| This thesis is divided into four chapters.The first chapter summarizes the ingenane-type diterpenoids and jatrophane-type diterpenoids and their biological activities of Euphorbia.The second chapter mainly discusses the chemical constituents and biological activities of Euphorbia kansui?kansui?.The third chapter presents the possible mechanism of anti-tumor effect of traditional Chinese medicine kansui by using network pharmacology.The fourth chapter mainly summarizes and forecasts the work of the thesis.In traditional Chinese medicine,the root of kansui has been used as a remedy for ascites,asthma and edema for centuries.Kansui is widely used in clinical practice,such as the treatment of esophageal cancer,acute pancreatitis,cancerous ascites,lung cancer,melanoma,chronic bronchitis,asthma,intestinal obstruction,pertussis.In this article,51 compounds,including sixteen ingenane-type diterpenoids,twenty jatrophane-type diterpenoids,ten triterpenoids and other compounds,were isolated by using sephadex-LH20,silica gel,reversed-phase chromatography?RP-18?and high performance liquid chromatography?HPLC?.Twelve new compounds were identified with 1D and 2D NMR,Optical Rotatory Dispersion?ORD?and high resolution electrospray ionization mass spectroscopy?HR-EI-MS?,which were named as euphorksol A?1?,euphorksol B?2?,euphorksjat A?3?,euphorksjat B?4?,euphorksjat C?5?,euphorksjat D?6?,euphorksjat E?7?,euphorksjat F?8?,euphorksjat G?9?,euphorksjat H?10?,euphorksti A?11?,euphorksti B?12?,respectively.The reversal of multidrug resistance in tumor activity of jatrophane-type diterpenoids were evaluated.The results showed that the compounds have no effect on the proliferation of HepG2/Adr cell.But,when 20?M compounds were combined with different concentrations of doxorubicin?0.5,5,25,50and 100?M?to treat HepG2/Adr cells,the proliferation of HepG2/Adr cell were affected to in varying degrees,compounds 5,6,18 and 19 can increase the sensitivity of HepG2/Adr cells to doxorubicin to a certain extent.Compounds 16,22 exhibited significant activity in reversal of tumor multidrug resistance?RF=143.80,RF=137.77,respectively?,which are significantly better than verapamil?RF=94.24?.Compound16 exhibited significant anti-A/PR/8/34?H1N1?influenza virus?oseltamivir-resistance?activity with IC50=2.31±0.84?M.Compound 19 IC50=1.95±0.50,CC50>30?M),23(IC50=4.85±1.52,CC50>30?M),33(IC50=4.61±0.87,CC50>30?M)and 34(IC50=5.04×10-3±1.59×10-3,CC50=12.30±0.91?M)showed significant activity against HIV-1.The network of chemical constituents of kansui-target,the network of target-signal pathway and the network of target involced in cancer-signal pathway were constructed to explore the mechanism of anti-tumor effect of kansui by the method of network pharmacology.Ingenane-type diterpenoids are considered to be the main components of the anti-tumor effect of kansui,which mainly act on NOS3,RELA,HRAS,NRAS,KRAS,RASGRP1,PEKCA,PRKCB,PRKCE.Furthermore,it has an anti-tumor effect on the RAS-RAF-MEK-MAPK signaling pathway and PLC-PKC signaling pathway in EGFR,VEGF and FGFR signaling systems.However,the specific mechanism still needs further confirmation from biological experiments. |
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