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

• Published in: Chinese journal of chemistry Vol. 43; no. 8; pp. 931 - 942
• Main Authors: Weng, Yan‐Mei, Li, Tian‐Ze, Huang, Xiao‐Yan, Li, Qi‐Hao, Chen, Rong‐Kai, Chen, Ji‐Jun
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 15.04.2025; Wiley; Wiley Subscription Services, Inc
• Subjects: Antihepatic fibrosis; Artemisia sieversiana; Artemisieverolides A—G; Chemistry; Chemistry, Multidisciplinary; Circular dichroism; Collagen (type I); Cycloaddition; Dichroism; Fibrosis; Guaianolide trimer; Natural products; Physical Sciences; Science & Technology; Terpenoids; TGF‐β; Trimers; X-ray diffraction; Guaianolide trimer; Antihepatic fibrosis; TGF-beta; Artemisieverolides A-G; NATURAL DISESQUITERPENOIDS; Natural products; Terpenoids; X-ray diffraction; STELLATE CELLS; Artemisia sieversiana; 2 GUAIANOLIDE TRIMERS
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202401216

Comprehensive Summary 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. Artemisieverolides A—G (1—7) were undescribed guaianolide sesquiterpenoid trimers incorporating four types of linkages, especially artemisieverolide A (1) was the first trimer biogenetically through the [2+2] cycloaddition and D‐A reaction. Artemisieverolide C (3) showed inhibitory activity on HSC‐LX‐2 cells with an IC50 value of 52.6 μmol/L. Artemisieverolides B and C (2, 7) suppressed the expression of collagen I in TGF‐β1‐stimulated HSC‐LX‐2.