In this review, the anti-infective effects of EGCG against viruses, bacteria and different fungi were summarized and discussed. A comparison of the antiviral activity of EGCG (Table 1) shows that the RNA and DNA viruses of various families with different replication strategies are affected by the green tea molecule. The underlying mechanisms by which different viruses were inhibited by EGCG are relatively diverse and in some cases not known. However, for most of the enveloped viruses, like HCV, HIV, HSV and influenza, ECGC has been shown to alter or damage the virus particles and so prevent viral entry. Therefore, it is hypothesized that the primary target of EGCG is the viral membrane while the host cell membrane appears to be unaffected. Other catechins do not have such a strong ability to bind to viral membranes. In analogy to viruses, the main underlying mechanism for the EGCG-induced inhibition of growth and killing of bacteria is disruption the lipid layers of the bacterial cell wall. In addition, for gram-negative bacteria and fungi it was demonstrated that EGCG is an efficient inhibitor of dihydrofolate reductase resulting in blocking of the folic acid metabolism.
A crucial aspect in the anti-infective effects of EGCG is the translation into clinically relevant strategies. In this regard, poor membrane permeability, low chemical stability and rapid metabolism of EGCG pose substantial obstacles that need to be addressed by future studies and possible derivatives of the EGCG backbone. Moreover, testing the safety and tolerability of a drug are very important issues before approval for clinical use. In studies with healthy human volunteers, it was shown that EGCG is safe and well-tolerated at oral doses of 800 mg EGCG day-1 over a time period of 4 weeks, which is equivalent to about 8–16 cups of green tea a day (Chow et al., 2003). The plasma concentration ranged from 0.13 to 3.4 μg mL−1, which reaches the IC50 of EGCG that was determined, for example, for HCV (Ciesek et al., 2011; Calland et al., 2012), but would probably not be high enough to eliminate the virus completely. In another study the safety, tolerability and pharmacokinetic properties of single-dose administration of EGCG that ranged from 50 to 1600 mg were analysed (Table 3) (Ullmann et al., 2003). EGCG peak concentrations were reached between 1.3–2.2 h. The plasma kinetics of EGCG were assessed at intervals for a time frame of 26 h after administration. The mean total EGCG area under the concentration–time curve from 0 h to infinity AUC(0-∞) ranged from 442 to 10 368 ng h mL−1 and the mean terminal elimination half-life t1/2z were seen from 1.9 to 4.6 h. Importantly, doses of purified EGCG up to 1600 mg are generally well tolerated (Ullmann et al., 2003).
In addition, recent attempts have been made to try and enhance the activity of EGCG. For example, the bioavailability of chronic administration of EGCG 800 mg can be increased by peracetylation (Lambert et al., 2006). Acylation enhances the anti-influenza virus activity of EGCG by up to 44-fold (Mori et al., 2008). Furthermore, addition of long alkyl chains to EGCG significantly enhanced its in vitro activity against several bacteria and fungi, particularly against S. aureus including MRSA (Matsumoto et al., 2012). Recently, the first controlled human studies with EGCG have been reported. A prospective randomized controlled study evaluated the effects of tea catechin inhalation on eradication of MRSA in sputum of disabled elderly patients (Yamada et al., 2006). Inhalation of 2 mL tea catechin extract solution (43% of catechins are composed of EGCG) three times daily for 7 days led to the disappearance of MRSA in the sputum of 31% of the patients in comparison with 12% in the control group (saline). But this difference was not statistically significant (P = 0.091). However, no adverse events of nebulized EGCG were observed during the study. In the case of influenza viruses, a randomized, placebo-controlled trial was conducted showing that consuming catechins for 5 months has a statistically significant preventive effect on clinically defined influenza infections (Matsumoto et al., 2012), but further large-scale trials are needed to confirm these findings.
Interestingly, the therapeutic effects of a mixture of at least five different catechins, polyphenon E, where EGCG is the most abundant component (Clark and You, 2006) is commonly used clinically. This well-defined pharmaceutical mixture is a botanical drug approved by Food and Drug Administration (FDA) and European Medicines Agency (EMEA) as a topical treatment of external genital and anal warts in adults. It is the first prescription botanical (herbal) drug approved by FDA under the ‘new’ drug amendments of 1962 that required drugs to be proven both safe and effective prior to being marketed in the USA. External genital warts, caused by human papilloma viruses (HPV type 6 or 11), are one of the most common and fastest-spreading venereal diseases worldwide.
In conclusion, the magnitude of EGCG's anti-infective activity differs substantially between different reports probably due to different experimental setups and in vitro systems. Most of the data come from in vitro studies and future research efforts should focus on the design of animal models for investigating the anti-pathogenic effects of teas and tea ingredients. In addition, extraction procedure and methods of in vitro testing should be standardized to allow better comparison and interpretation of results. There is still a long way to go and future work is needed before EGCG can be routinely administered as an anti-infective drug in patients. However, the exciting findings of the past years should stimulate further research on EGCG that ultimately may translate into future therapeutic applications of EGCG and/or related catechins.
Зеленый чай: перспективный натуральный продукт для здоровья полости рта.
Зеленый чай является ведущим напитков на Дальнем Востоке в течение тысяч лет; она рассматривается долгое время в качестве оздоровительного продукта. Зеленый чай является важным источником полифенольных антиоксидантов. Полифенолы, в том числе эпигаллокатехин 3 галлат (EGCG) составят для Вас наиболее интересное компонентов в зеленых листьях чая. Зеленый чай обладает потенциалом для защиты от различных злокачественных, сердечно-сосудистых и метаболических заболеваний. Растет объем доказательств, указывающих благотворную роль зеленого чая и его полифенолы в полости рта. Зеленый чай защищает от бактериальных индуцированной кариеса. Полифенолы чая обладают противовирусными свойствами, как полагают, чтобы помочь в защите от вируса гриппа. Кроме того, полифенолы зеленого чая могут отменить неприятного запаха изо рта через модификация отдушка сернистых компонентов. Полости рта окислительного стресса и воспаления, вследствие курения сигарет и сигареты' вредных соединений, никотина и акролеин, может быть снижена в присутствии полифенолы зеленого чая. Как правило, зеленый чай защищает здоровые клетки от злокачественного перерождения и локально обладает способностью индуцировать апоптоз в устной раковые клетки. Все вместе, растет интерес к польза для здоровья зеленого чая в области здоровья полости рта. Тем не менее, все еще существует необходимость проведения дополнительных клинических и биологических исследований, рекомендации по зеленый чай потребление как часть профилактики и лечения конкретных патологий ротовой.
Arch Oral Biol. 2012 May;57(5):429-35. doi: 10.1016/j.archoralbio.2011.11.017. Epub 2012 Jan 5.