Comparative studies on the multi-component pharmacokinetics of Aristolochiae Fructus and honey-fried Aristolochiae Fructus extracts after oral administration in rats

Abstract

Background Aristolochiae Fructus (AF) and honey-fried Aristolochiae Fructus (HAF) have been used in China for a long time as anti-tussive and expectorant drugs. Few clinical cases have been reported to be associated with the toxicity of AF and HAF, although relatively high amounts of aristolochic acids (AAs) have been found in them. Our previous experiments have verified from the chemical changes and from traditional toxicology that honey-processing can significantly reduce the toxicity of AF. To further elucidate the detoxification mechanism of honey-processing, comparative pharmacokinetics of AAs in AF and HAF are performed in this study.MethodsAn HPLC-MS/MS (high-performance liquid chromatography-tandem mass spectrometry) method was developed and validated for the determination of AA I, AA II, AA C, AA D and 7-OH AA I in rat plasma. The multi-component pharmacokinetics of AAs in AF and HAF extracts were investigated after the oral administration of three doses to rats. The relative pharmacokinetic parameters were compared systematically.ResultsThe five AAs shared a similar nonlinear PK (pharmacokinetic) process. They involve rapid absorption and elimination, and they were fit into a two-compartmental open model. Some significant pharmacokinetic differences were observed between the AF and HAF groups: the C max and AUC values of AA I and AA II in the AF groups were much higher than those of the HAF groups.ConclusionsHoney-frying technology can reduce the toxicity of AF by significantly decreasing the absorption of AA I and AA II. The PK parameters obtained in this work could provide valuable references for the toxicity research and clinical use of Aristolochiaceae herbs, including AF and HAF.Graphical abstractProcess diagram of comparative pharmacokinetics study Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1626-2) contains supplementary material, which is available to authorized users.

Multi-Component Comparative Pharmacokinetics in Rats After Oral Administration of Fructus aurantii Extract, Naringin, Neohesperidin, and Naringin-Neohesperidin

“…To evaluate the long-term stability of QC plasma samples, following storage at -20°C for one month. The stability data were acceptable when the bias was within ±15% of the actual value (Yuan et al, 2017).…”

“…The chromatographic separation was achieved on an Agilent C 18 column (2.1x100mm, 1.8mm, Agilent, United States) with temperature at 40°C; The mobile phase was composed of water (containing 0.1% formic acid) (solvent A) and Acetonitrile (solvent B). The gradient elution procedures (0.01-5 min, 30 to 50% B, 5-7min, 50% B, 7-7.5min, 50-30% B, 7.5-10.5min, 30% B); The flow rate was 0.3 ml/min and injection volume was 1.0 ml (Yuan et al, 2017).…”

“…SCXK(Xiang) 2016-0002] weighing 200 ± 20 g were purchased from Hunan Silaike Laboratory Animal Ltd (Changsha, China). The animals were kept in a controlled breeding room with the following conditions: a temperature of 22 ± 2°C, a relative humidity of (65 ± 5)%, and a 12 h light-dark cycle (Yuan et al, 2017). The Experimental Animal Ethic Committee of JXUTCM approved all animal protocols.…”

“…Each calibration curve (y = ax + b) was established by plotting the peak area ratio of analyte to IS (y) against the concentrations (x) of the calibration solution with a least square linear regression. The limit of detection (LOD) and limit of quantification (LOQ) were determined when the peak height was three times and ten times the background noise, respectively (Yuan et al, 2017).…”

“…The intra-and inter-day precisions and accuracies were calculated by an analysis of variance based on the replicate analysis of QC samples, and the work was accompanied by a standard calibration curve on each analytical run (Yuan et al, 2017). Five samples were measured for each concentration level on the optimal conditions five times within the same day for intra-day variance, and the three different days for inter-day variance.…”