A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.

Chemical Profiling of Nitraria roborowskii Kom. by UPLC-Q-Orbitrap-MS and Their Hypolipidemic Effects in Vivo.

The Nitraria roborowskii Kom. (NRK) berries, as fruits of the genus Nitraria of the Zygophyllceae family, have been widely used as folk medicine. Modern pharmacological research has demonstrated that Nitraria berries had hypolipidemic, hypoglycemic, and immunomodulatory effects. However, more research needs to be reported on the chemical composition and biological activity of NRK. Hence, the phenolic compounds in the NRK berries were comprehensively analyzed and characterized by Ultra Performance Liquid Chromatography-Quadruple-Orbitrap MS system (UPLC-Q-Orbitrap MS) in this study. In total, 52 phenolics were identified, and all were reported for the first time. In addition, the hypolipidemic efficacy of NRK berries extract was studied in the hyperlipidemic mouse model. After treatment, the high dose group of NRK substantially reversed total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels. Through lipidomics technology, 27 potential biomarkers were characterized. And there was a significant callback at 25 of them after NRK treatment by using statistical analysis methods. Pathway analysis results demonstrated that NRK might exert therapeutic effects by regulating glycerophospholipid and glycerolipid metabolism pathways. This study could provide firsthand information on NRK berries for their phenolic compounds and potential application in preventing and treating hyperlipidemia.

Novel albendazole-glucan particles for enhancing intestinal absorption and improving hepatic targeting.

Background: Glucan particles (GPs) are derived from the Saccharomyces cerevisiae cell wall. The hollow particles composed of ß-1,3-D-glucan have been extensively studied in terms of immune regulation and macrophage-targeted drug delivery. Albendazole (ABZ) is a benzimidazole drug with good anti-parasitic activity and is the drug recommended by the World Health Organization for the first-line treatment of hydatid disease. Methods: A dynamic light scatterometer, scanning electron microscope, and transmission electron microscope were used to characterize the ABZ-GPs. High-performance liquid chromatography (HPLC), laser scanning confocal microscope (LSCM) and an in vivo small animal imaging system were used to evaluate theability of ABZ-GPs to be recognized by macrophages, whether ABZ-GPs are more readily absorbed and eliminated in the blood than the original ABZ drug in rats, and the ability of ABZ-GPs to target the mouse liver. Results: The ABZ-GPs were successfully constructed to achieve fluorescence, magnetic resonance imagining, and laser confocal microscopy imaging. The glucan shell effectively protects ABZ from enzymatic degradation and from being pumped out in the gastrointestinal tract. The analysis of ABZ and its major metabolite albendazole sulfoxide in the rat plasma and mouse liver showed that compared to the ABZ suspension group, the degradation of ABZ-GPSs in the blood was low, and the targeting of ABZ-GPSs in the liver was significantly enhanced. Conclusions: In the oral treatment of hepatic hydatid disease, GPs can be used as carriers to achieve the targeted transport of ABZ, which in turn can be used for the targeted therapy of liver echinococcosis. Thus, ABZ-GPs may be a promising form of targeted therapy.