The influence of essential oils from Xiang-Fu-Si-Wu Decoction on its non-volatile components and its application for pharmacokinetics in normal rats.

Abstract

Xiang-Fu-Si-Wu Decoction (XFSWD) has been used to treat gynecology diseases in clinical practice for hundreds of years in China, especially for primary dysmenorrheal of QiZhi Type. In previous researches, both essential oils (XEO) and non-volatile components (NXEO) extracted from XFSWD showed significant pharmacological activities, but the influence of XEO on NXEO was unclear. The purpose of this paper was to develop a validated analytical method for simultaneous determination of ten components including Vanillic acid, Ferulic acid, Caffeic acid, Gallic acid, Paeoniflorin, Albiflorin, Tetrahydropalmatine, Protopine, Berberine and Tetrahydrocolumbamine, and to compare the pharmacokinetic parameters of these components to illustrate the influences of XEO on NXEO in normal rats. After being extracted by methanol (1:3, v/v), the plasma samples were analyzed with Clarithromycin (IS1) and Chloramphenicol (IS2) as mixed internal standard (IS). Then the analytes were separated on a ACQUITY UPLC BEH C18 (100×2.1mm, 1.7μm) column with gradient mobile phase (containing 0.1% formic acid aqueous solution and acetonitrile) at a flow rate of 0.4mL/min. All analytes and mixed IS were performed on an electrospray ionization source (ESI) using multiple-reaction monitoring (MRM) with positive and negative ionization mode. The calibration curves of all the analytes showed good linearity (r >0.99), and the lower limits of quantification (LLOQ) were 0.66-46.88ng/mL. The intra- and inter-day precisions ranged 1.24-12.45% and 2.49-13.24% for all the analytes. The mean extraction recoveries of the analytes were in the range of 73.10-93.71% and the average matrix effects were within 82.39-93.18%. The validated method has been fully applied to compare the pharmacokinetic parameters of ten components in rat plasma after oral administration of NXEO, NXEO+β-cyclodextrin (β-CD), NXEO+XEO, and NXEO+β-XEO (the inclusion of XEO by β-CD). It was found that the area under the concentration curves (AUC0-t) of ten constituents in group NXEO+β-CD increased compared with group NXEO especially Paeoniflorin, Tetrahydropalmatine and Tetrahydrocolumbamine (p <0.05). The maximum concentration (Cmax) and AUC0-t of ten compounds in group NXEO+XEO and NXEO+β-XEO had varying degree of increasing in comparison with group NXEO. The growth of group NXEO+β-XEO ran higher than group NXEO+XEO. As can be seen from above-mentioned results, β-CD could remarkably increase the absorption of Paeoniflorin, Tetrahydropalmatine and Tetrahydrocolumbamine. Both of XEO and β-XEO could improve the absorption and bioavailability of all the ten non-volatile compositions. The promotion effect of β-XEO was stronger than XEO due to the double functions of XEO and β-CD.