Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

Eight neurotransmitters and four neuroendocrine hormones in rat serum and brain were quantified to investigate the neuroprotective effect of total glycosides from paeony against neurotoxicity induced by strychnos alkaloids.

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study. 2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity. 3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.

Background: Drug stability is essential in the process of drug production, storage, appliance, and so on. Some drugs’ degradation products may even have a toxic side effect, which can result in safety risks and economic losses. Therefore, it is very imperative to develop a suitable stability indicating an analytical method for anastrozole which could be used for stability testing, routine and in-process quality control analysis or other further studies. Methods: A reverse-phase high-performance liquid chromatography method was developed and validated for the degradation kinetics study of anastrozole, a selective non-steroid third-generation aromatase inhibitor, which would provide a basis for further studies on anastrozole. The degradation product was confirmed by ultra-performance liquid chromatography with tandem mass spectrometry. Results: Results showed that the degradation behavior of anastrozole followed first-order kinetics in different temperatures, pH values and oxidation conditions. It was suggested that the degradation behavior of anastrozole was pH-dependent and it’s more stable at lower pH values. Conclusion: A high performance liquid chromatography method was established and used to determine the residual concentration of anastrozole in this study. It was found that the degradation behavior of anastrozole followed first-order kinetics at different temperatures, pH values and oxidation conditions. According to the results, the degradation of anastrozole was found to be pH-dependent and it is more unstable in alkaline conditions. The information of degradation kinetics will be useful for understanding the chemical stability of anastrozole and provide a reference for the further preparation research and clinical therapy of anastrozole.