Active components and potential mechanism of Taohong Siwu Decoction in regulating ischemic stroke based on target cell trapping combined with network pharmacology, molecular docking, and experimental validation / 中国中药杂志

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

Protective effect of medicated serum prepared with taohong siwu tang on hydrogen peroxide-induced human umbilical vein endothelial cells / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effect of medicated serum prepared with Taohong Siwu Tang on hydrogen peroxide-injured human umbilical vein endothelial cells (HUVECs).</p><p><b>METHOD</b>Sprague Dawley rats were orally administered with 10 mL x kg(-1) extracts from Taohong Siwu Tang (1.75 g crude drug), twice a day for three days, in order to prepare medicated serum of Taohong Siwu Tang. The effect of medicated serum pre-treated with Taohong Siwu Tang (with concentrations of 5%, 10%, 15%) on reduction of H2O2-induced cell activity was detected MTT. Cell morphological changes were observed under microscope. The effect of medicated serum prepared with Taohong Siwu Tang on the apoptosis and antioxidant capacity of HUVECs was detected with the content of malondialdehyde (MDA) and dehydrogenase (LDH), the activity of superoxide dismutase (SOD) and AO/EB staining. The expression of Caspase-3 was determined by western blot.</p><p><b>RESULT</b>Compared with the blank serum control group, cell were significantly less active after being damaged by H2O2 (400 micromol x L(-1)). Medicated serum could significantly improve the SOD activity, reduce the levels of LDH and MDA, and inhibite the expression of Caspase-3. AO/EB staining and inverted microscope also showed that medicated serum prepared with Taohong Siwu Tang could reduce cell apoptosis induced by H2O2.</p><p><b>CONCLUSION</b>Medicated serum prepared with Taohong Siwu Tang has significant protective effect on HUVECs injured by H2O2.</p>

Effect of Taohong Siwu decoction on angiogenesis of medicine-induced incomplete-abortion in early pregnancy rats and expressions of Ang-1, Ang-2 and Tie-2 / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of Taohong Siwu decoction (THSWD) on micro-vascular density (MVD) in rat uterus, the content of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in serum, and the expression of tyrosine kinasa receptor (Tie-2) in uterus.</p><p><b>METHOD</b>Early pregnancy rats were intragastrically administrated with misoprostol (100 microg x kg(-1)) and mifepristong (8.3 mg x kg(-1)) to established the incomplete-abortion model. The incomplete-abortion rats were randomly divided into the model group (the same volume of distilled water), the positive control group (at the daily dose of 4.3 g x kg(-1) Motherwort Particles), and THSWD-treated groups (at the daily dose of 18.0, 9.0 and 4.5 g x kg(-1)). Pregnant rats were taken as the control group (the same volume of distilled water). After the successive oral administration for 7 days, blood was collected from aorta abdominalis, and rat uterine tissues were collected. The content of serum Ang-1 and Ang-2 were detected by ELISA; And the levels of Tie-2 and MVD in uterine tissues were detected by SP immunohistochemistry.</p><p><b>RESULT</b>THSWD remarkably increased the levels of MVD in uterus of medicine-induced abortion rats, the content of Ang-1 and Ang-2 in serum, and the expression of Tie-2 in uterine tissues.</p><p><b>CONCLUSION</b>THSWD has the effect in markedly promoting angiogenesis in incomplete-abortion rats. Its mechanism may be related to the regulation of concentrations of Ang-1 and Ang-2 in serum and Tie-2 in uterine tissues.</p>

Effect of sufentanil on calcium-activated potassium currents in rat abdominal aortic smooth muscle cells / 第二军医大学学报

Objective: To investigate the influence of sufentanil on calcium-activated K+ channels (IKCa) in rat abdominal aortic smooth muscle cells, and to investigate its role in dilation of blood vessels. Methods: Rat abdominal aortic smooth muscle cells (AASMCs) were freshly obtained by enzymatic digestion. Whole-cell voltage-clamp technique was used to assess the effect of sufentanil (1 × 10-8, 3 × 10-8, 1 × 10-7 mol/L) on IKCa. Results: Sufentanil significantly increased the amplitude of IKc compared with the control group (P < 0.05 or P < 0.01). The effect of sufentanil was reversible and in a concentration-dependent manner. Conclusion: Sufentanil can promote the activation of KCa channel in rat AASMCs, which might be related to the vasodilatory effect of sufentanil observed in clinical practice.