Five new diarylbutyrolactones and sesquilignans from Saussurea medusa and their inhibitory effects on LPS-induced NO production

Five new diarylbutyrolactones and sesquilignans (1a/1b−4), including one pair of enantiomers (1a/1b), together with ten known analogues (5−14), were isolated from the whole plants of Saussurea medusa. Compound 1 was found to possess an unusual 7,8'-diarylbutyrolactone lignan structure. Separation by chiral HPLC analysis led to the isolation of one pair of enantiomers, (+)-1a and (−)-1b. The structures of the new compounds were elucidated by extensive spectroscopic data. All compounds, except compounds 5, 7 and 9, were isolated from S. medusa for the first time. Moreover, compounds 1−4, 8 and 10−14 had never been obtained from the genus Saussurea previously. Compounds (+)-1a, 2, 5, 7, and 9−11 were found to inhibit the lipopolysaccharide (LPS)-induced release of NO by RAW264.7 cells with IC₅₀ values ranging from 10.1 ± 1.8 to 41.7 ± 2.1 μM. Molecular docking and iNOS expression experiments were performed to examine the interactions between the active compounds and the iNOS enzyme.