| Chicoric acid（CA） is a derivative of caffeic acid that occurs naturally in various edible plants and vegetables, especially in Echinacea purpurea and chicory Pharmacological studies have indicated that chicoric acid has many important biological activities, including antioxidant, anti-inflammatory, and anti-HIV activities. Recent studies revealed chicoric acid caninterferemetabolic diseases, such as obesity and diabetes. Considering these useful pharmacological effects, chicoric acid presents excellent potential for development as a functional food factor.However, the absorption and metabolism of chicoric acid in-vivo have not been report yet. The proposed method was used to assess pharmacokinetics, tissue distribution, and plasma protein binding of cichoric acid in rats after gavage administration. The object of this study was to reveal the absorption and metabolism of chicoric acid in experimental animal, to provide guidance for functional food research. The main investigations and results are as follows:（1） Single factor experiments was applied to analyze the influencing factors through the ultrasonic-assisted extraction. The best process parameters of ultrasonic-assisted extraction of chicoric acid were as follows: 60% ethanol, 135 Wof ultrasonic power,40°C, 30 min, solid-liquid ratio 1:40, the optimum yield of chicoric acid was 0.101% under this condition. The purity was 98.4%.（2）A HPLC-MS/MS method was established to determine chicoric acid in rat plasma and various tissues.No endogenous interference was observed at retention times for chicoric acid（3.37 min） or the IS（3.58 min）. The calibration standards were within the concentration range of 0.05-2.0 μg/m L for plasma samples and tissue homogenates. Theregression coefficients（R2） were all higher than 0.996. The lower limits of quantification of chicoric acid in rat plasma and various tissues were between 7.43 and 20.57 ng/m L.The relative standard deviations（RSDs） were measured to be in the range of 2.13-8.06% for intra-day precision and 3.28-10.70% for inter-day precision. The accuracy of intra-day and inter-day should be within 15%. The recoveries ranged from 78.4% to 113.6%.Chicoric acid was stable during the routine analysis.（3）The validated HPLC-MS/MS method was successfully applied to investigate the pharmacokinetics of chicoric acid after gavage administration at a dose of 50.0 mg/kg. Blood samples（0.5 m L） were collected from tail vein and blood was put into heparinized tubes at the designated time points（10, 30, 60, 180, 240, 360, 480, 720 and 1440 min）. The pharmacokinetic parameters were determined and showed a half-life（T1/2） of 738.78 ±152.41 min, an apparent volume of mean residual time（MRT） of 1098.12 ± 181.58 min, and an area under the curve（AUC） of 1558.00 ±392.27 mg min L-1.（4） The validated HPLC-MS/MS method was successfully applied to investigate the tissue distribution and plasma protein binding study of chicoric acid. Various tissues including heart, liver, lung, kidney, spleen, and brain were collected at 1, 3, and 6 h after gavage administration at a dose of 50.0 mg/kg. The tissue distribution of cichoric acid in rats after gavage administration showed a decreasing tendency in different tissues（liver > lung > kidney > spleen > heart > brain）. The PPB rates in rat plasma, human plasma, and bovine serum albumin were 99.0, 97.2, and 96.9%, respectively.In summary, the best process parameters of ultrasonic-assisted extraction of chicoric acid were optimized. With the HPLC-MS/MS method, the pharmacokinetics and tissue distribution investigation of chicoric acid in rats were performed successfully for the first time. The method was demonstrated to be specific, sensitive, and reliable. The results showed that chicoric acid distributed rapidly and widely in various tissues, and was able to cross the blood-brain barrier. Examination of PPB rates showed that chicoric acid has high potential ability to bind with protein. |
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