Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin
Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin
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DOI：
10.1111/j.1751-1097.1999.tb03267.x
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发表时间：
1999-02-01
影响因子：
3.3
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Katiyar, SK;Matsui, MS;Mukhtar, H
鉴定能够提供对UVB辐射诱导的炎症反应和氧化应激的产生的保护的天然产物可能具有重要的人类健康意义。UVB紫外线照射引起的皮肤损伤和氧化应激与多种皮肤疾病有关，包括光老化、炎症和癌症。茶是世界范围内消费的流行饮料。在几种小鼠技能模型中，局部应用以及口服绿色茶已显示出对化学和UVB诱导的致癌作用和炎症反应提供保护。在本研究中，我们研究了在人体皮肤中，局部应用绿色茶中的主要多酚成分（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是否抑制UVB诱导的白细胞浸润（巨噬细胞/嗜中性粒细胞），产生活性氧（ROS）和产生前列腺素（PG）代谢物的潜在来源，人类受试者在防晒皮肤上进行UVB照射，其最小红斑剂量（MED）为4倍，并在24小时或48小时后获得皮肤活检或角膜切片。我们发现，在UVB（4 MED）暴露于人体皮肤之前，局部应用EGCG（3 mg/2.5 cm（2））可显著阻断UVB诱导的白细胞浸润，并降低髓过氧化物酶活性。这些浸润的白细胞被认为是ROS产生的主要来源。在同一组实验中，我们发现在UVB暴露之前局部应用EGCG减少了UVB诱导的红斑。在另外的实验中，我们发现与单独的UVB暴露相比，来自EGCG预处理的人皮肤并暴露于UVB的微粒体产生显著减少的PG代谢物，特别是PGE，PG代谢产物在多阶段皮肤癌发生中的自由基生成和皮肤肿瘤促进中起关键作用。在更高的放大倍数（x400）下，用苏木精和伊红染色的皮肤切片的仔细显微镜检查也显示，与未预处理的UVB暴露皮肤相比，EGCG预处理和UVB暴露的人皮肤在表皮中含有更少的死细胞。综上所述，我们的数据表明，表没食子儿茶素没食子酸酯有可能阻止UVB诱导的白细胞浸润和随后产生的活性氧在人体皮肤。这可能解释了绿色茶抗炎作用的可能机制。我们认为，表没食子儿茶素没食子酸酯可能是一个有用的局部制剂，对UVB诱导的ROS相关的炎症性皮肤病，光老化和光致癌保护。在这个方向上需要进一步的研究。
Identification of natural products capable of affording protection against UVB radiation-induced inflammatory responses and generation of oxidative stress may have important human health implications. The UVB exposure-induced skin injury and oxidative stress has been associated with a variety of skin disease conditions including photoaging, inflammation and cancer. Tea is a popular beverage consumed worldwide. In several mouse skill models, topical application as well as oral consumption of green tea has been shown to afford protection against chemical and UVB-induced carcinogenesis and inflammatory responses. In the present study, we investigated in human skin, whether topical application of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent in green tea, inhibits UVB-induced infiltration of leukocytes (macrophage/neutrophils), a potential source of generation of reactive oxygen species (ROS), and generation of prostaglandin (PG) metabolites, Human subjects were UVB irradiated on sun-protected skin to four times their minimal erythema dosage (MED) and skin biopsies or keratomes were obtained either 24 h or 48 h later. We found that topical application of EGCG (3 mg/2,5 cm(2)) before UVB (4 MED) exposure to human skin significantly blocked UVB-induced infiltration of leukocytes and reduced myeloperoxidase activity. These infiltrating leukocytes are considered to be the major source of generation of ROS, In the same set of experiments we found that topical application of EGCG before UVB exposure decreased UVB-induced erythema, In additional experiments, we found that microsomes from EGCG pretreated human skin and exposed to UVB, compared to UVB exposure alone, produced significantly reduced PG metabolites, particularly PGE,, The PG metabolites play a critical role in free radical generation and skin tumor promotion in multistage skin carcinogenesis. Careful microscopic examination of skin sections, stained with hematoxylin and eosin, under higher magnification (x400) also revealed that EGCG pretreated and UVB-exposed human skin contained fewer dead cells in the epidermis with comparison to nonpretreated UVB-exposed skin. Taken together, our data demonstrate that EGCG has the potential to block the UVB-induced infiltration of leukocytes and the subsequent generation of ROS in human skin. This may explain the possible mechanism involved in anti-inflammatory effects of green tea. We suggest that EGCG may be useful as a topical agent for protection against UVB-induced ROS-associated inflammatory dermatoses, photoaging and photocarcinogenesis. Further studies are warranted in this direction.