ABSTRACT
OBJECTIVE To study the immunomodulatory effect of Guipi pills on D-galactose（D-gal）-induced aging mice. METHODS The immune-related targets and related pathways for Guipi pills to exert immune effects were screened by network pharmacology and verified through pharmacodynamic experiments. Totally 105 male ICR mice were randomly divided into blank control （CON） group， model control （MOD） group， positive control （POS） group， Guipi pills low-dose （GD） group and Guipi pills high-dose （GG） group. Except for the CON group， other groups were subcutaneously injected with 400 mg/kg D-gal to induce the aging model； CON group and MOD group were given distilled water， POS group was given 300 mg/kg pidotimod oral solution intragastrically， GD group and GG group were given Guipi pills 300， 600 mg/kg intragastrically， once a day， for 8 weeks. After medication， the serum and spleen were collected， and the contents of interleukin 2 （IL-2）， IL-4， IL-6 and tumor necrosis factor α （TNF-α）， and the contents of immunoglobulin G （IgG）， IgM and IgA were detected. The spleen index was calculated and the histopathological changes in the spleen were observed. The activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH- Px） and malondialdehyde （MDA）， and the content of 8-hydroxy-2 deoxyguanosine （8-OHdG） in spleen were detected； the expression of TNF/phosphoinositide-3-kinase-threonine protein kinase （PI3k-Akt）-related proteins in spleen was detected except for POS group. RESULTS The results of network pharmacology showed that TNF， IL-6 and Akt1 were core targets. The results of pharmacodynamic study showed that compared with MOD group， the contents of IL-2， IL-4， IgG， IgM and IgA were increased significantly in Guipi pills groups， while the contents of TNF-α and IL-6 were decreased significantly； the spleen index was increased significantly （P＜0.05 or P＜0.01）. The phenomenon of diffuse proliferation of lymphocytes was improved， the spleen cells were closely arranged， and the line between the white pulp and red pulp was clear. The activities of SOD and GSH-Px in spleen were increased significantly， while the activity of MDA， the content of 8-OHdG， and the protein expressions of TNF-α， PI3K and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Guipi pills can regulate the immune function of D-gal-induced aging mice， which is related to regulating the TNF/PI3k-Akt pathway， thereby reducing oxidative stress damage in spleen tissue of mice， and regulating protein expressions of TNF-α， PI3K and p-Akt.
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Objective: To explore the mechanism of Leigongteng Pian(Tripterygium wilfordii tablets)for the treatment of rheumatoid arthritis(RA)based on chemomics and network pharmacology. Method: UPLC-Q-TOF/HRMS was used to analyze the chemical constituents of Tripterygium wilfordii tablets under the positive and negative ion modes. Thereafter,the ingredient targets of Tripterygium wilfordii tablets were predicted by Swiss Target Prediction and Pharm- Mapper databases,and the targets of RA diseases were obtained by Traditional Chinese Medicine Systems Pharmacology (TCMSP),Therapeutic Target Database(TTD)and Comparative Toxicogenomics Database(CTD). By taking the inter-section of ingredient targets and disease targets,the direct common targets of Tripterygium wilfordii tablets for the treat- ment of rheumatoid arthritis were obtained. Then the GeneMANIA database was used to obtain indirect targets,and the software of Cytoscape 3.7.1 was used to construct the protein-protein interaction(PPI)networks of potential targets,by which the key targets were screened. Enrichment of gene function and pathways of all potential targets were conducted by Gene Ontology(GO)database and Kyoto Encyclopedia of Genes and Genomes(KEGG)database to explore the mecha- nism of Tripterygium wilfordii tablets for the treatment of rheumatoid arthritis. Results: Thirtyone chemical constituents of Tripterygium wilfordii tablets were screened out and sixtysix potential targets were predicted. Twentyseven active com- ponents in the Tripterygium wilfordii tablets might be important components for the treatment of rheumatoid arthritis as in- dicated by the reverse screening. At the same time,five core targets were screened out,which might be involved in the key pathways that actively participate in the intervention and adjustion of rheumatoid arthritis. Conclusion: In this study,we found that the active components in Tripterygium wilfordii tablets could exert important biological effects via multiple targets and pathways,and these targets and pathways are all involved with the inflammation and immune regula- tion of RA.
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Aim To explore the therapeutic effects of main active compounds of panaxadiol ( PD ) in on Alzheimer’s disease ( AD) via network pharmacologi-cal analysis and Mmolecular docking. Methods A to-tal of 107 prescriptions for AD treatment were screened by using network pharmacology, screening for the high-est frequency of ginseng and its target for AD. Use mo-lecular docking technology was used to find components with the highest score for non-receptor tyrosine kinase ( FYN) docking. Then we successfully estimatedestab-lished AD cell model with overexpressinged APP pro-teins in vitro. Next,the cell viability was detected by MTT assay,the cell damage was detected by LDH as-say,the apoptosis and intracellular Ca2+concentration were detected by flow cytometry, and phosphorylated FYN protein expression was detected by Western blot detection of . phosphorylated FYN protein expression. Results Eighteen active components of Gginseng and 29 AD-related targets were screened by the method of network pharmacology. The results of molecular doc-king showed that PD had strong binding effects with FYN. The results showed that PD could increase the survival rate of cells,reduce the release of LDH,reduce apoptosis,and improve AD cells’ intracellular Ca2+o-verload and reduce the expression of FYN-Y416 pro-tein. Conclusion The experimental results of network pharmacology were are verified and the protective effect of PD on AD may be related to inhibition of FYN signa-ling pathway.
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Aim To explore micro RNAs-integrated pathogenic signaling to control endothelial-mesenchy-mal transition ( EndMT ) in pulmonary hypertension ( PH) by a network bioinformatic approach. Methods Literature-mining method was used to find PH-relat-ed genes and EndMT/EMT-related miRNAs. Bioinfor-matic prediction approach ( DIANA3 , Miranda4 , PicT-ar5 , TargetScan6 , miRDB7 and microT-CDS8 ) was used for miRNA target prediction. Hypergeometric a-nalysis was used to predict miRNAs related to EndMT in PH. The analysis of interactions between PH-rele-vant genes( PH network) was performed with the use of Biological General Repository for Interaction Datasets ( BioGRID ) . These miRNAs were ranked with the highest probability of substantial overlap among their gene targets in the PH-network, the relationship be-tween their targets and the PH functional categories which include hypoxia, inflammation, and transforming growth factor/BMP signaling. Then, the part of results was validated by animal experiment. Lastly the miR-NA-Target network was built using Cytocape 3 . Results List of 230 genes was compiled that were directly im-plicated in the development of PH and 189 miRNAs were related to EndMT in PH. Among 189 miRNAs, only 22 microRNAs(miR-let-7 family, miR-124, miR-130 family, miR-135, miR-144, miR-149, miR-155, miR-16-1, miR-17, miR-181 family, miR-182, miR-200 family, miR-204, miR-205, miR-21, miR-224, miR-27, miR-29 family, miR-301a, miR-31, miR-361 and miR-375) were related to hypoxia, inflamma-tion, and transforming growth factor/BMP signaling. Among these miRNAs, the levels of let-7g, miR-21, miR-124 and miR-130 family were significantly changed in the pulmonary artery in hypoxia-induced PH rats. Conclusions Among numerous miRNAs,22 of which may be involved in hypoxia, inflammation, and transforming growth factor/BMP signaling and re-lated to EndMT in PH by network bioinformatic ap-proach, which provides a theoretical basis for further investigation of EndMT in PH.