"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Bilateral common carotid artery ligation for creating basilar terminus aneurysm model in rabbits: A preliminary study / 第二军医大学学报

Objective To use bilateral common carotid artery ligation for creating an aneurysm model of the basilar terminus in New Zealand white rabbits. Methods Twenty-sixadult New Zealand white rabbits were subjected to sham operation or bilateral common carotid artery ligation to increase basilar artery flow. Basilar artery flow velocity was monitored by transcranial Doppler before the operation, and 1 d, 1 week, and 4 weeks after surgery. Cerebral angiography was performed 4 weeks after surgery to observe the changes of basilar arteries. The basilar arteries were harvested to observe the morphological changes of the arteries and the histological characteristics of the bifurcation tissues 1 week and 4 weeks after the surgery. Results All animals survived in the sham group, and 80% (16/20) of the animals survived in the experimental group. Thebasilar artery flow velocity increased sharply one day after operation (increased by 226%) in the experimental group, and it kept increasing 1 week after the operation until reaching a stable state 4 weeks after operation. The basal arteries were dilated obviously and displayed tortuous formation after one week in the experimental group, but there was no such change in the sham group. All rabbits in the experimental group presented with thinned media and absent, disrupted or thinned internal elastic lamina near the basilar terminus. Conclusion Blood flow increase at the basilar bifurcation caused by ligation of the bilateral common carotid arteries can lead to aneurysmal change at the basilar terminus of New Zealand white rabbits.