Epigallocatechin-3-gallate (EGCG), an active compound of green tea and its role in diseases cure and prevention has been proven. Its role in diseases management can be attributed to its antioxidant ...and anti-inflammatory properties. The anti-cancer role of this green tea compound has been confirmed in various types of cancer and is still being under explored. EGCG has been proven to possess a chemopreventive effect through inhibition of carcinogenesis process such as initiation, promotion, and progression. In addition, this catechin has proven its role in cancer management through modulating various cell signaling pathways such as regulating proliferation, apoptosis, angiogenesis and killing of various types of cancer cells. The additive or synergistic effect of epigallocatechin with chemopreventive agents has been verified as it reduces the toxicities and enhances the anti-cancerous effects. Despite its effectiveness and safety, the implications of EGCG in cancer prevention is certainly still discussed due to a poor bioavailability. Several studies have shown the ability to overcome poor bioavailability through nanotechnology-based strategies such as encapsulation, liposome, micelles, nanoparticles and various other formulation. In this review, we encapsulate therapeutic implication of EGCG in cancer management and the mechanisms of action are discussed with an emphasis on human clinical trials.
Scope
To understand the mechanism by which green tea lowers the risk of dementia, focus was placed on the metabolites of epigallocatechin gallate (EGCG), the most abundant catechin in green tea. Much ...of orally ingested EGCG is hydrolyzed to epigallocatechin (EGC) and gallic acid. In rats, EGC is then metabolized mainly to 5‐(3′,5′‐dihydroxyphenyl)‐γ‐valerolactone (EGC‐M5) and its conjugated forms, which are distributed to various tissues. Therefore, we examined the permeability of these metabolites into the blood–brain barrier (BBB) and nerve cell proliferation/differentiation in vitro.
Methods and Results
The permeability of EGC‐M5, glucuronide, and the sulfate of EGC‐M5, pyrogallol, as well as its glucuronide into the BBB were examined using a BBB model kit. Each brain‐ and blood‐side sample was subjected to liquid chromatography tandem‐mass spectrometry analysis. BBB permeability (%, in 0.5 h) was 1.9–3.7%. In human neuroblastoma SH‐SY5Y cells, neurite length was significantly prolonged by EGC‐M5, and the number of neurites was increased significantly by all metabolites examined.
Conclusion
The permeability of EGC‐M5 and its conjugated forms into the BBB suggests that they reached the brain parenchyma. In addition, the ability of EGC‐M5 to affect nerve cell proliferation and neuritogenesis suggests that EGC‐M5 may promote neurogenesis in the brain.
To understand the mechanism by which green tea lowers the risk of dementia, metabolites of epigallocatechin gallate (EGCG) are focused on. The in vitro blood–brain barrier permeability of 5‐(3′,5′‐dihydroxyphenyl)‐γ‐valerolactone (EGC‐M5) is 3.7% in 0.5 h. The neuritogenesis of SH‐SY5Y cells is enhanced by EGC‐M5. The metabolite of EGCG, EGC‐M5, may promote neurogenesis in the brain.
Alzheimer's disease (AD) is characterised by the apoptosis of cholinergic neurons and the consequent attenuation of acetylcholine mediated neurotransmission, resulting in neurodegeneration. ...Acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE) are attractive therapeutic targets in the treatment of AD since inhibition of these enzymes can be used to restore synaptic concentrations of acetylcholine. Whilst inhibitors for these enzymes such as galantamine and rivastigmine have been approved for use, none are able to halt the progression of AD and are responsible for the production of troublesome side-effects. Efficacious cholinesterase inhibitors have been isolated from natural plant-based compounds with many demonstrating additional benefits beyond cholinesterase inhibition, such as antioxidation and anti-inflammation, which are key parts of AD pathology. In this study, five natural flavan-3-ol (catechin) compounds: ((-)-epicatechin (EC), catechin, (-)-epicatechin-3-gallate (ECG),) (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), isolated from green tea, were screened for their cholinesterase inhibitory activity using the Ellman assay. The kinetics of inhibition was determined using reciprocal Lineweaver-Burk plots. EGCG was the only compound found to produce statistically significant, competitive inhibition, of both AChE (
< 0.01) and BuChE (
< 0.01) with IC50 values of 0.0148 µmol/mL and 0.0251 µmol/mL respectively. These results, combined with previously identified antioxidative and anti-inflammatory properties, highlight the potential use of EGCG in the treatment of AD, provided it can be delivered to cholinergic neurons in therapeutic concentrations. Further testing of EGCG in vivo is recommended to fully characterise the pharmacokinetic properties, optimal method of administration and efficacy of this novel plant-based compound.
Catechins are natural polyphenolic phytochemicals that exist in food and medicinal plants, such as tea, legume and rubiaceae. An increasing number of studies have associated the intake of ...catechins-rich foods with the prevention and treatment of chronic diseases in humans, such as inflammatory bowel disease (IBD). Some studies have demonstrated that catechins could significantly inhibit the excessive oxidative stress through direct or indirect antioxidant effects and promote the activation of the antioxidative substances such as glutathione peroxidases (GPO) and glutathione (GSH), reducing the oxidative damages to the colon. In addition, catechins can also regulate the infiltration and proliferation of immune related-cells, such as neutrophils, colonic epithelial cells, macrophages, and T lymphocytes, helping reduce the inflammatory relations and provide benefits to IBD. Perhaps catechins can further inhibit the deterioration of intestinal lesions through regulating the cell gap junctions. Furthermore, catechins can exert their significant anti-inflammatory properties by regulating the activation or deactivation of inflammation-related oxidative stress-related cell signaling pathways, such as nuclear factor-kappa B (NF-κB), mitogen activated protein kinases (MAPKs), transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), signal transducer and the activator of transcription 1/3 (STAT1/3) pathways. Finally, catechins can also stabilize the structure of the gastrointestinal micro-ecological environment via promoting the proliferation of beneficial intestinal bacteria and regulating the balance of intestinal flora, so as to relieve the IBD. Furthermore, catechins may regulate the tight junctions (TJ) in the epithelium. This paper elaborates the currently known possible molecular mechanisms of catechins in favor of IBD.
