Studies On The Chemical Constituents,Antitumor Activities And Related Mechanisms Of Three Medicinal Plants

Medicinal plant resources in our country are abundant,and Traditional Chinese Medicine which has been continuously inherited by several millenniums,play a suggestive role in natural medicine research and development.The study on active components of medicinal plants which have a basis for antitumor activity is the important way to explore natural antineoplastic agents.Potentilla discolor,Ligularia rumicifolia and Croton crassifolius were selected,and their chemical constituents were researched using various separation means.A total of 76compounds were obtained and determined on the basis of classical chemical methods and extensive spectroscopic means.Thirty compounds were identified and classified as terpenoids,steroids,flavonoids,tannins and phenolic acids from Potentilla discolor ethanol extract.Three new C-27-carboxylated-lupane-triterpenoid derivatives?F-1,F-2 and F-3?were established,which were rarely found in nature,and six compounds were firstly isolated from this species.In addition,the essential oil were extracted from Potentilla discolor fresh roots by supercritical CO₂ fluid extraction technology.Twenty-nine compositions were identified by gas chromatography-mass spectrometry?GC-MS?,representing 90.72%of essential oil.Two new monoterpene lactones?Z-1 and Z-2?along with twenty-two known compounds were obtained from the ethanol extract of Ligularia rumicifolia.All compounds were isolated from this species firstly,and they were classified as flavonoids,glycosides,terpenoids,steroids,and phenolic acids.Twenty-two compounds were obtained from Croton crassifolius supercutical CO₂ fluid extract.The type of isolates included terpenoids,steroids and pyrones.J-1 was a new clerodane-type diterpenoids and five compounds were isolated firstly in this species.Six new compounds were evaluated for their in vitro antitumor activities in this study,and compound F-1 exhibited better activity,with the lowest IC₅₀0 value of 17.84?M against HepG-2.The further mechanisms of cellular apoptosis showed that this compound induced HepG-2 cells apoptosis possibly by decreasing the activation of Bcl-2 and stimulating its downstream proteins associated with mitochondria-dependent apoptotic pathway.The antitumor activities of the essential oil was also screened and the lowest IC₅₀0 value was 19.02?g/mL against T-24 cell line.Cell cycle assay confirmed that the cell growth was inhibited and cell cycle was arrested in DNA synthesis phase.Apoptosis analysis indicated that the essential oil induced T-24 cell apoptosis through mitochondrion-mediated intrinsic pathway.In addition,the research progress on biological sources,chemical structures,pharmacological activities and structure-activity relationship of C₁₄-COOH pentacyclic triterpenoids since 1972 were summarized in this thesis.