Research On The Antitumor Active Constituents From The Roots Of Siraitia Grosvenorii

Siraitia grosvenorii Swingle(Cucurbitaceae)is a perennial plant growing in the southern part of China,Guangxi Zhuang Autonomous Region.It is also one of the first approved Chinese medicinal materials for both food and medicine.Its fruit and leaves are commonly used as medicinal parts,the main effect is to relieve cough and reduce phlegm.In the records of ancient treatises on materia medica,the roots of S.grosvenorii are traditionally used to treat tongue fat,meningitis sequelae,diarrhea and rheumatoid arthritis as a folk medicine in China.However,due to the growing scale of planting,production and processing,a large quantity of S.grosvenorii roots is discarded every year,which results in a great waste of resources.Therefore,it is of great practical significance for environmental protection and the development of the S.grosvenorii industry to extract and separate various natural active ingredients,and explore new drug candidates to turn the roots of S.grosvenorii into a treasure.In the early stage of the experiment,90%ethanol extract was screened for its antitumor activity,and it was found that it showed good anti-proliferation activity on all kinds of tumor cells.Therefore,we conducted a systematic study on its chemical components,hoping to isolate the monomer compounds that can inhibit the proliferation of tumor cells and clarify the basis of its efficacy.The 90%alcohol extracts from the roots of S.grosvenorii were systematically investigated by different chromatographic techniques and 83 compounds were isolated.All the compounds were determined by extensive spectroscopic analysis,including HRESIMS,IR,UV,1H NMR,13C NMR,1H-1H COSY,HSQC,HMBC,NOESY,X-ray and CD.It’s worth noting that DP4+analysis method was applied for the first time to determine the absolute configurations of the trihydroxybutyl moiety in the side chain of compounds SR-1～SR4.Those compounds were identified as 51 triterpenoids(SR-1～SR-51),4 lignans(SR52,SR-74～SR-76),5 sterols(SR-56～SR-58,SR-82,SR-83),5 fatty acids(SR-53～SR55,SR-59,SR-60),7 aromatics(SR-61,SR-66～SR-68,SR-70,SR-73,SR-81),2 diterpenoid lactones(SR-71,SR-72),4 Henn ring compounds(SR-77～SR-80),2 amino acids(SR-63,SR-64),1 furfural compound(SR-65),1 organic acid(SR-69),1 celebroside(SR-62).Among them,23 compounds(SR-1～SR-23)were new,including 4 novel triterpenoid alkaloids(siragrosvenins A-D,SR-1～SR-4)and 4 new cucurbitanetype triterpenoids(siragrosvenins E-F,SR-5～SR-8),and 15 new norcucurbitacin-type triterpenoid glycosides(siraitiaosides A-L,SR-9～SR-23).Siragrosvenins A-D(SR-1～SR-4)possessed a rare cucurbitane-type triterpenoid scaffold,featuring an extra pyrazine unit via strecker reaction in the cucurbitane framework.Siragrosvenin E displays a 6/6/6/5/6/5-fused polycyclic ring system,with uncommon fused furan and pyran rings in the side chain.Siraitiaosides A-L(SR-9～SR23),are fourteen undescribed norcucurbitacin-type triterpenoid glycosides,and this type of triterpenoids is produced in the biosynthetic process of cucurbitacin type triterpenes,which may be generated from cyclizing,rearrangement,or degradation with the loss of one or more carbon atom.Those unique chemical structures have aroused great interest due to the curiosity of its structure-activity relationships,the absolute configurations of some of these compounds are determined by single crystal diffraction.Siragrosvenin D,showing a remarkable cytotoxic activity on MCF-7 cells.As result,it inhibited proliferation of MCF-7 cells and reduced their viability via the induction of G2/M phase arrest,and significantly induced apoptosis in MCF-7 cells,and inhibit the formation of cell colonies.At the same time,this paper reviewed the new cucurbitane-type tetracyclic triterpenoids and their pharmacological activities reported in recent ten years,providing a reference for further interpretation of the structure-activity relationships of cucurbitacins.