| Background. Danshen, the dried root of Salvia miltiorrhiza Bge, is used for treating coronary heart disease. In China, numerous pharmaceutical dosage forms of Danshen are commercially available. Although the pharmacological effects of different components of Danshen are well identified, its absorption as well as pharmacokinetics studies are still insufficient and inconsistent. The current study aims to: (1) screen for the major absorbable active components of Danshen; (2) interpret the absorption mechanism and pharmacokinetics characteristics of the identified components; (3) develop an improved oral drug delivery system for the identified components of Danshen.;Methods. Six major active components in commercially available Danshen products were identified and quantified. In vitro human Caco-2 cell monolayer model, rat in situ intestinal perfusion model as well as rat in vivo pharmacokinetic model were used to investigate the intestinal absorption and pharmacokinetics profiles of the identified Danshen components. Effect of the absorption enhancer on the oral absorption and bioavailabilities of the studied Danshen components was further evaluated.;Results. Danshensu, salvianolic acid B (SAB) and protocatechuic aldehyde (PCA) were identified as the major components in Danshen products. Investigations using in vitro, in situ and in vivo model found that both danshensu and SAB had poor permeabilities and low bioavailabilities (Danshensu: 11.09%; SAB: 3.90%), which may be due to their absorption via the paracellular transport pathways. Studies of PCA suggested that it may have a intestinal first pass metabolism with an oral bioavailability of only 18.02%. It was found that the permeabilities of both danshensu and SAB were significantly increased upon addition of sodium caprate, a paracellular absorption enhancer. The oral bioavailabilities of both danshensu and SAB in pure compound form as well as Danshen extract form were also increased in the presence of sodium caprate in rats.;Conclusion. Both danshensu and SAB have limited intestinal permeability and oral bioavailabilities. Our results demonstrated the usefulness of sodium caprate as a potential absorption enhancer for danshensu and SAB in Danshen product. |
