Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Inflammation. 2015;38(3):941-8. doi: 10.1007/s10753-014-0056-2.
We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-κB (NF-κB) nuclear translocation, inhibitory factor-κB (IκB) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating IκB-α phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-κB and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.
我们从旋覆花中分离出一种新的倍半萜内酯 JEUD-38。JEUD-38 显著抑制脂多糖（LPS）诱导的一氧化氮（NO）产生。与这一发现一致，JEUD-38 以浓度依赖的方式阻断诱导型一氧化氮合酶（iNOS）的蛋白表达。为了阐明机制，我们研究了 JEUD-38 对 LPS 刺激的核因子-κB（NF-κB）核易位、抑制因子-κB（IκB）磷酸化和降解的影响。JEUD-38 通过阻断 IκB-α 的磷酸化和降解来减少 p65 的易位。此外，JEUD-38 抑制 LPS 刺激的丝裂原活化蛋白激酶（MAPKs）包括细胞外信号调节激酶 1/2（ERK1/2）、c-Jun N 端激酶（JNK）和 p38 的磷酸化。由于 iNOS 以及上游 NF-κB 和 MAPKs 被认为与炎症密切相关，这些结果表明 JEUD-38 是预防和治疗炎症性疾病的有前途的候选药物。
