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首页> 外文期刊>Toxicology: An International Journal Concerned with the Effects of Chemicals on Living Systems >Naturally occurring phenolic acids inhibit 12-O-tetradecanoylphorbol-13-acetate induced NF-kappaB, iNOS and COX-2 activation in mouse epidermis.
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Naturally occurring phenolic acids inhibit 12-O-tetradecanoylphorbol-13-acetate induced NF-kappaB, iNOS and COX-2 activation in mouse epidermis.

机译：天然存在的酚酸可抑制小鼠表皮中的12-O-十四烷酰佛波醇13-乙酸酯诱导的NF-κB，iNOS和COX-2活化。

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摘要

The aim of this study was to investigate the effects of naturally occurring protocatechuic, chlorogenic and tannic acids on the skin tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), induced NF-kappaB in mouse epidermis. The topical application of these phenolics 15min prior to TPA resulted in a significant decrease in the NF-kappaB activation which was measured in terms of p65-DNA binding. Tannic acid was the most potent inhibitor of the TPA-stimulated p65-DNA binding, while chlorogenic acid was the least effective compound. Tannic acid also reduced the most the NF-kappaB p65 subunit translocation from cytosol to the nucleus and enhanced the retention of IkappaBalpha in the cytosol. Although protocatechuic acid decreased p65-DNA binding, it did not affect TPA-stimulated degradation of IkappaBalpha. All the tested compounds inhibited the IkappaBalpha kinase (IKK) activity in mouse epidermis. Tannic acid was the most potent inhibitor and protocatechuic acid the weakest. Tannic and chlorogenic acids reduced the TPA-induced C-L activity of proteasome 20S to a similar extent. The blockade of upstream kinase IKK signaling by tannic acid, but also by protocatechuic acid, inhibited the enzyme level and the activity of COX-2. Protocatechuic acid also diminished the level and activity of TPA-induced iNOS, which might be related to its weak effect on IkappaBalpha degradation. Our earlier studies demonstrated that these compounds, particularly tannic acid, reduced the formation of the polycyclic aromatic hydrocarbon-DNA adducts in vitro and in vivo in mouse epidermis. The results of our present study indicate that the compounds which reduce the formation of electrophilic PAH metabolites may also diminish NF-kappaB activation. Thus, the phenolic acids, particularly tannic acid, by affecting the key events of initiation and promotion stage of carcinogenesis, have become of great interest for the prevention of cancer.
机译：这项研究的目的是调查天然存在的原儿茶酸，绿原酸和鞣酸对皮肤表皮促进剂12-O-十四烷酰佛波醇13-乙酸盐（TPA）诱导的NF-κB的影响。在TPA之前15分钟局部施用这些酚类药物会导致NF-κB活化显着降低，这是通过p65-DNA结合来衡量的。单宁酸是TPA刺激的p65-DNA结合的最有效抑制剂，而绿原酸是效果最差的化合物。单宁酸还减少了大多数NF-κBp65亚基从细胞质到细胞核的转运，并增强了IkappaBalpha在细胞质中的保留。尽管原儿茶酸减少了p65-DNA的结合，但它不影响TPA刺激的IkappaBalpha降解。所有测试的化合物均可抑制小鼠表皮中的IkappaBalpha激酶（IKK）活性。单宁酸是最有效的抑制剂，原儿茶酸是最弱的抑制剂。单宁酸和绿原酸将TPA诱导的蛋白酶体20S的C-L活性降低了相似程度。单宁酸和原儿茶酸对上游激酶IKK信号传导的阻断抑制了酶水平和COX-2的活性。原儿茶酸还降低了TPA诱导的iNOS的水平和活性，这可能与其对IkappaBalpha降解的弱影响有关。我们较早的研究表明，这些化合物（尤其是鞣酸）可在小鼠表皮中体外和体内减少多环芳烃-DNA加合物的形成。我们目前的研究结果表明，减少亲电PAH代谢物形成的化合物也可能减少NF-κB的活化。因此，酚酸，特别是单宁酸，通过影响致癌作用的起始和促进阶段的关键事件，已成为预防癌症的极大兴趣。

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