Arylnaphthalide lignans from Saussurea medusa and their anti-inflammatory activities

Abstract

Five new arylnaphthalide lignans (1 − 4a/4b), together with five known analogues (5–9), were isolated from whole plants of Saussurea medusa. Compound 4 was characterized as an aryltetralin lignan with an unusual C-7′-C-9 oxygen bridge group, and a chiral HPLC analysis was carried out to afford one pair of enantiomers (4a/4b). Structures of the new compounds were elucidated by extensive spectroscopic and electronic circular dichroism (ECD) calculations. All compounds were firstly isolated from S. medusa, and compounds 1–5, 7 and 8 had never been obtained from the genus Saussurea previously. Furthermore, this is the first report of arylnaphthalide lignans isolated from S. medusa. anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO by LPS-stimulated RAW 264.7 cells. Compounds (−)-4a and 5 exerted the significant inhibition activities with IC50 values of 13.4 ± 1.5 and 15.7 ± 1.1 μM, respectively, which even exceeded the positive control quercetin (IC50 = 15.9 ± 1.2 μM). Compounds 2, (+)-4b, 6 and 9 exhibited moderate inhibitory activities with IC50 values ranging from 19.7 ± 1.9 to 47.4 ± 3.1 μM. Further analysis by molecular docking showed that almost all the active compounds could interact with the amino acid residues of iNOS proteins, which also supported their anti-inflammatory activities.

Keywords

• Saussurea medusa
• Arylnaphthalide lignan
• Anti-inflammatory activity
• ECD calculation
• Molecular docking