Artemisieverolides A—G, Sesquiterpenoid Trimers from Artemisia sieversiana and Their Antihepatic Fibrosis Activity

Artemisieverolides A—G (1—7), seven unreported sesquiterpenoid trimers, were isolated from Artemisia sieversiana (Asteraceae), and elucidated by comprehensive spectral data and electronic circular dichroism (ECD) calculations. Compounds 1, 2, 4 and 6 were unambiguously determined by the single-crystal X-ray diffraction. Artemisieverolide A (1) was an unprecedented guaianolide sesquiterpenoid trimer featuring a rare 5/7/4/7/5 carbon skeleton biogenetically derived from [2+2] cycloaddition and a 2-methylbicyclo[2.2.1]-2-heptene ring through a Diels-Alder (D-A) reaction. Artemisieverolides B—G (2—7) were guaianolide sesquiterpenoid trimers generated by two D-A reactions. Compounds 3, 4, and 5 exhibited inhibitory activities on the proliferation of HSC-LX-2 with the IC₅₀ values of 52.6, 58.4, and 54.8 μmol/L, and were about 3 folds more active than silybin (IC₅₀ = 149.4 μmol/L). Furthermore, compounds 2 and 7 suppressed the expression of collagen I in TGF-β1-stimulated HSC-LX-2.