Skin and soft tissue infections with P. aeruginosa and E. coli have been an issue since both incidence and drug resistance are increasing. In healthy people, P. aeruginosa rarely causes infection; however, it poses a serious health risk in hospitals, where it is responsible for about 10% of in-hospital infections in immunocompromised patients, including those with cancer, diabetes, and hematological disorders, as well as patients undergoing transplant, receiving implants, and being treated with corticosteroids and antibiotics9. In Taiwan, it was reported that E. coli was responsible for almost one-fifth of skin and soft tissue infections10. In Europe, E. coli accounted for 10.8% of infections, and the corresponding rate was 7.2% for North America11. With the observed increase in the rate of bacterial resistance to an extended spectrum of antibiotics, clinical cures and the selection of active antibiotics for empirical treatment may be more difficult to achieve12.
A major component of green tea is a flavonol known as catechin13. (-)-Epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and EGCG are the four main catechins. In particular, EGCG is found only in green tea, comprising 40%~50% of green tea catechins and is thought to be primarily responsible for the antibacterial and bactericidal properties of green tea4,5,6,14,15. Gallocatechin and gallate are necessary moieties for antibacterial activity, with gallate-conjugated (-)-ECG and (-)-EGCG demonstrating more powerful antibacterial activity than non-gallate-conjugated (-)-EGC and (-)-EC14.
It has been reported that the bactericidal effect of EGCG is stronger in Gram-positive bacteria than in Gram-negative bacteria, owing to the different amounts of EGCG absorbed by the bacterial cells6,15,16. While the MIC of EGCG against Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus has been reported to be 50~100 µg/ml, the MIC of EGCG against Klebsiella pneumoniae, Salmonella typhi, and Proteus mirabilis is much higher (800 µg/ml)6. GTE has also shown various degrees of antibacterial activity, and a wide range of susceptibility against different strains of the same species6,17,18. One proposed mechanism for the bactericidal action of catechin is that the negatively charged EGCG combines with the positively-charged bacterial lipid polysaccharide membrane generating hydrogen peroxide (H2O2), which damages the bacterial membrane3,15. Gram-negative bacteria are generally more resistant to catechins than Gram-positive bacteria, due to the presence of strong negative charge of lipopolysaccharides on the exterior outer member of Gram-negative bacteria16. EGCG is known to have unique dual actions, and it protects human keratinocytes and fibroblasts against H2O2 by reversing the H2O2-induced decrease of superoxide dismutase (SOD) and glutathione peroxidase19,20.
The amount of EGCG or catechins in green tea differs depending on the product and extraction method. However, when green tea is infused in hot water for 3 min in a proportion of 1 g of leaves to 100 ml of water, the tea usually contains 250~280 mg of solids, of which 30%~42% are catechins3. When green tea or EGCG capsules are orally administered, only 0.2%~2.0% of the ingested EGCG is intestinally absorbed and appears in the blood17,18. Considering its low plasma concentrations and the reported MIC of EGCG against Gram-negative and Gram-positive bacteria, topical application of EGCG on infected lesions is more desirable than systemic administration, since the concentrations required to treat bacterial infections of the skin cannot be reached through drinking green tea.
Based on the previously reported proportion of catechins in green tea infusions, the estimated concentration of EGCG in the crude infusion of GTE prepared in this study was roughly 400~800 µg/ml21,22. At a GTE dilution level of 1:16, the EGCG concentration was about 25~50 µg/ml. Despite the low concentration of EGCG in the tested GTE, GTE showed antibacterial activity equivalent to 400 µg/ml EGCG. This can be explained through the synergistic antibacterial action of other polyphenols in GTE, such as ECG. Considering that even a 16-fold dilution of crude GTE showed effective antibacterial activity, GTE may be practical and economically feasible for use as an alternative for topical antibiotics or as dressing agents in clinical practices. Furthermore, the clinical application of catechin is plausible, since catechin is very stable under physical manipulations, such as freezing and heating, and can be refrigerated in an aqueous solution for over a month with good stability23,24.
The bacterial strains in this study were isolated from the ulcers and sores of long-stay patients admitted to the ICU. Thus, the incidence of multidrug resistant strains was higher than community acquired strains. However, bacterial strains showing multidrug resistance did not have the same pattern of resistance against EGCG or GTE, and showed susceptibility to EGCG or GTE independent of the antibiotic resistance status. Though the antibacterial effects of EGCG and GTE varied with the individual strains of bacteria, consistent levels of effectiveness were seen regardless of the susceptibility of bacteria to the reference antibiotics. Since EGCG exerts antibacterial effects through diverse mechanisms in vivo, the effective MICs of EGCG against P. aeruginosa and E. coli on skin lesions will be lower than the MICs seen in this study.
Better antimicrobial effects can be expected from GTE than EGCG, since GTE contains various types of catechins with antibacterial activity other than the four major catechins: EGCG, ECG, EGC, and EC. Furthermore, GTE is easily available and would be more cost-effective. Although more studies on their mechanisms of action are needed, EGCG and GTE have great potential for use as topical antimicrobial agents with systemic antibiotics to manage skin infections. Several experiments that tested the ability of EGCG to synergistically inhibit methicillin-resistant S. aureus with concomitant use of oxytetracycline, carbapenem, and ampicillin/sulbactam in vitro demonstrated that EGCG synergistically inhibited bacterial growth25,26,27. An in vivo study of chronic E. coli bacterial prostatitis rat model showed synergistic effects between an oral gavage of 300 mg/kg body weight of catechin concentrate and ciprofloxacin28.
The clinical application of EGCG and GTE is worth considering as a therapeutic in pursuit of overcoming the increasing antibiotic resistance of bacteria and further studies are needed29.
Продвижение полную толщину заживление ран с помощью эпигаллокатехин-3-O-галлат/поли (молочной-со-гликолевой кислоты) мембраны в качестве временной повязки.
Эпигаллокатехин-3-O-галлат (EGCG) является основным полифенольные соединения в зеленом чае. Известно, что EGCG регулирует секрецию цитокинов и активации кожи клеток в процессе заживления ран. В этом исследовании различных концентрациях EGCG были добавлены electrospun мембраны, состоящей из поли (молочной-со-гликолевой кислоты) (на основе), и его целебные эффекты на полную толщину РАН создан в nude мышей были исследованы. В electrospun мембран, содержащие 5 мас.% EGCG (5EGCG/на основе мембраны) выставлены цитотоксичность в человеческих кожных фибробластов (HDFs), как HDF морфологии преобразились на них. В исследовании на животных, клеточная инфильтрация мышей, получавших electrospun мембран, содержащие 1 мас.% EGCG (1EGCG/на основе мембраны) значительно увеличилась после 2-х недель. Иммунореактивность Ki-67 (ре-эпителизации в месте раны) и CD-31 (образование кровеносных сосудов) также увеличилась в мышей, получавших 1EGCG/метода получения мембран в сравнении с мышей, получавших метода получения мембран. Эти результаты позволяют предположить, что 1EGCG/основе может улучшить заживление раны в полной толщины за счет ускорения клеточной инфильтрации, ре-эпителизации, и ангиогенеза.
Artif Organs. 2014 May;38(5):411-7. doi: 10.1111/aor.12190. Epub 2013 Oct 22.