Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Comparison between Color Doppler Echocardiography and Angiocardiography in Diagnosis of Children's Combined with Congenital Heart Diseases / 实用儿科临床杂志

Objective To evaluate roles of color doppler echocardiography(CDE)and angiocardiography(ANGI)in diagnosis of children's combined with congenital heart diseases(CHD).Methods From Jan.2006 to Jun.2008,31 children with combined with CHD underwent not only CDE but also ANGI.Of those,18 cases were subjected to surgical operation.Main diagnosis and concomitant cardiovascular malformations derived from CDE and ANGI,operative findings as well,were compared.Results In 18 cases undergoing surgery,diagnosis of 15(83.33%)cases from CDE and 17(94.44%)cases from ANGI were in line with the operative findings.Of intracardiac malformations,diffe-rences between CDE and ANGI were:CDE diagnosed 1 case with pulmonary atresia /ventricular septal defect(PA/VSD)as persistent truncus arteriosus(PTA),2 cases with tetralogy of Fallot(TOF)as PA/VSD by mistake,and 1 case with partial anomalous pulmonary venous connection(PAPVC)was suspected by CDE but missed by ANGI,all above mentioned confirmed by sugery;except main diagnosis,CDE missed atrial septal defect(ASD),anomalous origin of right coronary artery and single left coronary for 1 case,respectively.In diagnosing extracardiac abnormal structures:1 case of interrupted aortic arch(IAA)was suspected by CDE but diagnosed and classified by ANGI;for double aortic arch(DAA),pulmonary arteriovenous fistula(PAVF),patent ductus arteriosus(PDA)and absence of right pulmonary artery,1 case of each was missed by CDE;furthermore PDA reported by CDE but not found by ANGI in 4 cases with PA/VSD.Conclusions The diagnostic difference between CDE and ANGI mainly lies in extracardiac malformations including coronary arteries.In diagnosing combined CHD,combination of CDE and ANGI can improve accurate rate.J Appl Clin Pediatr,2009,24(1):44-45