Post-menopausal osteoporosis (PMOP) is associated with estrogen deficiency and worldwide, is becoming increasingly more prevalent in aging women. Various anti-PMOP drugs have been developed to reduce the burden of PMOP; generally, these drugs are efficacious, but with some adverse side effects. Tubson-2 decoction (TBD), a popular traditional Mongolian medicine, has been used to treat PMOP for centuries. However, the precise mechanisms underlying the action of TBD on PMOP have yet to be fully elucidated. Herein, we combined network pharmacology with untargeted metabolomics to identify the key targets and metabolic pathways associated with the interventional effects of TBD on ovariectomized (OVX) rats. Furthermore, we investigated the bone histomorphometry of eight different groups of rats to evaluate the therapeutic effect of TBD. First, we established a TBD-target/PMOP network via network pharmacology; this network identified three key protein targets—vitamin D receptor (VDR), cytochrome P450 19A1 (CYP19A1), and 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1). Morphological analysis showed that severe impairment of the bone micro-architecture in OVX rats could be improved by TBD administration. The TBD-treated rats had a significantly lower bone surface-to-tissue volume (BS/TV) and a significantly smaller trabecular separation (Tb·Sp.) ( P <0.05) than the OVX rats; in contrast, bone volume fraction (BVF), trabecular thickness (Tb·Th.), trabecular number (Tb·N.), and bone mineral density (BMD) were significantly higher in the TBD-treated rats ( P <0.05). Multivariate and univariate analysis showed that OVX resulted in significant alterations in the concentrations of 105 metabolites and 11 metabolic pathways (P<0.05); in addition, 26 potential biomarkers were identified to investigate the progression of PMOP. Network pharmacology showed that major alterations in vitamin B6 metabolism were associated with the VDR target. Next, we validated the three crucial targets (VDR [P<0.01], HSD11B1 [P<0.01], and CYP19A1 [P<0.05]) by enzyme-linked immunosorbent assays (ELISAs) and demonstrated that the levels of these targets were elevated in the OVX group but reduced in the TBD-treatment group. Collectively, our results suggest that the interventional effects of TBD on OVX rats are likely to be associated with the down regulation of VDR. Our findings enhance our molecular understanding of the interventional effects of TBD on PMOP and will allow us to develop further TBD studies.
The aim of the study is to determine the target of Paeteria scandens in nonalcoholic fatty liver disease ( NAFLD ). The Chinese herbal medicine pharmacology data and analysis platform were used to search and screen for the effective components of the Paeteria scandens compounds and to analyze the possible therapeutic targets based on network topology. In addition, various known disease target databases were enrolled, the therapeutic target proteins in NAFLD were screened, and a protein–protein interaction network was constructed. Enrichment analysis was performed on key nodes. Finally, the inhibitory effect of Paeteria scandens on NAFLD was verified by experiments. We identified 33 major candidate targets of Paeteria scandens and successfully constructed a “drug-compound-target-disease” network. Abovementioned targets revealed by gene enrichment analysis have played a significant role in the cell cycle, apoptosis, and related signal pathways. We demonstrated that Paeteria scandens downregulated serum triglyceride and lipopolysaccharides levels in NAFLD chickens by feeding with a high-capacity diet and endotoxin of Salmonella enteritidis was given by gavage. Paeteria scandens may regulate the hepatic cell cycle and apoptosis through the Salmonella infection pathway, Toll-like receptor signaling pathway, and apoptosis pathway. For NAFLD, Paeteria scandens may be a promising, long-lasting treatment strategy.
Background: Compound Danshen Dropping Pills (CDDP) is widely used in clinical treatment of epilepsy. But the underlying active ingredients and molecular mechanisms are unclear. Our study aims to investigate the active components and functional mechanisms of CDDP in treating epilepsy using a network pharmacology approach.Methods: Candidate constituents and targets of CDDP were searched on the Traditional Chinese Medicine Systems Pharmacology database. NCBI and Genecards were used to establish a database of epilepsy targets.Next, used Cytoscape software, the interactive network diagram of "drug-active component-target" was drawn. Based on the STRING database we constructed protein-protein interaction network and analyzed protein-protein interaction relationships. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the common targets. Molecular docking provided an evaluation tool for verifying the combination of components and targets, which was performed using Auto-dock.Results: Sixty bioactive components, corresponding to 79 therapeutic targets for epilepsy, were successfully identified. Functional enrichment analysis showed that CDDP plays a pharmacological role in the treatment of epilepsy by regulating serotonergic synapses, morphine addiction, nicotine addiction and other pathways, as well as the NF-κB signaling pathway. Molecular docking analysis showed that representative components may be closely bound to key targets.Conclusions: This network pharmacology study revealed the synergistic effects of multiple components, targets, and pathways of CDDP in the treatment of epilepsy, which will deepen our understanding of the underlying molecular mechanisms of CDDP in the treatment of epilepsy and lay the foundation for further experimental studies.
Background and objective: Alzheimer's Disease (AD) is considered as a progressively developing neurodegenerative disease with an insidious onset that induces increased cost of social burden and decreased quality of life. Acoritataninowii Rhizoma produced the effects of resuscitating and eliminating phlegm, dispelling dampness and appetizing, refreshing mind and nourishing the mind, and exerted the activities of anti-dementia and improving learning and memory. while little was relevant to its anti-AD mechanism. The present study explored the potential mechanism of Acoritataninowii Rhizoma defend AD by network pharmacology and molecular docking.Methods: The bioactive ingredients of Acoritataninowii Rhizoma were screened by absorption, distribution, metabolism as well as excretion evaluation and obtained from databases retrieval. Genes associated with AD or ingredients were searching by databases, and the overlapping genes between AD and ingredients were analyzed by the Venn diagram. Moreover, the network of Acoritataninowii Rhizoma-ingredients-targets-AD was visualized by cytoscape software. Furthermore, protein-protein interaction, gene ontology, pathway enrichment and molecular docking were conducted to evaluate potential factors of Acoritataninowii Rhizoma against AD.Results: 4 potential compounds were considered as bioactive ingredients after screening ADME. 81 ingredients-related genes and 6765 AD-related genes were screened by databases with 61 overlapping genes. The bioactive ingredients derived from Acoritataninowii Rhizoma (e.g Cycloartenol, (1R,3aS,4R,6aS)-1,4bis (3,4-dimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[4,3-c]furan, 8-Isopentenyl-kaempferol, kaempferol) and target proteins (e.g AKT1, JUN, ESR1, CASP3, MAPK14, RELA) with high degree in the network were associated with in mitogen-activated protein kinase (MAPK) of DNA-binding transcription factor.Moreover, Acoritataninowii Rhizoma might play a signi cant in the treatment of AD which induced Fluid shear stress and atherosclerosis, Kaposi sarcomaassociated herpesvirus infection, Epstein-Barr virus infection, AGE-RAGE signaling pathway in diabetic complications. Conclusion:The bioactive ingredients and potential mechnism of Acoritataninowii Rhizoma defended AD was analyzed by network pharmacology and molecular docking. This study provided a research basis and scienti c evidence for supporting the activities of Acoritataninowii Rhizoma against AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.