Department of Pharmacology, School of Pharmacy, Fudan university, 826 Zhangheng Road, Pudong New District, Shanghai 201203, China.
Eur J Pharmacol. 2013 May 15;708(1-3):8-13. doi: 10.1016/j.ejphar.2013.01.013. Epub 2013 Jan 23.
A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from Danshensu, exerted cytoprotective effects by anti-oxidative and anti-apoptotic activities in vitro. Herein, we reported the protective effects of DSC on lipopolysaccharide (LPS)-induced inflammatory responses in murine RAW264.7 macrophages and the underlying mechanisms. We showed that DSC concentration-dependently attenuated nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression with less cytotoxicity. Signal transduction studies indicated that DSC significantly inhibited LPS-induced phosphorylation of Akt, but not c-Jun N-terminal kinase 1/2, p38, or extracellular signal-regulated kinase 1/2. Meanwhile, LPS-induced nuclear translocation of nuclear factor-κB (NF-κB) p65 was decreased by DSC. Furthermore, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 significantly suppressed LPS-induced NF-κB p65 nuclear translocation, iNOS expression, and NO production, which was also mimicked by pretreatment with DSC. These results suggested that DSC attenuated LPS-induced inflammatory response in macrophages, at least in part, through suppression of PI3K/Akt signaling and NF-κB activation.
一种新型化合物[4-(2-乙氧基-3-((R)-3-(苄硫基)-1-甲氧基-1-氧代丙-2-基氨基)-3-氧代丙基)-1,2-苯二乙酸酯（DSC）]，来源于丹参素，在体外通过抗氧化和抗凋亡活性发挥细胞保护作用。在此，我们报道了 DSC 对脂多糖（LPS）诱导的小鼠 RAW264.7 巨噬细胞炎症反应的保护作用及其机制。结果表明，DSC 浓度依赖性地减弱了一氧化氮（NO）的产生和诱导型一氧化氮合酶（iNOS）的表达，且细胞毒性较小。信号转导研究表明，DSC 显著抑制 LPS 诱导的 Akt 磷酸化，但不抑制 c-Jun N 末端激酶 1/2、p38 或细胞外信号调节激酶 1/2 的磷酸化。同时，DSC 降低了 LPS 诱导的核因子-κB（NF-κB）p65 的核转位。此外，磷脂酰肌醇 3-激酶（PI3K）抑制剂 LY294002 显著抑制了 LPS 诱导的 NF-κB p65 核转位、iNOS 表达和 NO 产生，而 DSC 的预处理也模拟了这一作用。这些结果表明，DSC 通过抑制 PI3K/Akt 信号通路和 NF-κB 激活，减轻了 LPS 诱导的巨噬细胞炎症反应。
