ABSTRACT
Objective:To explore the active components， targets， and signaling pathways responsible for Bushen Zhuyun prescription in treating the recurrent spontaneous abortion （RSA） based on network pharmacology and uncover its potential mechanism by molecular docking and in vitro cell experiments. Method:The active components of Bushen Zhuyun prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） and the published articles， followed by the prediction of drug action targets based on such platforms as DrugBank and SwissTargetPrediction. GeneCards and Online Mendelian Inheritance in Man （OMIM） were searched to obtain the RSA targets， which were then intersected with the targets of Bushen Zhuyun Decoction. Following the plotting of Bushen Zhuyun prescription-compound-target-RSA network by Cytoscape 3.7.1， the protein-protein interaction （PPI） network was then constructed with STRING for screening the core network. The resulting common targets were then subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using R software. Autodock Vina 1.1.2 was used for molecular docking. The activation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/AKT） signaling pathway by Bushen Zhuyun prescription was verified in human umbilical vein endothelial cells （HUVEC） <italic>in vitro</italic>. Result:It was found that 49 potential active components of Bushen Zhuyun prescription might act on 133 RSA targets. GO enrichment analysis yielded 470 biological processes， with angiogenesis， vascular development， cellular proliferation， and oxidative activity mainly involved. KEGG enrichment analysis revealed 103 signaling pathways （<italic>P</italic><0.05）， and the PI3K/AKT signaling pathway， advanced glycation end product （AGE）/receptor for advanced glycation end product （RAGE） signaling pathway， and tumor necrosis factor （TNF） signaling pathway were the main ones. As indicated by molecular docking， the Vina scores of the main active component kaempferol with AKT1 and vascular endothelial growth factor A （VEGFA） were the lowest and similar. It was confirmed <italic>in vitro</italic> cell experiments that Bushen Zhuyun prescription activated the PI3K/AKT signaling pathway and up-regulated the expression of VEGFA and downstream AKT protein to promote angiogenesis. Conclusion:Bushen Zhuyun prescription promotes angiogenesis at the maternal-fetal interface by regulating angiogenesis and cellular proliferation， activating the PI3K/AKT pathway， and up-regulated the VEGFA expression， which is beneficial to the formation of placenta in early pregnancy and the maintenance of early pregnancy. This study has provided ideas for new drug development.
ABSTRACT
This study aims to investigate the protective effect of Dendrobium huoshanense, D.officinale(Huoshan), D.officinale(Yunnan), D.moniliforme and D. henanense on CCl4-induced hepatic damage in mice. C57BL/6 mice were randomly divided into control group, model group, high-dose(7.5 g•kg⁻¹) and low-dose (1.25 g•kg⁻¹) groups of the five Dendrobium. Each group was intragastrically administered with drugs for 2 weeks. The control group was intraperitoneally injected with Olive oil solution, while the other groups were intraperitoneally given 0.5%CCl4combined with Olive oil solution 2 h later after the last administration. Subsequently, ALT and AST activities in serum, SOD activities and MDA contents in liver tissues were determined in all groups 16 h later after administration. The liver index was calculated, and hepatic histopathological examination was performed. The mRNA expressions of IL-1β, IL-6 and TNF-α were analyzed by Real-time PCR. Compared with the CCl4 model group, the activities of ALT and AST in serum decreased significantly in the five different Dendrobium groups. Meanwhile, in liver tissues, the levels of MDA reduced obviously, while the SOD activities markedly increased. Furthermore, liver tissue damage induced by CCl4 was ameliorated according to the histopathological examination. IL-1β, IL-6 and TNF-α mRNA expressions in D.huoshanense-treated liver tissues were significantly decreased. In conclusion, the five different Dendrobium groups showed hepatoprotective effects on CCl4-induced acute liver injury in mice. However, there were differences among Dendrobium of different types and origins. The protect effect of D.huoshanense is the most obvious, and the order of the protective effect of the other Dendrobium from high to low is D.officinale(Yunnan), D. officinale(Huoshan), D.henanense and D.moniliforme. The differences between the different types of Dendrobium might be related to their chemical components.
ABSTRACT
The present study was designed to explore the influence of water extracts of Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of triptolide (TP). A water extract was prepared from A. lancea rhizomes and co-administered with TP in C57BL/6 mice. The toxicity was assayed by determining serum biochemical parameters and visceral indexes and by liver histopathological analysis. The hepatic CYP3A expression levels were detected using Western blotting and RT-PCR methods. The data showed that the water extract of A. lancea rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice using a xylene-induced ear edema test. By comparing ear edema inhibition rates, we found that the water extract could also increase the anti-inflammatory effects of TP. In conclusion, our results suggested that the water extract of A. lancea rhizomes, used in combination with TP, has a potential in reducing TP-induced toxicity and enhancing its anti-inflammatory effects.