Katiyar S K, Matsui M S, Elmets C A, Mukhtar H
Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106, USA.
Photochem Photobiol. 1999 Feb;69(2):148-53.
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 skin 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 cm2) 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 PGE2. 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.
鉴定能够预防紫外线B辐射诱导的炎症反应和氧化应激产生的天然产物可能对人类健康具有重要意义。紫外线B暴露诱导的皮肤损伤和氧化应激与多种皮肤疾病状况有关,包括光老化、炎症和癌症。茶是一种在全球广泛消费的流行饮品。在多个小鼠皮肤模型中,局部应用以及口服绿茶已被证明能够预防化学物质和紫外线B诱导的致癌作用及炎症反应。在本研究中,我们在人体皮肤中研究了局部应用绿茶中的主要多酚成分(-)-表没食子儿茶素-3-没食子酸酯(EGCG)是否能抑制紫外线B诱导的白细胞(巨噬细胞/中性粒细胞)浸润,白细胞是活性氧(ROS)产生的潜在来源,以及前列腺素(PG)代谢产物的产生。对人体受试者受阳光保护的皮肤进行紫外线B照射,剂量为其最小红斑剂量(MED)的四倍,在24小时或48小时后获取皮肤活检样本或角质层切片。我们发现,在紫外线B(4 MED)照射人体皮肤之前局部应用EGCG(3毫克/2.5平方厘米)可显著阻断紫外线B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,我们发现紫外线B照射前局部应用EGCG可减轻紫外线B诱导的红斑。在额外的实验中,我们发现与仅接受紫外线B照射相比,来自EGCG预处理的人体皮肤并暴露于紫外线B的微粒体产生的PG代谢产物显著减少,尤其是前列腺素E2。PG代谢产物在多阶段皮肤致癌过程中的自由基产生和皮肤肿瘤促进中起关键作用。用苏木精和伊红染色的皮肤切片在高倍镜(×400)下仔细显微镜检查还显示,与未预处理的紫外线B照射皮肤相比,EGCG预处理并紫外线B照射的人体皮肤表皮中的死细胞较少。综上所述,我们的数据表明EGCG有潜力阻断紫外线B诱导的人体皮肤白细胞浸润以及随后的ROS产生。这可能解释了绿茶抗炎作用的潜在机制。我们认为EGCG可能作为一种局部用药,用于预防紫外线B诱导的与ROS相关的炎症性皮肤病、光老化和光致癌作用。有必要在这个方向上进行进一步研究。