Semisynthesis, an Anti-Inflammatory Effect of Derivatives of 1?-Hydroxy Alantolactone from Inula britannica.

ABSTRACT: 1?-hydroxy alantolactone, a sesquiterpene lactone mainly isolated from Inula genus plants, exhibits potent anti-inflammatory and anticancer activities. In this work, 1?-hydroxy alantolactone was isolated and five derivatives were prepared through different reactions at the C1-OH and C13-methylene motifs. The structure-activity relationships (SAR) of anti-inflammatory effects against NO production in RAW264.7 cells showed that the ?-methylene-?-butyrolactone motif was essential for NO production suppression and that retaining the C1-OH group can remarkably improve this effect. The NF-?B signaling pathway plays a pivotal role in the regulation of NO expression. Moreover, the levels of p65 and p50 phosphorylation were investigated and active compound 1 inhibited phosphorylation of p65 and p50 in TNF-?-induced NF-?B signaling. Further molecular docking suggested that 1 may target the p65 of NF-?B.

SUBMITTER: Chen L 

PROVIDER: S-EPMC6150205 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature