Identification of the hydroxylated derivatives of bufalin: phase I metabolites in rats

Abstract

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.

Keywords:

• bufalin
• metabolites
• in vivo
• bile
• hydroxylation

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

^1. These authors (Xiu-Lan Xin and Pei-Pei Dong) contributed equally to this work.

Additional information

Funding

We thank NSFC [grant number 81202589, 81503201], Education Department of Liaoning Province [grant number L2014352], Microbial transformation and metabolism of triterpenoids [grant number YZK 2014020], the Science-Technology Foundation of Beijing Municipal Commission of Education [grant number KM 201510858001], and Beijing Famous Teacher Program [grant number PXM2014-014306-000075] for financial support.