Salvianolic acid A suppress lipopolysaccharide-induced NF-κB signaling pathway by targeting IKKβ
Salvianolic acid A suppress lipopolysaccharide-induced NF-κB signaling pathway by targeting IKKβ
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DOI：
10.1016/j.intimp.2011.07.022
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发表时间：
2011-11-01
影响因子：
5.6
通讯作者：
Lee, Byung Ho
中科院分区：
文献类型：
--
作者：
Oh, Kwang-Seok;Oh, Byung Koo;Lee, Byung Ho
丹酚酸是一种存在于丹参中的活性化合物，是酚类羧酸衍生物((2R)-3-（3,4-二羟基苯基）-2-[（E)-3-[2-RE)-2-（3,4-二羟基苯基）乙烯基]-3,4-二羟基苯基]丙-2-烯基]氧丙酸）。本研究旨在探讨丹酚酸a抗炎作用的潜在机制，特别是通过靶向I κ B激酶β (IKK β)，研究核因子κ B （nf - κ B）信号通路。采用固定化金属磷化亲和（IMAP）时间分辨荧光共振能量转移（TR-FRET）法分析丹酚酸A对IKK β活性的影响。利用脂多糖（LPS）刺激RAW264.7细胞，研究了丹酚酸A的潜在机制。基于IMAP-TR-FRET的IKK β研究表明，丹酚酸A在atp非竞争方式下具有强大的IKK β抑制活性，Ki值为3.63 μ M。丹参酚酸A （10,30 μ M）预处理可降低lps诱导的iNOS和COX-2的表达，从而分别抑制一氧化氮和前列腺素E-2的产生。此外，丹酚酸A （10,30 μ M）也能减弱lps诱导的I κ B α磷酸化和降解，以及nf - κ B易位。这些结果表明，丹酚酸A通过IKK β抑制nf - κ b依赖性炎症通路，这些抗炎作用将有助于理解丹酚酸A的药理学和作用方式。
Salvianolic acid A. an active compound present in Salvia miltiorrhiza, is a phenolic carboxylic acid derivative, ((2R)-3-(3,4-Dihydroxyphenyl)-2-[(E)-3-[2-RE)-2-(3,4-dihydroxyphenyl) ethenyl]-3,4-dihydroxyphenyl] prop-2-enoyl]oxypropanoic acid). The present study was performed to investigate the underlying mechanisms of anti-inflammatory effects with salvianolic acid A. specially focused on nuclear factor kappa B (NF-kappa B) signaling pathway by targeting the I kappa B kinase beta (IKK beta). The effect of salvianolic acid A for IKK beta activity was analyzed using an immobilized metal affinity for phosphochemicals (IMAP)-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay. The underlying mechanisms of salvianolic acid A were examined using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. IKK beta studies based on IMAP-TR-FRET showed that salvianolic acid A possesses a potent IKK beta inhibitory activity with Ki value of 3.63 mu M in an ATP-noncompetitive manner. Pretreatment with salvianolic acid A (10, 30 mu M) decreased LPS-induced expression of iNOS and COX-2, thereby inhibiting production of nitric oxide and prostaglandin E-2, respectively. In addition, salvianolic acid A (10,30 mu M) also attenuated the LPS-induced I kappa B alpha phosphorylation and degradation, and NF-kappa B translocation. These results suggest that salvianolic acid A modulates NF-kappa B-dependent inflammatory pathways through IKK beta inhibition and these anti-inflammatory effects will aid in understanding the pharmacology and mode of action of salvianolic acid A. (C) 2011 Elsevier B.V. All rights reserved.