In this research, the isolation and purification of Saussurea lappa root was performed. Three crude extracts, hexane, acetone and methanol, have been prepared, and were subjected to the anti-inflammatory assay by measuring inhibitory activity against nitric oxide (NO) production from LPS-induced macrophage. The hexane extract showed the most potent activity, and was subsequently purified by using chromatographic techniques. Two major compounds, SL-1 and SL-2, were isolated and identified as costunolide and dehydrocostus lactone, respectively. Both compounds are sesquiterpenes and shared the α-methylene-γ-lactone moiety in their structures. It was further found that this functional group is required for the anti-inflammatory activity of SL-1. Further, SL-1 was subjected to ring closure via epoxidation of double bond to yield two eudesmanolide-type sesquiterpenes, cos-2 and cos-3. To extend the compound series, both of them were subjected to acetylation and epoxidation to yield four additional derivatives, cos-4, cos-5, cos-6 and cos-7. All semi-synthetic derivatives were evaluated for their anti-inflammatory. Surprisingly, all displayed potent anti-inflammatory activity with IC₅₀ ranging from 1.81 to 2.17 μM with no toxicity, as well as more potent than costunolide (SL-1). In addition, the cytotoxicity of the compounds against three human cancer cell lines and one non-cancerous cells was assessed. Only costunolide could selectively kill and/or inhibit MCF-7 more than 95% at 20 μM.
