The main green tea polyphenol epigallocatechin-3-gallate counteracts semen-mediated enhancement of HIV infection.

Peptide fragments, derived from prostatic acidic phosphatase, are secreted in large amounts into human semen and form amyloid fibrils. These fibrillar structures, termed semen-derived enhancer of virus infection (SEVI), capture HIV virions and direct them to target cells. Thus, SEVI appears to be an important infectivity factor of HIV during sexual transmission. Here, we are able to demonstrate that epigallocatechin-3-gallate (EGCG), the major active constituent of green tea, targets SEVI for degradation. Furthermore, it is shown that EGCG inhibits SEVI activity and abrogates semen-mediated enhancement of HIV-1 infection in the absence of cellular toxicity. Therefore, EGCG appears to be a promising supplement to antiretroviral microbicides to reduce sexual transmission of HIV-1.

Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises?

Epigallocatechin-3-gallate (EGCG), the main and most significant polyphenol in green tea, has shown numerous health promoting effects acting through different pathways, as antioxidant, anti-inflammatory and anti-atherogenic agent, showing gene expression activity, functioning through growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, the ubiquitin/proteasome degradation pathway, as well as eliciting an amyloid protein remodeling activity. However, epidemiological inferences are sometimes conflicting and in vitro and in vivo studies may seem discrepant. Current knowledge on how to enhance bioavailability could be the answer to some of these issues. Furthermore, dose levels, administration frequency and potential side effects remain to be examined.

670 nm laser light and EGCG complementarily reduce amyloid-ß aggregates in human neuroblastoma cells: basis for treatment of Alzheimer's disease?

OBJECTIVE: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer's disease (AD). BACKGROUND DATA: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra- and intracellular deposition of amyloid-beta (Aß) fibrils in the brain. Recently, it was shown that extracellular Aß can enter brain cells, resulting in neurotoxicity. METHODS: After internalization of Aß(42) into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm(-2)) and/or treated with epigallocatechin gallate (EGCG). RESULTS: In irradiated cells, Aß(42) aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCG-treated cells, Aß(42) aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with Aß(42) and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in Aß(42)-free cells, when compared to nonirradiated cells. Laser-induced clearance of Aß(42) aggregates occurred at the expense of cellular ATP. CONCLUSIONS: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Aß aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD.

Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis.

BACKGROUND: Amyloid light chain (AL) amyloidosis is a rare disease with poor prognosis and limited therapeutic alternatives. Recently, one clinical case with cardiac involvement, as well as a compelling evidence of green tea polyphenol, epigallocatechin-3-gallate (EGCG), inducing the formation of benign aggregation products that do not polymerize into fibrils were published. This is a report of the cardiac effects of green tea consumption in these patients. METHODS: Patients with known cardiac involvement in AL amyloidosis were examined by routine cardiovascular examinations that took place every 3-6 months. Of 59 patients with cardiac involvement, 11 revealed a decrease of at least 2 mm of interventricular wall thickness, after initiation of regular green tea consumption (GT). A matched historic control group (n = 22) was selected. Comprehensive echocardiography was conducted at every control examination and analyzed offline by two independent examiners. RESULTS: GT patients showed an improvement in New York Heart Association (NYHA) class from a median of 3 (25th, 75th percentiles: 2, 3) to 2 (2, 3), P = 0.038. Septal thickness decreased from 18 (18, 20) to 16 (16, 17) mm, P = 0.021. Left ventricular mass index decreased from 175 (154, 180) to 133 (128, 154) g/m(2), P = 0.007. Comparing both groups, an increase in left ventricular ejection fraction could be found in the GT group, 65 (51, 73) versus 53 (47, 59)%, P = 0.012. These changes could not be observed in the control group. CONCLUSION: Consumption of green tea polyphenol EGCG in patients with cardiac involvement with AL amyloidosis causes a significant decrease in left ventricular wall thickness and mass, as well as an improvement in NYHA functional classification and left ventricular ejection fraction.

p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias.

Conventional cytogenetic analysis in B-cell chronic lymphocytic leukemia (B-CLL) has been very difficult, and the prognostic significance of specific chromosome aberrations is under discussion. Recent improvements in fluorescence in situ hybridization (ISH) techniques have provided an alternative approach for the detection of chromosome aberrations. Here, an interphase cytogenetic study was performed to analyze the incidence and prognostic significance of a p53 gene deletion in B-CLL and related disorders. We studied mononuclear cells from 100 patients with chronic B-cell leukemias [B-CLL, 90 patients; B-prolymphocytic leukemia (B-PLL), 7; Waldenström's macroglobulinemia (WM), 3] by fluorescence ISH with a genomic p53 DNA probe. In a subset of patients, additional G-banding analysis and single strand conformation polymorphism (SSCP) analysis was performed. Seventeen of the 100 patients [17%; B-CLL, 11 of 90 (12%); WM, 1 of 3; B-PLL, 5 of 7] exhibited a monoallelic p53 gene deletion by ISH. G-banding analysis demonstrated abnormalities of chromosome 17 in 13 of these 17 patients, all leading to loss of band 17p13. SSCP analysis showed aberrant bands in 9 of 14 patients with a p53 gene deletion. None of 12 patients with a p53 gene deletion compared with 20 of 36 patients (56%) without a deletion responded to therapy with fludarabine or pentostatin (P < .001). The difference in survival probabilities from the time of diagnosis and from the start of treatment with purine analogs between the two groups was highly significant (P < .001). In multivariate analysis, p53 gene deletion was the strongest prognostic factor for survival. In conclusion, p53 gene deletion predicts for non-response to therapy with purine analogs and for poor survival in chronic B-cell leukemias.