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 IC 50 values of 13.4 ± 1.5 and 15.7 ± 1.1 μM, respectively, which even exceeded the positive control quercetin (IC 50 = 15.9 ± 1.2 μM). Compounds 2 , (+)- 4b , 6 and 9 exhibited moderate inhibitory activities with IC 50 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.