Sesquiterpenoid Heterodimers from Artemisia sieversiana with Antihepatic Fibrosis Activity

Abstract

Artesiverins A−I (1−9), nine previously undescribed sesquiterpenoid heterodimers incorporating a guaianolide and a seco-guaianolide, germacranolide, or seco-caryophyllene, were isolated from Artemisia sieversiana Ehrhart ex Willd. (Asteraceae). Their structures were established by spectroscopic analysis, X-ray single-crystal diffraction, and electronic circular dichroism (ECD) data. Compound 1 features a unique carbon framework with a rare tetracyclo[5.2.1.02,6.03,9]dodecane core, formed by head-to-head linkage between a guaianolide and a 1,10-seco-guaianolide. Compound 9 is the first example of a heterodimer comprising guaianolide and seco-caryophyllene monomers. The antihepatic fibrosis assay indicated that compounds 1 and 4 suppressed the expression of fibronectin (FN) and collagen I proteins in TGF-β1-stimulated LX-2 cells in a dose-dependent manner.