BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

OBJECTIVE To explore the medication rule and potential mechanism of anti-aging traditional Chinese medicine health care prescription by using data mining,network pharmacology and molecular docking technology.METHODS By searching the special food information query platform of the State Administration for Market Regulation and Yaozhi.com,the health care prescrip-tions with traditional Chinese medicine as the main component and anti-aging effect were searched.The data mining technology was used to analyze the prescription rules,and the core anti-aging traditional Chinese medicine was selected according to the analysis re-sults.The chemical constituents and corresponding targets of core anti-aging traditional Chinese medicines were obtained by searching TCMSP and other databases;potential targets related to aging from GeneCards and OMIM databases were screened;the intersection tar-gets of core Chinese medicine and aging were obtained.Subsequently,protein-protein interaction(PPI)network analysis,gene ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using STRING database and Cytoscape 3.7.2 software.Finally,the affinity of core targets and key components was verified by molecular docking technology.RESULTS A total of 244 kinds of anti-aging traditional Chinese medicine health care prescriptions were screened and included.The prescription drugs were mainly tonic drugs,the drug properties were mostly warm and mild,the drug taste was mainly sweet,the drugs were mainly distributed in the five zang organs,with the kidney meridian being the first target.According to the re-sults of comprehensive data analysis,five core Chinese medicines(Wolfberry,ginseng,American ginseng,Astragalus,Poria)were screened out.A total of 105 active ingredients(corresponding to 219 target genes),1 568 aging-related potential targets,and 137 in-tersection targets were obtained.According to the degree value,12 core targets were screened out,mainly involving cancer pathways,lipids and atherosclerosis,AGE-RAGE and other signaling pathways.The results of molecular docking showed that the key anti-aging components could spontaneously and stably bind to the core targets.CONCLUSION Through data mining,network pharmacology and molecular docking,the prescription rules of anti-aging Chinese medicine health care prescriptions are analyzed,and the anti-ag-ing potential targets and mechanism pathways of five core traditional Chinese medicines are preliminarily revealed,so as to provide ref-erence and theoretical basis for delaying aging and preventing and treating related diseases in the elderly.

OBJECTIVE To explore the medication rule and potential mechanism of anti-aging traditional Chinese medicine health care prescription by using data mining,network pharmacology and molecular docking technology.METHODS By searching the special food information query platform of the State Administration for Market Regulation and Yaozhi.com,the health care prescrip-tions with traditional Chinese medicine as the main component and anti-aging effect were searched.The data mining technology was used to analyze the prescription rules,and the core anti-aging traditional Chinese medicine was selected according to the analysis re-sults.The chemical constituents and corresponding targets of core anti-aging traditional Chinese medicines were obtained by searching TCMSP and other databases;potential targets related to aging from GeneCards and OMIM databases were screened;the intersection tar-gets of core Chinese medicine and aging were obtained.Subsequently,protein-protein interaction(PPI)network analysis,gene ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using STRING database and Cytoscape 3.7.2 software.Finally,the affinity of core targets and key components was verified by molecular docking technology.RESULTS A total of 244 kinds of anti-aging traditional Chinese medicine health care prescriptions were screened and included.The prescription drugs were mainly tonic drugs,the drug properties were mostly warm and mild,the drug taste was mainly sweet,the drugs were mainly distributed in the five zang organs,with the kidney meridian being the first target.According to the re-sults of comprehensive data analysis,five core Chinese medicines(Wolfberry,ginseng,American ginseng,Astragalus,Poria)were screened out.A total of 105 active ingredients(corresponding to 219 target genes),1 568 aging-related potential targets,and 137 in-tersection targets were obtained.According to the degree value,12 core targets were screened out,mainly involving cancer pathways,lipids and atherosclerosis,AGE-RAGE and other signaling pathways.The results of molecular docking showed that the key anti-aging components could spontaneously and stably bind to the core targets.CONCLUSION Through data mining,network pharmacology and molecular docking,the prescription rules of anti-aging Chinese medicine health care prescriptions are analyzed,and the anti-ag-ing potential targets and mechanism pathways of five core traditional Chinese medicines are preliminarily revealed,so as to provide ref-erence and theoretical basis for delaying aging and preventing and treating related diseases in the elderly.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Adult ; Carcinoma, Neuroendocrine ; metabolism ; pathology ; surgery ; Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Chromogranin A ; metabolism ; Female ; Humans ; Keratin-7 ; metabolism ; Keratin-8 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Liver Neoplasms ; secondary ; Mixed Tumor, Malignant ; metabolism ; pathology ; surgery ; Nephrectomy ; Neprilysin ; metabolism ; Synaptophysin ; metabolism ; Vimentin ; metabolism