A new cytotoxic bufadienolide was isolated from the traditional Chinese medicine-Chansu. The structure of new compound was elucidated on the basis of spectral methods including 2D NMR. And it showed strong in vitro cy...A new cytotoxic bufadienolide was isolated from the traditional Chinese medicine-Chansu. The structure of new compound was elucidated on the basis of spectral methods including 2D NMR. And it showed strong in vitro cytotoxic activity against Hela cells with IC50 of 8.06 × 10^-2μmol/L.展开更多
Chansu has demonstrated adverse reactions in clinical settings,which is associated with its toxicity and limits its clinical applications.But there are methodological limitations for drug safety evaluation.In the curr...Chansu has demonstrated adverse reactions in clinical settings,which is associated with its toxicity and limits its clinical applications.But there are methodological limitations for drug safety evaluation.In the current study,ultra-high performance liquid chromatography,lipidomic profiling,and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets.Compared with the EtOAc extract,Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats,including acute pain(spontaneous raising foot reaction),and inflammation(paw edema).At the molecular level,lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways.However,anti-inflammatory mediators from the CYP 450,ALA,and DHA pathways markedly decreased after exposure to Chansu water fraction.Moreover,four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target,5-HT_(2A)R.These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids,and peripheral 5-HT_(2A)R is a potential target for irritation therapy.The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.展开更多
基金PHR (IHLB) the Beijing Ministry of Education for financial support.
文摘A new cytotoxic bufadienolide was isolated from the traditional Chinese medicine-Chansu. The structure of new compound was elucidated on the basis of spectral methods including 2D NMR. And it showed strong in vitro cytotoxic activity against Hela cells with IC50 of 8.06 × 10^-2μmol/L.
基金This work was supported by the National Natural Science Foundation of China(Nos.82073975,81673563,81102762,and 2018YFC1706200)the Open Project Program of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/Jiangsu Key Laboratory for High Technology Research ofTCM Formulae(Nos.ZDXM-1-14,FJGJS-2015-15)the Fund of Quality Standardization of Liu-Shen-Wan(Nos.BA2016104,ZYBZH-C-JS-30),and Jiangsu Qing Lan Project for Young academic leaders.
文摘Chansu has demonstrated adverse reactions in clinical settings,which is associated with its toxicity and limits its clinical applications.But there are methodological limitations for drug safety evaluation.In the current study,ultra-high performance liquid chromatography,lipidomic profiling,and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets.Compared with the EtOAc extract,Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats,including acute pain(spontaneous raising foot reaction),and inflammation(paw edema).At the molecular level,lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways.However,anti-inflammatory mediators from the CYP 450,ALA,and DHA pathways markedly decreased after exposure to Chansu water fraction.Moreover,four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target,5-HT_(2A)R.These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids,and peripheral 5-HT_(2A)R is a potential target for irritation therapy.The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.
