Theaflavin-3,3′-digallate from black tea blocks the nitric oxide synthase by down-regulating the activation of NF-κB in macrophages

被引:132
作者
Lin, YL
Tsai, SH
Lin-Shiau, SY
Ho, CT
Lin, JK
机构
[1] Natl Taiwan Univ, Coll Med, Inst Biochem, Taipei, Taiwan
[2] Natl Taiwan Univ, Coll Med, Inst Toxicol, Taipei, Taiwan
[3] Rutgers Univ, Dept Food Sci, New Brunswick, NJ USA
关键词
theaflavin-3,3 '-digallate; (-)-epigallocatechin-3-gallate; nitric oxide (NO) synthase; inducible; NF-kappa B (nuclear factor kappa B); I kappa B; macrophage; RAW 264.7 cell line;
D O I
10.1016/S0014-2999(98)00953-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Nitric oxide (NO) plays an important role in inflammation and also in multiple stages of carcinogenesis. We investigated the effects of various tea polyphenols, including theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate, thearubigin, and (-)-epigallocatechin-3-gallate on the induction of NO synthase in lipopolysaccharide-activated murine macrophages, RAW 264.7 cells. Theaflavin-3,3'-digallate was found to be stronger than(-)-epigallocatechin-3-gallate in inhibiting NO generation and inducible NO synthase protein in activated macrophages, while theaflavin, a mixture of theaflavin-3-gallate and theaflavin-3'-gallate and thearubigin were less effective. Inhibition of NO production was observed when cells were cotreated with theaflavin-3,3'-digallate and lipopolysaccharide. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses demonstrated that significantly reduced 130-kDa protein and mRNA levels of inducible NO synthase were expressed in lipopolysacchride-activated macrophages with theaflavin-3,3'-digallate, compared to those without theaflavin-3,3'-digallate. Electrophoretic mobility shift assay (EMSA) indicated that theaflavin-3,3'-digallate blocked the activation of nuclear factor kappa B (NF-kappa B), a transcription factor necessary for inducible NO synthase induction. Theaflavin-3,3'-digallate also blocked phosphorylation of I kappa B from cytosolic fraction and reduced lipopolysacchride-induced nuclear accumulation of transcription factor NF-kappa B p65 and p50 subunits. These results suggest that theaflavin-3,3'-digallate decreases the protein levels of inducible NO synthase by reducing the expression of inducible NO synthase mRNA, and the reduction could be via preventing the activation of NF-kappa B, thereby inhibiting the induction of inducible NO synthase transcription. It was also demonstrated that the gallic acid moiety of theaflavin-3,3'-digallate is essential for their potent anti-inflammation activity. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:379 / 388
页数:10
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