天津医药(终稿).docVIP

排风藤小分子体外活性研究(付雪娇邹 坤王桂萍张 秀陈剑锋摘要 目的探讨排风藤叔胺生物碱类小分子化合物SCE-1体外IL）-6活性抑制。方法利用细菌脂多糖（LPS）刺激经佛波酯（PMA）诱导的人单核细胞THP-1建立体外炎症模型，四甲基偶氮唑盐微量酶反应比色法MTT）检测的细胞毒性，酶联免疫吸附测定法ELISA）检测药物干预前后上清液中IL-6IL-1β和肿瘤坏死因子TNF）-α的分泌量，综合评价化合物SCE-1对前炎性细胞因子的抑制作用。结果.5~800 mg/L的SCE-1显著抑制了IL-6产生（P0.01），半抑制浓度值为11.82g/L，并且其抑制作用具有时间和剂量依耐性00~800 mg/L的SCE-1对TNF-α的分泌具抑制效应（P＜0.0800 mg/LSCE-1作用2 h(时删掉)抑制率可达53.13%00~800 mg/L的SCE-1促进了IL-1β的分泌（P0.01）。结论该化合物的发现为开发高效低毒特异的小分子IL-6抑制剂提供了一个较好的先导化合物。关键词白细胞介素6白细胞介素1β肿瘤坏死因子αThe inhibitory activity of a novel small molecule IL-6 inhibitor in vitro FU Xuejiao, ZOU Kun,WANG Guiping, ZHANG Xiu, CHEN Jianfeng Hubei Key Laboratory of Natural Products Research and Development, College of Chemistry and Life Sciences, China Three Gorges University, Yichang 443002, China Abstract Objective:To evaluate the inhibition of IL-6 in vitro of a novel tertiary alkaloids small molecule from Solanum cathayanum,named SCE-1.Methods: Inflammation model in vitro was established by lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage;Cytotoxi- city of compound was determined by the mitochondrial-respiration-dependent3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction method and the antagonism activity on proinflammatory cytokine such as interleukin(IL)-6,interleukin 1β(IL-1β),tumor necrosis factor-α(TNF-α) in cell culture medium were determined by enzyme-linked immunosorbent assay(ELISA) methods.Results:Compared with the control group，(1) the SCE-1(12.5~800 mg/L)showed significant dose- and time- dependent inhibitory effect on the production of IL-6 on macrophage-THP-1 cell (P0.01) with an IC50 of 11.82 mg/L; (2) the SCE-1(200~800 mg/L)decreased the production of TNF-α (P0.05 or P0.01),and the inhibition rate was 53.13% at a concentration of 800 mg/L and under 2h treatments; (3) the SCE-1(400~800 mg/L) increased the production of IL-1β (P0.01).Conclusion:In short, the discovery of this compound provided a potential lead compound fo