Zhao Jing-Jun, Guo Yan-Qiong, Yang De-Po, Xue Xue, Liu Qin, Zhu Long-Ping, Yin Sheng, Zhao Zhi-Min
School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
J Nat Prod. 2016 Sep 23;79(9):2257-63. doi: 10.1021/acs.jnatprod.6b00355. Epub 2016 Sep 2.
Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.
对日本金粟兰乙醇提取物进行生物活性导向的分离，得到了已知的椴烷型倍半萜类化合物日本金粟兰内酯B（1）。该化合物在脂多糖（LPS）诱导的RAW 264.7巨噬细胞中对一氧化氮（NO）的产生具有显著抑制作用。进一步的抗炎试验表明，化合物1以剂量依赖的方式抑制了一些关键炎症介质如诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平，并减轻了12-O-十四酰佛波醇-13-乙酸酯（TPA）刺激的小鼠的耳厚度和中性粒细胞浸润。机制研究表明，化合物1通过抑制NF-κB信号通路发挥其抗炎作用，该通路抑制了NF-κB依赖性转录活性、IκBα磷酸化和p65核转位。相比之下，发现日本金粟兰内酯B（1）对丝裂原活化蛋白激酶（MAPK）信号通路影响很小。
