目的:利用已发表的半夏生物总碱(pinellia total alkaloid,PTA)与钩藤生物总碱(uncaria total alkaloid,UTA)联合抗惊厥和毒性作用数据,全面定量评价其相互作用和组方合理性。方法:采用等效图法(isobologram)和计算机模拟技术,定量评价...目的:利用已发表的半夏生物总碱(pinellia total alkaloid,PTA)与钩藤生物总碱(uncaria total alkaloid,UTA)联合抗惊厥和毒性作用数据,全面定量评价其相互作用和组方合理性。方法:采用等效图法(isobologram)和计算机模拟技术,定量评价不同强度(0%～99%)有效剂量(ED)和致死剂量(LD)的相互作用,并综合计算其获益指数(BI)和治疗指数(TI)。结果:3个配比(PTA∶UTA=1∶4,1∶1,4∶1)有协同作用趋势。由于最高剂量的有效率均低于70%,给参数计算和研究结论带来不确定性。PTA和UTA按4∶1联用的毒性呈现拮抗作用,其它2个配比毒性拮抗作用不明确。基于ED和LD参数的综合分析,3个配比的BI均大于1,其中4∶1配比的减毒增效作用明确,TI增大。结论:PTA和UTA按4∶1给药后安全性和有效性提高,呈现配伍优势。从方法学角度,本研究可对同类实验的设计和分析提供参考。展开更多
Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT1...Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.展开更多
文摘目的:利用已发表的半夏生物总碱(pinellia total alkaloid,PTA)与钩藤生物总碱(uncaria total alkaloid,UTA)联合抗惊厥和毒性作用数据,全面定量评价其相互作用和组方合理性。方法:采用等效图法(isobologram)和计算机模拟技术,定量评价不同强度(0%～99%)有效剂量(ED)和致死剂量(LD)的相互作用,并综合计算其获益指数(BI)和治疗指数(TI)。结果:3个配比(PTA∶UTA=1∶4,1∶1,4∶1)有协同作用趋势。由于最高剂量的有效率均低于70%,给参数计算和研究结论带来不确定性。PTA和UTA按4∶1联用的毒性呈现拮抗作用,其它2个配比毒性拮抗作用不明确。基于ED和LD参数的综合分析,3个配比的BI均大于1,其中4∶1配比的减毒增效作用明确,TI增大。结论:PTA和UTA按4∶1给药后安全性和有效性提高,呈现配伍优势。从方法学角度,本研究可对同类实验的设计和分析提供参考。
基金supported by the Ministry of Higher Education,Malaysia(No.UKM-JJ-03-FRGS0044-2010)Universiti Kebangsaan Malaysia(No.UKM-DPP-2014-131)
文摘Objective： The combination effect of Piperbetle （PB） and 5-fluorouracil （5-FU） in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated. Methods： HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography （HPLC） was performed to exclude any possible chemical interaction between the compounds. Results： In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose （IC^0 12.5 pmol/L） and a shorter time （24 h） in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively. Conclusions： In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
