The mechanisms for enhanced oral absorption of hydroxysafflor yellow A by chuanxiong volatile oil.

The aims of this study were to investigate the effect of ligusticum chuanxiong volatile oil (CVO) on the oral absorption of hydroxysafflor yellow A (HSYA). The effects were studied both IN VITRO and IN VIVO. The contents of CVO were measured by GC-MS. The Caco-2 cell model was used to evaluate HSYA permeation with or without the presence of CVO. Transepithelial electrical resistance (TEER) of the Caco-2 cell monolayers was monitored and the alteration in the subcellular localization of claudin-1, the tight junction protein, was observed by immunofluorescence. The irritation of CVO on rat intestine was studied by paraffin slice technology. Our results demonstrated that CVO mainly contained ligustilide (47.82 %). The Papp of HSYA was improved by 5.34-fold and 4.62-fold in the presence of 0.02 mg/mL and 0.01 mg/mL of CVO, respectively. After opening of the tight junctions of the Caco-2 cell monolayer, TEER decreased, the position of claudin-1 changed, and its expression increased. CVO at different concentrations (10, 25, 100 and 200 mg/kg) caused no significant irritation on rat intestine. The bioavailability of HSYA in rats was increased by 6.48-fold and 4.91-fold when 100 and 25 mg/kg of CVO were co-administrated, respectively. CVO was an effective absorption enhancer for oral delivery of BCS III drugs. It can cause redistribution of claudin-1 proteins and open the tight junctions. Georg Thieme Verlag KG Stuttgart New York.