Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells.

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 A2/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.

Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components.

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.

Neuroprotective effect of total glycosides from paeonies against neurotoxicity induced by strychnos alkaloids related to recovering the levels of neurotransmitters and neuroendocrine hormones in rat serum and brain.

Semen Strychni, a classical traditional Chinese medicine, has been widely used for its anti-tumor, analgesic and anti-inflammatory angiogenesis effects. However, taking an overdose of Semen Strychni might result in extreme neurotoxicity. Strychnos alkaloids are the main toxic constituents of Semen Strychni. Total glycosides from paeonies are considered to have neuroprotective effects. In this study, twelve potential endogenous biomarkers in rat serum and brain were monitored to investigate the protective effect of total glycosides from the paeony against strychnos alkaloids-induced neurotoxicity. A sensitive liquid chromatography-tandem mass spectrometry method was developed and validated to monitor eight neurotransmitters including glutamate, γ-aminobutyric acid, acetylcholine serotonin, dopamine, norepinephrine, tryptophan and tyrosine. An enzyme-linked immunosorbent assay method was selected for determination of four neuroendocrine hormones including thyrotrophin-releasing hormone, corticotrophin-releasing hormone, antidiuretic hormone and prolactin. Results showed that continuous administration of strychnos alkaloids for 15 days caused significant changed levels of the biomarkers (especially the four neuroendocrine hormones). Meanwhile, total glycosides from paeony pretreated rats (administrated with total glycosides from the paeony for 15 days before exposure to strychnos alkaloids) showed recovered levels of these biomarkers. The results suggested that the neurotransmitters and neuroendocrine hormones in serum and brain might play potential roles as biomarkers. This study provides the possibility of alleviating the Semen Strychni-induced neurotoxicity in clinic by pre-protection with total glycosides from paeonies.

A Chinese character teaching system using structure theory and morphing technology.

This paper proposes a Chinese character teaching system by using the Chinese character structure theory and the 2D contour morphing technology. This system, including the offline phase and the online phase, automatically generates animation for the same Chinese character from different writing stages to intuitively show the evolution of shape and topology in the process of Chinese characters teaching. The offline phase builds the component models database for the same script and the components correspondence database for different scripts. Given two or several different scripts of the same Chinese character, the online phase firstly divides the Chinese characters into components by using the process of Chinese character parsing, and then generates the evolution animation by using the process of Chinese character morphing. Finally, two writing stages of Chinese characters, i.e., seal script and clerical script, are used in experiment to show the ability of the system. The result of the user experience study shows that the system can successfully guide students to improve the learning of Chinese characters. And the users agree that the system is interesting and can motivate them to learn.