Pan Li-Long, Xu Peng, Luo Xiao-Ling, Wang Li-Jun, Liu Si-Yu, Zhu Yi-Zhun, Hu Jin-Feng, Liu Xin-Hua
Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Department of Natural Products Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
Biomed Pharmacother. 2017 Apr;88:878-884. doi: 10.1016/j.biopha.2017.01.152. Epub 2017 Feb 6.
The objective of the current study was to evaluate the anti-inflammatory effects of shizukaol B, a lindenane-type dimeric sesquiterpene isolated from the whole plant of Chloranthus henryi, on lipopolysaccharide (LPS)-induced activation of BV2 microglial cells in vitro. Our data showed that shizukaol B concentration-dependently suppressed expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS-stimulated BV2 microglia. Meanwhile, shizukaol B concentration- and time-dependently inhibited LPS-mediated c-Jun N-terminal kinase 1/2 (JNK) activation, but had little effect on extracellular signal-regulated kinase 1/2 or p38 phosphorylation. Furthermore, shizukaol B significantly blocked LPS-induced activator protein-1 (AP-1) activation, evidenced by reduced phosphorylation and nuclear translocation of c-Jun and DNA binding activity of AP-1. Taken together, our findings suggest that shizukaol B exerts anti-inflammatory effects in LPS-activated microglia partly by modulating JNK-AP-1 signaling pathway.
本研究的目的是评估从宽叶金粟兰全草中分离得到的一种单萜类二聚倍半萜——银线草醇B对脂多糖(LPS)诱导的BV2小胶质细胞体外激活的抗炎作用。我们的数据表明,银线草醇B以浓度依赖性方式抑制LPS刺激的BV2小胶质细胞中诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的表达、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的产生。同时,银线草醇B以浓度和时间依赖性方式抑制LPS介导的c-Jun氨基末端激酶1/2(JNK)激活,但对细胞外信号调节激酶1/2或p38磷酸化影响很小。此外,银线草醇B显著阻断LPS诱导的活化蛋白-1(AP-1)激活,这通过c-Jun的磷酸化和核转位减少以及AP-1的DNA结合活性得以证明。综上所述,我们的研究结果表明,银线草醇B在LPS激活的小胶质细胞中发挥抗炎作用部分是通过调节JNK-AP-1信号通路实现的。