Molecular Mechanism of Bailing Capsules in Treatment of Chronic Obstructive Pulmonary Disease Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveThis study aimed to predict the pharmacodynamic material basis and core targets of Bailing capsules in the treatment of chronic obstructive pulmonary disease （COPD） based on network pharmacology and molecular docking， which were further verified by cell experiments to explore the mechanism. MethodThe main active ingredients and related targets of Bailing capsules were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction. The main COPD targets were searched from GeneCards， DrugBank， Online Mendelian Inheritance in Man （OMIM） and Therapeutic Target Database （TTD）. The protein-protein interaction （PPI） network was constructed by STRING and Cytoscape 3.6.1. Gene Ontology （GO） function annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed by the Database for Annotation， Visualization and Integrated Discovery （DAVID）. Molecular docking verification was carried out using AutoDock Vina. The cell viability was detected by 3-（4，5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium （MTS） assay， and the mRNA level of the targets was detected by real-time polymerase chain reaction （Real-time PCR）. ResultA total of 11 active ingredients of Bailing capsules such as cerevisterol， 270 related drug targets， and 1 020 COPD target proteins were obtained， with 74 intersection targets. The visualization analysis of the PPI network showed that the core targets of Bailing capsules in the treatment of COPD were tumor protein P53 （TP53）， catenin beta 1 （CTNNB1）， tumor necrosis factor （TNF）， interleukin-6 （IL-6） and insulin （INS）. Further， 20 signaling pathways were screened by KEGG enrichment analysis as the main pathways for Bailing capsules to treat COPD， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， cyclic adenosine monophosphate （cAMP）， forkhead box O （FoxO）， TNF， and hypoxia inducible factor-1 （HIF-1） signaling pathways. Molecular docking validation demonstrated that four active ingredients had stable binding to IL-6， with the lowest energy. Bailing capsules could reduce the mRNA level of IL-6 in RAW264.7 cells induced by lipopolysaccharide （LPS） （P<0.01） compared with the control group. ConclusionThe pharmacological mechanism of Bailing capsules in the treatment of COPD might be that its main active ingredients improved the inflammatory response by acting on TP53， CTNNB1， TNF， IL-6 and other targets and regulating PI3K/Akt， cAMP and other signaling pathways， thereby ameliorating COPD symptoms. This study provided experimental basis for subsequent in-depth research， and provided a diagnosis and treatment direction for disease-related clinical treatment.

Comparative pharmacokinetic study of the components of Jia-Wei-Kai-Xin-San in normal and vascular dementia rats by ultra-fast liquid chromatography coupled with tandem mass spectrometry.

A fast, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6'-disinapoyl sucrose, α-asarone, ß-asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia-Wei-Kai-Xin-San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04-2.68 ng/mL for all the analytes. Both intra- and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae.

Study on Material Basis and Action Mechanism of Chinese Formula Kai-Xin-San on Anti-depression via Regulation of Neurotrophic Factors / 世界科学技术-中医药现代化

Objective: To observe the material basis and mechanism of action of Kai-Xin-San (KXS) in regulating antidepression of neurotrophic factors. Methods: KXS eluted by ethanol on macroporous resin was prepared. The antidepressive effect of different components was compared by tailing suspension test and forced swimming test of mice. The levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampus were determined by ELISA. The rat astrocyte glioma C6 cell line and the rat adrenal pheochromocytoma PC12 cell line were used to evaluate the effects of different ethanol elution sites on the expression of NGF and BDNF and the differentiation of PC12 cells.Results: All of the ethanol elution components from KXS exerted anti-depressive effects by shorting the immobile time of tailing suspension and forced swimming of mice and 70％ ethanol elution components exerted best efficacy. This site also could increase expressions of NGF and BDNF on C6 glioma cell line. The 10％ ethanol elution site had the strongest ability to promote PC12 cell differentiation. Ginsenosides were the main effectuve ingredients for promoting the expression of neurotrophic factors. Conclusion: Regulation of neurotrophic factors might be the prominent action mechanism of KXS exerting anti-depressive effects.

Mental practice and upper extremity function after stroke / 中华物理医学与康复杂志

Objective To explore the effects of mental practice on upper extremity function after stroke. Methods Thirty sub-acute stroke patients were randomly divided into a treatment group ( n=15 ) and a control group (n=15). The patients in the control group were treated with conventional therapy. The patients in the treat-ment group were treated with motor imagery therapy in addition. All patients were assessed using the Fugl-Meyer mo-tor assessment (FMA) and the motor assessment scale (bIAS) before treatment and after 2, 4 and 8 weeks of treat-ment. Results After 2 weeks of treatment, average MAS scores in the treatment group improved significantly com-pared with before treatment, but there was no significant difference between the two groups. After 4 weeks, FMA and MAS scores in the two groups had improved, and the FMA scores in the treatment group were significantly higher than those of the control group. After 8 weeks, the FMA and MAS scores of both groups had further improved significant-ly, but the average FMA and MAS scores in the treatment group were now significantly higher than those in the control group. Conclusions Mental practice can improve the functional performance of the upper extremities of stroke pa-tients.