Xin Xiu-Lan, Dong Pei-Pei, Sun Xiao-Hong, Deng Sa, Zhang Ning, Wang Chao, Huo Xiao-Kui, Li Ye, Lan Rong, Chen Liang, Fan Guang-Jun
a College of Bioengineering, Beijing Polytechnic , Beijing 100029 , China.
b College of Pharmacy , Dalian Medical University , Dalian 116044 , China.
J Asian Nat Prod Res. 2016;18(3):239-47. doi: 10.1080/10286020.2015.1071358. Epub 2015 Nov 17.
Bufalin was a typical bioactive bufadienolide, existed in the traditional Chinese medicine Chan Su with the high content of 1-5%. The in vivo metabolites (1-5) of bufalin were prepared by various chromatographic techniques from the bile samples of SD rats, which were administrated with bufalin orally. Their structures were determined on the basis of the widely spectroscopic data, including HRESIMS, 1D-, and 2D NMR. And 1-3, 5 were new compounds. In the in vitro cytotoxicity assay, metabolites (1-5) showed weaker cytotoxic effects than bufalin against human cancer cell lines A549 and H1299, which indicated that the metabolism was a significant pathway for the detoxification of bufalin. Structures analyses indicated that metabolites 1-5 were hydroxylated derivatives of bufalin. This study suggested that Phase I metabolism catalyzed by CYP450 enzymes was one of the metabolic ways of bufalin, which may promote the excretion of bufalin.
蟾毒灵是一种典型的具有生物活性的蟾蜍二烯羟酸内酯，存在于中药蟾酥中，含量高达1 - 5%。通过各种色谱技术从口服蟾毒灵的SD大鼠胆汁样本中制备了蟾毒灵的体内代谢产物（1 - 5）。它们的结构基于广泛的光谱数据确定，包括高分辨电喷雾电离质谱（HRESIMS）、一维和二维核磁共振（NMR）。其中1 - 3、5为新化合物。在体外细胞毒性试验中，代谢产物（1 - 5）对人癌细胞系A549和H1299的细胞毒性作用比蟾毒灵弱，这表明代谢是蟾毒灵解毒的重要途径。结构分析表明，代谢产物1 - 5是蟾毒灵的羟基化衍生物。本研究表明，细胞色素P450酶催化的I相代谢是蟾毒灵的代谢方式之一，这可能促进蟾毒灵的排泄。
