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AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD.
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Aim To establish a LC-MS/MS method for the determination of hydroxysafflor yellow A ( QA ) in human plasma. Methods After being added into 0. 2M ammonium acetate (1∶1,V/V), QA was extrac-ted using solid-phase extraction technique, and the eluent was directly injected into LC-MS/MS systems. Agilent ZORBAX SB C18 (3. 0 × 100 mm, 3. 5 μm) column and isocratic elution system composing of meth-anol and 0. 2 mM ammonium acetate (70 ∶ 30, V/V) provided chromatographic separation of QA and internal standard isorhamnetin-3-O-neohespeidoside ( SLS) fol-lowed by detection with mass spectrometry. The mass transition ion-pair was followed as m/z 611 . 131→490. 900 for QA and m/z 623. 032→298. 800 for SLS. Results The retention time of QA and SLS was 2. 7 min and 3. 9 min respectively, with no interference in human blank plasma. The proposed method showed good linearity over the concentration range of 8. 57 ~4185 μg·L-1 for QA with a correlation coefficient≥ 0 . 9949 . The lower limit of quantitation was 8. 570 μg ·L-1 . The intra-batch and inter-batch precision and accuracy were within 7%. The average matrix effect ranged from 115. 72% to 119. 06% with RSD less than 5%. The average extraction recovery ranged from 77. 75% to 80. 76% with RSD less than 5%. Stability of human samples after 4 h at room temperature, after the three freeze-thaw cycles and after 31 days at -70℃, and post-preparative stability of the processed sam-ples after 24 h was acceptable. Plasma samples with the concentration beyond the upper quantitation limit could be accurately determined after being diluted using 6. 25 times ( V/V ) of human blank plasma. Conclusion Our current LC-MS/MS method is sensitive, accurate and convenient, and is proved to be suitable for the sys-tematic study on clinical pharmacokinetics of QA.
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Aim To investigate the influence of sarpog-relate hydrochloride (SH)on the pharmacokinetic pro-file of dextromethorphan (DM),the typical substrate of CYP2D1 /2,in rats when they were administered co-instantaneously.Methods A total of 1 2 SD rats were randomly divided into two groups:the control group (DM,1 0 mg·kg-1 )and the sarpogrelate group (SH, 1 0 mg·kg-1 ;DM,1 0 mg·kg-1 ),which received in-tragastric administration.Plasma samples were collected immediately before and at different time points after drug administration.A LC-MS /MS method was used to determine the concentrations of DM in rat plasma. Pharmacokinetic parameters were analyzed using Drug and Statistics (DAS 2.0).Results There were signif-icant differences in the pharmacokinetic parameters of DM,including T1 2 (2.49 h ±0.93 h vs 1 .47 h ±0.20 h,P <0.05 ),Cmax (325.7 μg·L -1 ±1 33.2 μg· L -1 vs 1 04.5μg·L -1 ±52.4 μg·L -1 ,P <0.05), AUC0 -t(785.5 μg·L -1 ·h ±451 .9 μg·L -1 ·h vs 244.8 μg·L -1 ·h ±1 68.3μg·L -1 ·h,P <0.05) and AUC0 -∞(804.7 μg·L -1 ·h ±445.6 μg·L -1 ·h vs 251 .4 μg·L -1 ·h ±1 73.4 μg·L -1 ·h,P<0.05 )between the two groups.Conclusion SH could significantly inhibit the elimination of DM,the substrate of CYP2D1 /2 in rats.
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Scientific review, time schedule of ethical review, standards of review, the compensation for injuries of subjects in clinical research and the relation between the ethical review and scientific integrity are common issues in ethical review of clinical research. This paper had an in-depth discussion on issues mentioned above. The interna-tional rules were referred and the personal suggestions were also provided for the reference in further discussion.
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Objective: To explore the operating procedure for designing the randomized scheme of multi-center clinical trial. Methods: SAS randomized program was written in accordance with the randomized parameters and stipulated randomized rules of centers, cases and blocks. The design of the SAS randomized program adopts the same seed in multi-hierarchical factors, and the principles of succession and repeatability of the randomized code. Results: This program can produce randomized numbers and complete the design and permutation of randomized codes in a standard and convenient way.
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0.05).No adverse reactions were found during the clinical trial. Conclusion Yinhua Jiedu Granule is effective and safe in treating wind-heat syndrome of upper respiratory infection and influenza.