Hyperuricemia (HUA) is a metabolic condition caused by excessive production or low excretion of uric acid (UA) in the body. Xanthine oxidase (XOD) is the key enzyme in the process of metabolism purines to generate UA. In this study, the in vitro inhibitory effect of water extract of the flower bud of Sophora japonica (WESJ) on XOD was investigated by ultraviolet spectrophotometry. A mice model of HUA was constructed to explore the effect of WESJ on UA levels and the mechanism of action on renal function. Based on Box–Behnken design, the optimal extraction process of WESJ was determined to extract Sophora japonica twice with 8 times of water, 0.5 h each time. Pharmacological results showed that low, medium, and high doses of WESJ (200, 400, 600 mg/kg) could significantly reduce serum UA level, inhibit the activity of XOD in blood and liver, and have a protective effect on kidney damage caused by high UA. Through UPLC-Q-TOF-MS/MS analysis, 214 compounds were identified in WESJ, including flavonoids, polyphenols, triterpenoids, organic acids, and others. The rat serum of WESJ was analyzed, and 23 prototype components entering the blood were identified, including 15 flavonoids and polyphenols, which may be the main bioactive components. In conclusion, flavonoids and polyphenols in WESJ may reduce the level of UA and alleviate kidney damage by inhibiting the activity of XOD. WESJ is expected to be used as a plant-based food and dietary supplement for the treatment of HUA.
Kaempferol (KPF) is a flavonoid compound, which has a variety of pharmacological activities, and widely exists in daily diet. However, its application is limited due to poor solubility. Citric acid (CA) is a common food additive with high solubility. In this study, solid dispersion (SD) was prepared with CA as the carrier to improve the solubility of KPF. KPF-CA-SD (weight ratio 1:20) was obtained by ultrasonic for 20 min at 40 °C. The in vitro dissolution of KPF in SD was increased from about 50% to more than 80%. The physicochemical characterizations were analyzed by X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscope. In hyperuricemia mice, KPF-SD (equivalent to 100 mg/kg KPF) can effectively reduce serum uric acid and exert nephroprotective effects. In conclusion, the preparation of SD with CA might provide a safe and effective selection to facilitate application of KPF in food and medicine.
Aim: The present study aimed to develop a UHPLC-MS/MS method for determination of vistusertib in biological matrix, and to describe the pharmacokinetic behavior of vistusertib in SD rats. Methodology & results: After protein precipitation with acetone and acetonitrile (1:1), the chromatographic separation was achieved on an Agilent Poroshell 120 EC-C18 column and detected with a SCIEX QTRAP 4500 mass spectrometer under positive ionization mode. The developed UHPLC-MS/MS method showed an excellent linearity within the range of 1.0–3000 ng/ml with good accuracy and precision. Vistusertib showed a rapid absorption and reached the maximum concentration of 3532.2 ± 678.0 ng/ml 20–30 min after oral administration in Sprague-Dawley rats. Conclusion: The established analytical method was fast, sensitive and robust, and successfully applied to describe the pharmacokinetic behavior of vistusertib following an oral administration in rats.
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