Study On The Substance Substance Of Xuxiangqing In Reversing The Multidrug Resistance Of Tumor

Chemotherapy is one of the effective methods for the treatment of malignant tumors, and it is widely used in the preoperative, intraoperative and postoperative, but the tumor drug resistance has been seriously affected by chemotherapy for malignant tumor. The research direction of tumor therapy is to find the tumor MDR reversal agent with high efficiency and low toxicity, for the puporse of overcoming the tumor drug MDR and recovering the drug sensitivity of the tumor.To investigate the relationship of C₂₁ steroids with multidrug resistance,Cynanchum paniculatum（Bunge） Kitag.（Asclepiadaceae） which is the authentic ingredients of Shandong Province was choosed as object. The fractionated C₂₁ steroids were evaluated for reversing activities toward human drug-resistance gastric carcinoma cell line SGC-7901/VCR, human drug-resistance colonic carcinoma cell line HCT-8/VCR, and paclitaxel on drug resistance of lung cancer cells A549/T to clininally common used anti-cancer chemotherapeutic drugs doxorubicin（ADM）,cisplatin（DDP）, fluorouracil（5-FU）, and paclitaxel（PAC）. The fractionated C₂₁ steroids exhibited significant effects in sensitization of human drug-resistance gastric carcinoma cell line SGC-7901/VCR to fluorouracil（5-FU） and cisplatin（DDP）, and it also exhibited significant effects in sensitization of human drug-resistance colonic carcinoma cell line HCT-8/VCR to doxorubicin（ADM）, fluorouracil（5-FU） and cisplatin（DDP）, paclitaxel on drug resistance of lung cancer cells A549/T to cisplatin（DDP）.Twenty six compounds were isolated and purified by chromatography on ODS and preparative HPLC. Their structures were elucidated on the basis of chemical and spectroscopic methods, including ESI-MS, 1D and 2D NMR（1H-NMR, 13C-NMR,HSQC, HMBC and NOESY） spectral techniques. Fourteen C₂₁ steroidal aglycones were identified as glaucogenin F（1）, glaucogenin G（2）, neocynapanogenin I（3）,neocynapanogenin J（4）, glaucogenin B（5）, hancogenin B（6）, neocynapanogenin A（7）, neocynapanogenin C（8）, glaucogenin D（9）, neocynapanogenin F（10）,glaucogenin A（11）, 3β,14β-dihydroxy-pregn-5-en-20-one（12）, glaucogenin A（13）,20-hydroxypregna-4,6-dien-3-one（14）; Twelve C₂₁ steroids glycosides were identified as 3β,14β-dihydroxy-17α-pregn-5-en-20-one 3-O-β-D-glucopyranosyl-（1â†'2）-[β-D-glucopyranosyl-（1â†'6）]-β-D-glucopyranoside（15）, 3β,14β-dihydroxy-17α-pregn-5-en-20-one 3-O-β-D-glucopyranosyl-（1â†'2）-β-D-glucopyranoside（16）, 3β,14β-dihydroxy-17β-pregn-5-en-20-one 3-O-β-D-glucopyranosyl-（1â†'2）-[β-D-glucopyranosyl-（1â†'6）]-β-D-glucopyranoside（17）, 3β,14β-dihydroxy-17β-pregn-5-en-20-one 3-O-β-D-glucopyranosyl-（1â†'2）-β-D-glucopyranoside（18）, hancogenin B 3-O-β-D-oleandropyranoside（19）, neocynapanogenin H 3-O-β-D-oleandropyranoside（20）, glaucogenin D 3-O-β-D-oleandropyranoside（21）, neocynapanogenin F 3-O-β-D-oleandropyranoside（22）, glaucogenin C 3-O-β-D-thevetoside（23）, glaucogenin A 3-O-β-D-oleandropyranoside（24）, neocynapanogenin C 3-O-β-D-oleandropyranoside（25）, glaucogenin C 3-O-β-D-oleandropyranoside（26）. Include 10 new compounds, they are 1⁴ and 15²0, 8 were isolated for the first time from natural source, 5⁷ were isolated for the first time from Cynanchum paniculatum.C₂₁ steroids isolated from fractionated extract of Cynanchum paniculatum have potential value as multidrug resistance reversing agents for first time. For the developed with independent intellectual property rights of the high efficiency and low toxicity reversal of tumor multidrug resistance drug innovation lay the basis for drug,which has important academic value and application prospect.