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.

Pharmacokinetic behaviors of four constituents in sugar-free Xinnaosu Granules in rat plasma / 中成药

AIM To investigate the pharmacokinetic behaviors of four constituents in sugar-free Xinnaosu Granules in rat plasma.METHODS Rats intragastrically administered with the 0.5％ CMC-Na suspension of this drug (3 g/kg) had their blood collected for the determination of plasma concentration by UHPLC-MS/MS,after which pharmacokinetic parameters were calculated by DAS2.0 software.RESULTS The plasma concentrationtime curves for tanshinone Ⅱ A,salvianolic acid B,ginsenoside Rg1,notoginsenoside R1 accorded with two compartment model,with the t1/2values of (1.68 ±0.56),(4.13 ±0.87),(3.62 ±0.87),(9.77 ±3.12) h,Tmax values of (0.51 ±0.19),(1 ±0),(6 ±0),(4.00 ±1.09) h,Cmax values of (0.42 ±0.08),(0.17 ±0.02),(0.46±0.11),(0.41 ±0.12) mg/L,respectively.CONCLUSION All the four constituents in sugar-free Xinnaosu Granules demonstrate high bioavailabilities.

Pharmacokinetic Study on Notoginsenoside R1 and Ginsenoside Rg1 in Hushen (Ⅲ) Capsules in Rats / 中国中医药信息杂志

Objective To establish a UHPLC-MS/MS method for the determination of notoginsenoside R1 and ginsenoside Rg1 in rat plasma after oral administration of Hushen (Ⅲ) Capsules; To study its pharmacokinetics. Methods SD rats were given Hushen (Ⅲ) Capsules 2 g/kg and then the blood was collected at time point. Digoxin was used as internal standard. The drug concentrations of notoginsenoside R1 and ginsenoside Rg1 in plasma were determined by UHPLC-MS/MS. And the relative pharmacokinetic parameters were calculated by using DAS2.0 software. Results The linear relationship of notoginsenoside R1 and ginsenoside Rg1 was good (r≥0.997 5). The RSD of intra-day and inter-day precision were less than 13.1%. The results of accuracy, recovery and stability met the requirements for the biology sample analysis. For notoginsenoside R1, the pharmacokinetics parameters T1/2, Tmax, Cmaxin the plasma were (7.86±1.69)h, (4.00±1.04)h, (0.23±0.05)mg/L. For ginsenoside Rg1, the pharmacokinetics parameters T1/2, Tmax, Cmaxin plasma were (4.58±0.95)h, (6.00±0.00)h, (0.32±0.03)mg/L. Conclusion The established UHPLC-MS/MS method is sensitive, accurate and reliable, and is suitable for the pharmacokinetic study of Hushen (Ⅲ) Capsules.

Screen absorption enhancer for intranasal administration preparations of paeoniflorin based on nasal perfusion method in rats / 中国中药杂志

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-β-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

Nasal resorption of prim-O-glucosylcimifugin and 5-O-methylvisammioside in rats / 中国中药杂志

In this experiment, rat nasal mucosa absorption characteristics of prim-O-glucosylcimifugin and 5-O-methylvisammioside were studied to provide a basis for drug delivery of Toutongning nasal spray. The nasal mucosa absorption test in rats was conducted with in situ nasal perfusion method after pH 6 buffer solution was used to prepare high, medium and low concentrations of prim-O-glucosylcimifugin, 5-O-methylvisammioside mixed solution as liquid circulation in nasal cavity. Then the concentrations of the circulating liquid compositions to be measured were determined by HPLC, and the absorption rates of prim-O-glucosylcimifugin and 5-O-methylvisammioside under different pH conditions were also investigated. According to the results, the absorption rate constant was (0.588±0.041)×10⁻³, (0.547±0.023)×10⁻³, (0.592±0.063)×10⁻³ min⁻¹ for prim-O-glucosylcimifugin high, middle and low concentrations, and (0.438±0.041)×10⁻³, (0.407±0.023)×10⁻³, and (0.412±0.063)×10⁻³ min⁻¹ for 5-O-methylvisammioside high, middle and low concentrations. There was no significant difference among high, middle and low concentration groups, and the absorption under pH 6 was better than that under other pH conditions. Therefore, we can get the conclusion that the main active ingredient of Toutongning nasal sprays can be absorbed through the nasal mucosa, and it is feasible to make nasal spray; in addition, pH 6 of nasal spray is scientific and reasonable.