Studies On Sesquiterpene Lactone Dimers From Vladimiria Souliei

Sesquiterpene lactone dimers?SLDs?:Natural small molecular compounds were consisted of two Same type or distinguished type sesquiterpene lactone fragments.At present,most of the dimers found in the world are complex compounds with unparalleled skeleton formed by Diels-Alder cycloaddition reaction or Michale addition reaction.Accordingly,these compounds exhibit many characteristics,such as varied connection modes,various carbon skeletons and diverse three-dimensional configurations.Since the first sesquiterpene lactone dimer absinthin was isolated from Artemisia absinthium,and about more than 200 SLDs have been separated from the natural world.In our previous studies,83 novel SLDs have been found from Ainsliaea,Carpesium and Inula of Asteraceae,and 9 new C₃₂ SLDs have been found from Vladimiria.The results of activity studies also show that several SLDs have significant anti-tumor and anti-inflammatory activities.Based on the previous studies in our group,in order to find more sesquiterpene lactone dimers with novel structure and effective biological activities from Vladimiria,our group focused on Vladimiria souliei.Guided by LC-MS tracing technology and positive reactions of Dragendorff and react with sulfuric acid vanillin chromogenic agent,use various chromatographic separation techniques?MCI column,Sephadex LH-20,RP-C18 and HPLC,etc.?and chromatographic identification techniques?NMR,HR-ESI-MS,X-Ray,IR,UV,CD,OR,etc.?.29compounds were isolated and identified,among them,12 sesquiterpene lactone dimers,including 8 new sesquiterpene lactone dimers and 13sesquiterpene lactone monomers,including 7 guaiacanes,4 gemmalanes,2 eudesmane,1 pentacyclic triterpene and 3 steroids.The sesquiterpene lactone dimers separated are summarized as follows:Structural induction:Eight novel SLDs?Vla-1-8?were isolated from the roots of Vladimiria souliei.They are connected by two homo or hetero sesquiterpene fragments in some way,Among them,Vla-1,is the first member of a new class of SLDs,characterized by a fully hydrogenated pyrrolo[2,1,5-cd]indolizine core scaffold and two sesquiterpene lactone units symmetrically located at each side.Vla-2-6 appear to form from an envisioned rare Diels-Alder[4+2]cycloaddition of two sesquiterpene fragments,and finally forms a C₃₀ skeleton SLDs.Vla-7-8,two C₃₂sesquiterpene lactone dimers comprising of two sesquiterpene lactone units and an acetyl group with the linkage mode of C-C single bonds between C-11/C-13?.Activity Detection:Anti-tumor,anti-inflammatory and neuroprotective activities of the separated dimers were tested.The results showed that these SLDs had no obvious anti-tumor and anti-inflammatory activities,however,Vla-1 and Vla-7 showed better neuroprotective effects,and could protect PC12 cells stimulated by glutamate.At the same time,LDH detection,ROS level detection and Hoechst 33258 staining of Vla-1were carried out.The results also suggested Vla-1 had neuroprotective activities.