The membrane permeability of Astragali Radix-derived formononetin and calycosin is increased by Angelicae Sinensis Radix in Caco-2 cells: A synergistic action of an ancient herbal decoction Danggui Buxue Tang

Abstract

Danggui Buxue Tang (DBT), a herbal decoction contains Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), has been used as a health food supplement in treating menopausal irregularity in women for more than 800 years in China. Several lines of evidence indicate that the synergistic actions of AR and ASR in this herbal decoction leading to a better pharmacological effect of DBT. Here, the role of different herbs in directing the transport of active ingredients of DBT was determined. A validated RRLC-QQQ-MS/MS method was applied to determinate the permeability of ingredients across the Caco-2 cell monolayer. AR-derived chemicals, including astragaloside IV, calycosin and formononetin, as well as ASR-derived chemicals, including ferulic acid and ligustilide, were determined by RRLC-QQQ-MS/MS. The pharmacokinetic results showed that the membrane permeabilities of calycosin and formononetin, two of the major flavonoids in AR, could be markedly increased in the presence of ASR extract: this induction effect could be mediated by ferulic acid deriving from ASR. In contrast, the extract of AR showed no effect on the chemical permeability. The current results suggested that the ingredients of ASR (such as ferulic acid) could enhance the membrane permeability of AR-derived formononetin and calycosin in cultured Caco-2 cells. The possibility of herb-drug synergy within DBT was proposed here.