Studies On Sesquiterpene Lactone Dimers From Vladimiria Souliei And Inula Lineariifolia

Sesquiterpene lactone dimers?SLDs?were small molecule compounds comprised from two homo or hetero sesquiterpene monomers.Most SLDs were derived from two sesquiterpene lactones via Diels-Alder cycloaddition or Michael adduction,which form a novel C30 framework with complex structure.Therefore,these compounds are characterized by various carbon skeletons,multiple connection modes,and diverse three-dimensional configurations.Since the first sesquiterpene lactone dimer,Absinthin,separated from Artemisia absinthium,200 SLDs have been isolated from the natural world.Previously,our group study on three genus from Asteraceae--Inula,Ainsliaea,and Carpesium.79 sesquiterpene lactone dimers with complex structures were isolated,Among them,several SLDs exhibited significant anti-turmor and anti-inflammatory activities.Based on the previous research.In order to find SLDs with new structure and better biological activities,our group focused on Inula lineariifolia and Vladimiria souliei.Our group previously discovered that SLDs show alkaloid false positive reactions of Dragendorff and react with sulfuric acid vanillin chromogenic agent,thus we regard these as instruction of SLDs identification.By combining chromatographic separation technologies,LC-MS track and SLDs identification,we isolated and identified 45 compounds.Among them,9 SLDs with new C₃₂ skeleton type were isolated from the roots of Vladimiria souliei,and 4 new C30 SLDs type were isolated from the Inula lineariifolia.Then,we further evaluated the biological activities of those new SLDs.the following is the summary of these newly discovered SLDs.1.There are 9 SLDs?VS-1⁹?with novel C₃₂ skeleton type from the roots of Vladimiria souliei.There are some common places among them.The common place is that the C₃₂ skeleton comprising two sesquiterpene lactone units linked by a C11-C13? single bond with one acetyl or one ethanol group connected to the C-13 position of one of the two sesquiterpene lactone units.This C₃₂ skeleton type is completely different from the C30 skeleton type.According to the monomers type,SLDs can be divided into guaiane-guaiane type SLDs?VS-1³?,eudesmane-guaiane type SLDs?VS-4⁷?,and germacrane-guaiane type SLDs?VS-8,9?.2.There are 4 SLDs?IL-1⁴?with novel structure separated from Inula lineariifolia.They are derived from two hetero sesquiterpene monoers via Diels-Alder [4+2] cycloaddition,which were linked by two C-C single bonds?1,3-linkage,stereo: exo-/endotypes?,and form the C30 framework.Among them,compound IL-1 was a 4,5-seco-pseudoguaiane-guaiane type SLD with rare exo-configuration,while compounds IL-2⁴ were of xanthane-guaiane type SLDs with endo-configurations.3.We assessed the anti-inflammatory property of newly found SLDs by NO production inhibition assay.Most of them exhibited significant inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages.Among of them,the C₃₂ type SLDs could be more powerful than the positive control?Aminoguanidine?.4.We further assessed the regulation of C₃₂ type SLDs on the NF-?B pathway by Western Blotting and NF-?B luciferase activity.compounds VS-1,2 were found with inhibition towards the NF-?B pathway in the reduction of NF-?B luciferase activity and LPS-induced phosphorylation of the NF-?B p65 subunit.Compounds VS-3,8,9 showed no inhibitory effects on the degradation of I?B?,while possessed inhibitory effects on LPSinduced phosphorylation of the NF-?B p65 subunit.