Epigallocatechin-3-gallate (EGCG) for Clinical Trials: More Pitfalls than Promises?

Mereles, Derliz; Hünstein, W.

doi:10.3390/ijms12095592

Cited by 271 publications

(227 citation statements)

References 45 publications

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“…Plasma concentrations close to 1 μM were achieved in mice after oral administration of EGCG (75 mg/kg) [105]. Oral administration of EGCG (450 mg) or green tea extract (1.2-4.5 g, corresponding to 100-300 mg EGCG) resulted in similar peak plasma concentrations in humans [106][107][108]. While EGCG has been recognized to be hepatotoxic in mice at concentrations of 500 mg/kg body weight and above and sporadic incidents of hepatotoxicity in humans have been reported [109,110], daily doses of 800 mg EGCG have been used in clinical trials without adverse effects (clinical trial NCT00951834) [111].…”

Section: Perspectives For Prevention and Therapymentioning

confidence: 99%

“…However, a widely recognized problem in the therapeutic application of EGCG is the large variability in the bioavailability of orally administered EGCG (reviewed in [108] and [112]). This is owing to its high sensitivity to oxidation, the tendency to conjugate to proteins in the digestive tract (e.g., casein), and rapid metabolism in the body.…”

Section: Perspectives For Prevention and Therapymentioning

confidence: 99%

“…With an especially conscientious oral regimen these problems can be overcome [76]. However, the variations in bioavailability confound the systematic evaluation of treatment outcome in clinical studies [108]. In addition, only 10-20% of the EGCG passes through the blood-brain barrier [113].…”

Section: Perspectives For Prevention and Therapymentioning

confidence: 99%

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Natural Compounds May Open New Routes to Treatment of Amyloid Diseases

Bieschke

2013

Neurotherapeutics

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Protein misfolding disorders, such as Alzheimer's disease and Parkinson's disease, have in common that a protein accumulates in an insoluble form in the affected tissue. The process of aggregation follows a mechanism of seeded polymerization. Although the toxic species is still not well defined, the process, rather than the end product, of fibril formation is likely the main culprit in amyloid toxicity. These findings suggest that therapeutic strategies directed against the protein misfolding cascade should focus on depleting aggregation intermediates rather than on large fibrillar aggregates. Recent studies involving natural compounds have suggested new intervention strategies. The polyphenol epi-gallocatechine-3-gallate (EGCG), the main polyphenol in Camilla sinensis, binds directly to a large number of proteins that are involved in protein misfolding diseases and inhibits their fibrillization. Instead, it promotes the formation of stable, spherical aggregates. These spherical aggregates are not cytotoxic, have a lower β-sheet content than fibrils, and do not catalyze fibril formation. Correspondingly, epi-gallocatechine-3-gallate remodels amyloid fibrils into aggregates with the same properties. Derivatives of Orcein, which is a phenoxazine dye that can be isolated from the lichen Roccella tinctoria, form a second promising class of natural compounds. They accelerate fibril formation of the Alzheimer's disease-related amyloid-beta peptide. At the same time these compounds deplete oligomeric and protofibrillar forms of the peptide. These compounds may serve as proof-of-principle for the strategies of promoting and redirecting fibril formation. Both may emerge as two promising new therapeutic approaches to intervening into protein misfolding processes.

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Section: Perspectives For Prevention and Therapymentioning

confidence: 99%

Section: Perspectives For Prevention and Therapymentioning

confidence: 99%

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Natural Compounds May Open New Routes to Treatment of Amyloid Diseases

Bieschke

2013

Neurotherapeutics

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“…In another study green tea extract administration was found to be effective in enhancing learning and memory in aged rats, and also demonstrated selectivity for inhibition of AChE [82]. In recent years, green tea has been explored in clinical trials relating to learning and memory-related disorders, indicating its potential for improving learning and memory [83]. In a randomized, double-blind, placebo-controlled study, a combination of green tea extract and L-theanine (LGNC-07) showed potential cognitive improvement in patients with MCI [84].…”

Section: Green Teamentioning

confidence: 99%

Traditional Korean East Asian Medicines and Herbal Formulations for Cognitive Impairment

Kumar

Song

et al. 2013

Molecules

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Abstract:Hanbang, the Traditional Korean Medicine (TKM), is an inseparable component of Korean culture both within the country, and further afield. Korean traditional herbs have been used medicinally to treat sickness and injury for thousands of years. Oriental medicine reflects our ancestor's wisdom and experience, and as the elderly population in Korea is rapidly increasing, so is the importance of their health problems. The proportion of the population who are over 65 years of age is expected to increase to 24.3% by 2031. Cognitive impairment is common with increasing age, and efforts are made to retain and restore the cognition ability of the elderly. Herbal materials have been considered for this purpose because of their low adverse effects and their cognitive-enhancing or anti-dementia activities. Herbal materials are reported to contain several active compounds that have effects on cognitive function. Here, we enumerate evidence linking TKMs which have shown benefits in memory improvements. Moreover, we have also listed Korean herbal formulations which have been the subject of scientific reports relating to memory improvement.

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“…Methylation decreases the hydrophilicity of catecholic compounds; further sulfation/glucuronidation of the methylated product is usually needed for the elimination of the product from the body. 11,12 There has been discussion that level of methylation is influenced by polymorphisms of catechol-Omethyltransferase, but the effect of this has not yet been fully studied. Within the plasma, serum albumin contributes to transport and stabilization by directly preventing EGCG oxidation.…”

Section: Introductionmentioning

confidence: 99%