834 | Interventional | Germany | Sunphenon EGCg (Epigallocatechin-Gallate) in the early stage of Alzheimer’s disease | Alzheimer’s Disease | 21 | Drug: Epigallocatechin-Gallate Drug Placebo | Completed |
NCT00461942 | Interventional | China | Efficacy and safety of green tea polyphenol in de novo Parkinson’s disease patients | Parkinson’s Disease | 480 | Drug: Green Tea Polyphenols (EGCG/ECG) | Completed |
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Payne, A.; Nahashon, S.; Taka, E.; Adinew, G.M.; Soliman, K.F.A. Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age. Biomolecules 2022, 12, 371. https://doi.org/10.3390/biom12030371
Payne A, Nahashon S, Taka E, Adinew GM, Soliman KFA. Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age. Biomolecules. 2022; 12(3):371. https://doi.org/10.3390/biom12030371
Chicago/Turabian StylePayne, Ashley, Samuel Nahashon, Equar Taka, Getinet M. Adinew, and Karam F. A. Soliman. 2022. "Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age" Biomolecules 12, no. 3: 371. https://doi.org/10.3390/biom12030371