Bryonolic Acid Transcriptional Control of Anti-inflammatory and Antioxidant Genes in Macrophages in Vitro and in Vivo
Bryonolic Acid Transcriptional Control of Anti-inflammatory and Antioxidant Genes in Macrophages in Vitro and in Vivo
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DOI：
10.1021/np200823p
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发表时间：
2012-04-01
影响因子：
5.1
通讯作者：
Tochtrop, Gregory P.
中科院分区：
文献类型：
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作者：
Gatbonton-Schwager, Tonibelle N.;Letterio, John J.;Tochtrop, Gregory P.
Bryonolic acid (BA)(1)是一种天然存在的三萜化合物，具有多效性。本研究明确了BA介导抗炎和抗氧化活性的机制，并验证了BA作为探索三萜结构与活性之间关系的工具的实用性。BA通过抑制lps激活的RAW 264.7巨噬细胞中炎症酶诱导型一氧化氮合酶（iNOS）的表达来降低炎症介质NO。此外，BA在体外和体内以nrf2依赖的方式强烈诱导抗氧化蛋白血红素加氧酶-1 （HO-1）。对Nrf2靶基因的进一步分析揭示了BA对巨噬细胞中Nrf2调控抗氧化基因诱导的时间和水平的选择性。此外，相对于齐墩果酸，BA在Nrf2靶基因上的独特表达谱表明，三萜支架在决定这些分子所发挥的多效性作用中的重要性。
Bryonolic acid (BA) (1) is a naturally occurring triterpenoid with pleiotropic properties. This study characterizes the mechanisms mediating the anti-inflammatory and antioxidant activities of BA and validates the utility of BA as a tool to explore the relationships between triterpenoid structure and activity. BA reduces the inflammatory mediator NO by suppressing the expression of the inflammatory enzyme inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 macrophage cells. In addition, BA robustly induces the antioxidant protein heme oxygenase-1 (HO-1) in vitro and in vivo in an Nrf2-dependent manner. Further analyses of Nrf2 target genes reveal selectivity for the timing and level of gene induction by BA in treated macrophages with distinct patterns for Nrf2-regulated antioxidant genes. Additionally, the distinct expression profile of BA on Nrf2 target genes relative to oleanolic acid suggests the importance of the triterpenoid scaffold in dictating the pleiotropic effects exerted by these molecules.