Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics / 中国中药杂志

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress / 药学学报

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK/PD / 中国中药杂志

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.

Effect of clopidogrel on plasma protein binding rate of ginsenosides: a liquid chromatography-mass spectrometry-based study / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).</p><p><b>METHODS</b>Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.</p><p><b>RESULTS</b>The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.</p><p><b>CONCLUSION</b>Clopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.</p>