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柳穿鱼中的抗炎拉蒂烷二萜。

Anti-inflammatory Lathyrane Diterpenoids from Euphorbia lathyris.

机构信息

Wuya College of Innovation , Shenyang Pharmaceutical University , Shenyang 110016 , People's Republic of China.

School of Pharmacy, Tongji Medical College , Huazhong University of Science and Technology , Wuhan 430030 , People's Republic of China.

出版信息

J Nat Prod. 2019 Apr 26;82(4):756-764. doi: 10.1021/acs.jnatprod.8b00600. Epub 2019 Feb 28.

Abstract

Six new lathyrane diterpenoids (1-6) and 10 known analogues (7-16), were separated from the seeds of Euphorbia lathyris. The absolute configuration of 1 was determined by X-ray crystallography, and the C-2' configuration of 5 was elucidated by comparing experimental and calculated ECD data. These compounds were studied for their inhibition against nitric oxide (NO) generation induced by lipopolysaccharide in RAW264.7 macrophage cells. Compounds 1-3, 7, 9, 11, 13, 14, and 16 displayed inhibitory effects on NO production, with IC values of 2.6-26.0 μM. The new compound 1 (IC 3.0 ± 1.1 μM), with no obvious cytotoxicity, was selected for further experiments. The production of cytokines such as IL-6 and IL-1β, as well as the protein expression of iNOS, NF-κB, and phosphorylated IκBα, was reduced by 1 dose-dependently. These results suggested that lathyrane diterpenoids may be used as potential anti-inflammatory agents and are worth being further researched.

摘要

从大飞扬草种子中分离得到了 6 个新的拉蒂烷二萜(1-6)和 10 个已知类似物(7-16)。通过 X 射线晶体学确定了 1 的绝对构型,通过比较实验和计算的 ECD 数据阐明了 5 的 C-2'构型。研究了这些化合物对脂多糖诱导的 RAW264.7 巨噬细胞中一氧化氮(NO)生成的抑制作用。化合物 1-3、7、9、11、13、14 和 16 对 NO 生成具有抑制作用,IC 值为 2.6-26.0 μM。新化合物 1(IC 3.0 ± 1.1 μM),无明显细胞毒性,被选择用于进一步实验。1 剂量依赖性地降低了细胞因子如 IL-6 和 IL-1β的产生以及 iNOS、NF-κB 和磷酸化 IκBα 的蛋白表达。这些结果表明,拉蒂烷二萜可能作为潜在的抗炎剂,值得进一步研究。

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