Эпигаллокатехин egcg лечебные эффекты Кожные болезни Сахарный диабет Ожирение Научные исследования Укрепления здоровья эффекты зеленого чая




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Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage.


Syed F1, Bagabir RA, Paus R, Bayat A.

Author information


  • 1Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology (MIB), University of Manchester, Manchester, UK.

Abstract


Keloid disease (KD) is a common fibroproliferative disorder of unknown etiopathogenesis. Its unique occurrence in human skin and lack of animal models pose challenges for KD research. The lack of a suitable model in KD and over-reliance on cell culture has hampered the progress in developing new treatments. Therefore, we evaluated the effect of two promising candidate antifibrotic therapies: (-)-epigallocatechin-3-gallate (EGCG) and plasminogen activator inhibitor-1 (PAI-1) silencing in a long-term human keloid organ culture (OC). Four millimeters of air-liquid interface (ALI) keloid explants on collagen gel matrix in serum-free medium (n=8 cases) were treated with different modalities (EGCG treatment; PAI-1 knockdown by short interfering RNA (siRNA) and application of dexamethasone (DEX) as control). Normal skin (n=6) was used as control (only for D0 keloid-untreated comparison). Besides routine histology and quantitative (immuno-) histomorphometry, the key phenotypic and growth parameters of KD were assessed. Results demonstrated that EGCG reduced keloid volume significantly (40% by week 4), increased apoptosis (≥40% from weeks 1 to 4), and decreased proliferation (≤17% in week 2). EGCG induced epidermal shrinkage, reduced collagen-I and -III at mRNA and protein levels, depleted 98% of keloid-associated mast cells, and reduced the percentage of both cellularity and blood vessel count by week 4. Knockdown of PAI-1 significantly reduced keloid volume by 28% in week 4, respectively, and reduced collagen-I and -III at both mRNA and protein levels. As expected, DEX increased keloid apoptosis, decreased keloid proliferation, and collagen synthesis, but induced connective tissue growth factor overexpression. In conclusion, using keloid OC model, we provide the first functional evidence for testing candidate antifibrotic compounds in KD. We show that EGCG and PAI-1 silencing effectively inhibits growth and induces shrinkage of human keloid tissue in situ. Therefore, the application of EGCG, PAI-1 silencing, and other emerging compounds tested using this model may provide effective treatment and potentially aid in the prevention of recurrence of KD following surgery.

Эффект и механизм эпигаллокатехин-3-галлат (EGCG). против перекись водорода-индуцированного окислительного повреждения в человеческих дермальных фибробластов.

Было проведено исследование с целью изучения защитного действия эпигаллокатехин-3-галлат (EGCG), перекись водорода (Н2О2)-индуцированного окислительного стресса, травмы в человеческих дермальных фибробластов. 3-(4,5-Dimethylthiazol-2-ил)-2,5-diphenyltetrazolium бромид (МТТ) колориметрический анализ и использование окрашивание Hoechst и terminal deoxynucleotidyl transferase dUTP nick end labeling для обнаружения апоптоза указал, что администрация H2O2 человеческих дермальных фибробластов причиной повреждения клеток и апоптоз. Инкубационный человеческих дермальных фибробластов с EGCG значительно ингибировал человеческих дермальных фибробластов травмы, индуцированной Н2О2. Анализа для 2,2-дифенил-1-picrylhydrazyl антирадикальное деятельности показали, что EGCG был прямой, зависящей от концентрации антиоксидантной активностью. Лечение человеческих дермальных фибробластов с EGCG значительно отменил H2O2-индуцированное снижение супероксиддисмутазы (СОД) и глутатионпероксидазы (GSH-px), и ингибирование малонового диальдегида (мда) уровнях. Эти результаты показали, что EGCG обладали антиоксидантной активностью и был эффективен в отношении Н2О2-индуцированной человеческих дермальных фибробластов травмы при повышении активности СОД и GSH-px, а также за счет снижения уровня мда. Наши результаты позволяют предположить, что EGCG должен иметь потенциальную возможность быть в дальнейшем использован в косметике, так и в профилактике старения, связанных с кожа травм.



J Cosmet Sci. 2013 Jan-Feb;64(1):35-44.

Effect and mechanism of epigallocatechin-3-gallate (EGCG). against the hydrogen peroxide-induced oxidative damage in human dermal fibroblasts.


Feng B1, Fang Y, Wei SM.

Author information


  • 1School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.

Abstract


This study was conducted to investigate the protective effects of epigallocatechin-3-gallate (EGCG) on hydrogen peroxide (H2O2)-induced oxidative stress injury in human dermal fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and the use of Hoechst staining and terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptosis detection indicated that the administration of H2O2 to human dermal fibroblasts caused cell damage and apoptosis. The incubation of human dermal fibroblasts with EGCG markedly inhibited the human dermal fibroblast injury induced by H2O2. The assay for 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity indicated that EGCG had a direct, concentration-dependent antioxidant activity. Treatment of human dermal fibroblasts with EGCG significantly reversed the H2O2-induced decrease of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), and the inhibition of malondialdehyde (MDA) levels. These results showed that EGCG possessed antioxidant activity and was effective against H2O2-induced human dermal fibroblast injury by enhancing the activity of SOD and GSH-px, and by decreasing the MDA level. Our results suggested that EGCG should have the potential to be used further in cosmetics and in the prevention of aging-related skin injuries.


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