Five New Diarylbutyrolactones and Sesquilignans from Saussurea medusa and Their Inhibitory Effects on LPS-induced NO Production

Abstract

Five new diarylbutyrolactones and sesquilignans (1a/1b – 4), including one pair of enantiomers (1a/1b), together with 10 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.

Key words

Saussurea medusa - Asteraceae - diarylbutyrolactone lignan - sesquilignan - anti-inflammatory activity - molecular docking

Publication History

Received: 04 June 2022

Accepted after revision: 06 October 2022

Accepted Manuscript online:
06 October 2022

Article published online:
10 January 2023

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