Studies On Chemical Constituents From Ganoderma Lucidum And Their MDR Reversal Activity

OBJECTIVE:To explore the reversal activity on MDR of triterpenoids from Ganoderma lucidum.METHODS: Soxhlet extraction and ultrasonic method was employed for the extraction of the total triterpenoids from Ganoderma lucidum.Silica gel column chromatography,thin-layer chromatography,semi-preparative HPLC and other means were used to carry out the extraction and purification of total triterpenoids.MTT assay was used to detect anti-tumor and reversal activity on MDR.Structures were identified by spectral analysis and other means.RESULTS: 2 new compounds named ethyl7?,15?-dihydroxy-3,11,23-trioxo-5?-lanost-8-en-26-oate(B11-1-9)and ethyl7?,15?-dihydroxy-3,11,23-trioxo-5?-lanost-8-en-26-oate(B11-1-11)were obtained from Ganoderma lucidum,and they are enantiomers particularly.And 1 known compounds named lucidone B(B11-3-4),were obtained and there was one compound named B11-3-10 under structural identification.B11-3-4 and B11-1-9 have the weak inhibition on different tumor cells,their IC50 were all greater than 100 ?g/ml.Compound B11-1-11 can significantly inhibit the proliferation of K562 cells and HL-60 cells,the I C50 were 15.60 ?g/ml,16.70 ?g/ml respectively.Anticancer activity of B11-1-4 is weak on all tumor cells.In certain concentration,the compounds were tested with ADR in cell line KBv200 for 48 h,the reversal times of compounds B11-1-9,B11-1-11 in 10?g/ml concentrations were 6.44 and 15.91 times;B11-3-4 in10?g/ml concentrations didn't reverse MDR.In the 10?g/ml concentration,the reversal times of B11-3-10 was 55.76 times.B11-3-10 can increase the accumulation of ADR in KBv200 cells and increase the cytotoxicity of ADR to KBv200 cells in a concentration dependent manner.CONCLUSION:2 new structures of active components(B11-1-9,B11-1-11),1 known compound(B11-3-4)and 1 compound under identification(B11-3-10)were obtained from Ganoderma triterpenoid.Compared with GA-A,B11-1-9 and B11-1-11 can reverse the tumor MDR on KBv200,and ethyoxyl may be related to the effect.Compared with B11-1-9,the structure of B11-1-11 is different only in 7 site,But the reversal effect were a little different.The configuration of hydroxyl group in 7 site may has an effect on the reversal effect of MDR.Compound B11-3-10 can increase the accumulation level of ADR on KBv200 and increase the cytotoxicity of ADR in a concentration dependent manner.The reversal effect may be related to the inhibition of P-gp,which increased the levels of ADR in the cell.