An expanding body of preclinical evidence suggests EGCG, the major catechin found in green tea (Camellia sinensis), has the potential to impact a variety of human diseases. Apparently, EGCG functions ...as a powerful antioxidant, preventing oxidative damage in healthy cells, but also as an antiangiogenic and antitumor agent and as a modulator of tumor cell response to chemotherapy. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing oncogenic transcription factors and pluripotency maintain factors. In vitro studies have demonstrated that EGCG blocks carcinogenesis by affecting a wide array of signal transduction pathways including JAK/STAT, MAPK, PI3K/AKT, Wnt and Notch. EGCG stimulates telomere fragmentation through inhibiting telomerase activity. Various clinical studies have revealed that treatment by EGCG inhibits tumor incidence and multiplicity in different organ sites such as liver, stomach, skin, lung, mammary gland and colon. Recent work demonstrated that EGCG reduced DNMTs, proteases, and DHFR activities, which would affect transcription of TSGs and protein synthesis. EGCG has great potential in cancer prevention because of its safety, low cost and bioavailability. In this review, we discuss its cancer preventive properties and its mechanism of action at numerous points regulating cancer cell growth, survival, angiogenesis and metastasis. Therefore, non-toxic natural agent could be useful either alone or in combination with conventional therapeutics for the prevention of tumor progression and/or treatment of human malignancies.
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Epigallocatechin gallate (EGCG) is a flavonoid belonging to the chemical class of falvan-3-ols (catechins) esterified with gallic acid. It is the main catechin found in green tea ...(Camellia sinensis L.) accounting for about 50% of its total polyphenols. Extensive research performed in recent years has revealed that green tea demonstrates a wide range of positive biological activities against serious chronic diseases such as cardiovascular and neurodegenerative pathologies, cancer, metabolic syndrome and type 2 diabetes. These protective properties can be traced back to the potent antioxidant and anti-inflammatory activities of EGCG. Recent studies have suggested that it may exert its beneficial effects by modulating mitochondrial functions impacting mitochondrial biogenesis, bioenergetic control (ATP production and anabolism), alteration of the cell cycle, and mitochondria-related apoptosis. This review evaluates recent evidence on the ability of EGCG to exert critical influence on the above mentioned pathways.
Protein misfolding and/or aggregation has been implicated as the cause of several human diseases, such as Alzheimer’s and Parkinson’s diseases and familial amyloid polyneuropathy. These maladies are ...referred to as amyloid diseases, named after the cross-β-sheet amyloid fibril aggregates or deposits common to these disorders. Epigallocatechin-3-gallate (EGCG), the principal polyphenol present in green tea, has been shown to be effective at preventing aggregation and is able to remodel amyloid fibrils comprising different amyloidogenic proteins, although the mechanistic underpinnings are unclear. Herein, we work toward an understanding of the molecular mechanism(s) by which EGCG remodels mature amyloid fibrils made up of Aβ1–40, IAPP8–24, or Sup35NM7–16. We show that EGCG amyloid remodeling activity in vitro is dependent on auto-oxidation of the EGCG. Oxidized and unoxidized EGCG binds to amyloid fibrils, preventing the binding of thioflavin T. This engagement of the hydrophobic binding sites in Aβ1–40, IAPP8–24, or Sup35NMAc7–16 Y→F amyloid fibrils seems to be sufficient to explain the majority of the amyloid remodeling observed by EGCG treatment, although how EGCG oxidation drives remodeling remains unclear. Oxidized EGCG molecules react with free amines within the amyloid fibril through the formation of Schiff bases, cross-linking the fibrils, which may prevent dissociation and toxicity, but these aberrant post-translational modifications do not appear to be the major driving force for amyloid remodeling by EGCG treatment. These insights into the molecular mechanism of action of EGCG provide boundary conditions for exploring amyloid remodeling in more detail.
Beneficial Properties of Green Tea Catechins Musial, Claudia; Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena
International journal of molecular sciences,
03/2020, Volume:
21, Issue:
5
Journal Article
Peer reviewed
Open access
Green tea (
) is widely known for its anticancer and anti-inflammatory properties. Among the biologically active compounds contained in
, the main antioxidant agents are catechins. Recent scientific ...research indicates that the number of hydroxyl groups and the presence of characteristic structural groups have a major impact on the antioxidant activity of catechins. The best source of these compounds is unfermented green tea. Depending on the type and origin of green tea leaves, their antioxidant properties may be uneven. Catechins exhibit the strong property of neutralizing reactive oxygen and nitrogen species. The group of green tea catechin derivatives includes: epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate. The last of these presents the most potent anti-inflammatory and anticancer potential. Notably, green tea catechins are widely described to be efficient in the prevention of lung cancer, breast cancer, esophageal cancer, stomach cancer, liver cancer and prostate cancer. The current review aims to summarize the potential anticancer effects and molecular signaling pathways of major green tea catechins. It needs to be clearly emphasized that green tea as well as green tea catechols cannot replace the standard chemotherapy. Nonetheless, their beneficial effects may support the standard anticancer approach.
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