Metabolites and the pharmacokinetics of kobophenol A from Caragana sinica in rats
2005
Abstract This research aims to study the metabolism and pharmacokinetics of phytoestrogen kobophenol A ( 1 ), the main active compound of Caragana sinica (Buc’hoz) Rehd. (Fabaceae), in rats. Metabolites of 1 in rats’ feces were isolated and purified by multi-chromatograph techniques; three new metabolites of 1 , named koboquinone A ( M1 ), koboquinone B ( M2 ) and koboquinone C ( M3 ), were isolated, purified from rats’ feces after they being orally administered with 1 . Structure identification of the metabolites was fulfilled by spectroscopic analysis. M1 and M2 are structurally different to those natural occurring stilbene tetramers, which also have para -quinone structure. M1 also showed the activity of stimulating the proliferation of cultured osteoblasts. The pharmacokinetics of 1 in rats could be described by a two-compartmental model ( P 1 was calculated to be 2.0%; rats tissue distribution experiments show that 1 was prominently concentrated in livers. Both of the low oral bioavailability and the rapid reduction of 1 in blood indicated a suitable formulation is needed while it is developed as a new drug.
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