Dataset Information

A study on the anti-osteoporosis mechanism of isopsoralen based on network pharmacology and molecular experiments.

ABSTRACT:

Objective

Osteoporosis (OP) is a disease caused by multiple factors. Studies have pointed out that isopsoralen (IPRN) is one of the most effective drugs for the treatment of OP. Based on network pharmacological and molecular experimental analysis, the molecular mechanism of IPRN in osteoporosis is clarified.

Methods

IPRN target genes and OP-related genes were predicted from the databases. Intersections were obtained and visualized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on target genes, which was confirmed by experiments internal and external experiments. Molecular docking was used to verify the binding between IPRN and target proteins. Molecular dynamics (MD) simulates the binding affinity of protein targets and active compounds.

Results

87 IPRN target genes and 242 disease-related targets were predicted. The protein-protein interaction (PPI) network identified 18 IPRN target proteins for the treatment of OP. GO analysis indicated that target genes were involved in biological processes. KEGG analysis showed that pathways such as PI3K/AKT/mTOR were associated with OP. Cell experiments (qPCR and WB) found that the expressions of PI3K, AKT, and mTOR in MC3T3-E1 cells at 10 μM, 20 μM, and 50 μM IPRN concentrations, especially at 20 μM IPRN treatment, were higher than those in the control group at 48 h. Animal experiments also showed that compared with the control group, 40 mg/kg/time IPRN could promote the expression of the PI3K gene in chondrocytes of SD rats.

Conclusions

This study predicted the target genes of IPRN in the treatment of OP and preliminarily verified that IPRN plays an anti-OP role through the PI3K/AKT/mTOR pathway, which provides a new drug for the treatment of OP.

SUBMITTER: Wang J

PROVIDER: S-EPMC10108469 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A study on the anti-osteoporosis mechanism of isopsoralen based on network pharmacology and molecular experiments.

Wang Jian J Chen Tianyu T Li Xiang X Zhang Yu Y Fu Shuang S Huo Ruikun R Duan Yan Y

Journal of orthopaedic surgery and research 20230417 1

<h4>Objective</h4>Osteoporosis (OP) is a disease caused by multiple factors. Studies have pointed out that isopsoralen (IPRN) is one of the most effective drugs for the treatment of OP. Based on network pharmacological and molecular experimental analysis, the molecular mechanism of IPRN in osteoporosis is clarified.<h4>Methods</h4>IPRN target genes and OP-related genes were predicted from the databases. Intersections were obtained and visualized. Gene Ontology (GO) and Kyoto Encyclopedia of Gene ...[more]

PMID: 37069639

Similar Datasets

Project description:Xianlinggubao formula (XLGB), is a traditional Chinese compound Medicine that has been extensively used in osteoarthritis and aseptic osteonecrosis, but its curative effect on diabetic osteoporosis (DOP) and its pharmacological mechanisms remains not clear. The aim of the present study was to investigate the possible mechanism of drug repurposing of XLGB in DOP therapy. We acquired XLGB active compounds from the traditional Chinese medicine systems pharmacology and traditional Chinese medicines integrated databases and discovered potential targets for these compounds by conducting target fishing using the traditional Chinese medicine systems pharmacology and Swiss Target Prediction databases. Gene Cards and Online Mendelian Inheritance in Man® database were used to identify the DOP targets. Overlapping related targets between XLGB and DOP was selected to build a protein-protein interaction network. Next, the Metascape database was utilized to enrich the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. In addition, Auto-Dock Vina software was used to verify drug and target binding. In total, 48 hub targets were obtained as the candidate targets responsible for DOP therapy. The anti-DOP effect mediated by XLGB was primarily centralized on the advanced glycation end products (AGEs)-receptor for AGE signaling pathway in diabetic complications and osteoclast differentiation. In addition, AKT serine/threonine kinase 1, tumor necrosis factor, Interleukin-6, vascular endothelial growth factor A and peroxisome proliferator activated receptor gamma, which were considered as potential therapeutic targets. Furthermore, molecular docking results confirm the credibility of the predicted therapeutic targets. This study elucidates that XLGB may through regulating AGEs formation and osteoclast differentiation as well as angiogenesis and adipogenesis against DOP. And this study provides new promising points to find the exact regulatory mechanisms of XLGB mediated anti-DOP effect.

Project description:BackgroundThe purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification.MethodsThe SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. "R" language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting.ResultsA total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells.ConclusionSAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway.

Project description:Background and Aim: QingXiaoWuWei Decoction (QXWWD) is a traditional Chinese medicine that is commonly used in clinical settings to treat inflammatory and bacterial diseases. However, there is still a lot to learn about its molecular mechanism. A network pharmacology approach was applied to investigate the pharmacological mechanisms of QXWWD in inflammation treatment. Methods: The basic mechanisms involved in the anti-inflammatory and antibacterial potentials of QXWWD were identified using network pharmacology and molecular docking. The principal components of QXWWD were identified by the HPLC-Q-Exactive-MS method. The antibacterial bioactivity of QXWWD was further investigated using the Kirby-Bauer disc diffusion method and the determination of the minimum inhibitory concentration. The anti-inflammatory activity of QXWWD was evaluated using mice ear swelling test, RAW264.7 cell culture, and pro-inflammatory cytokines measurement. Skin irritation and HE staining were employed to evaluate the safety of QXWWD topical use and to depict the drug's potential therapeutic function. The hub genes and signaling pathways associated with inflammatory and bacterial diseases were validated by western blot in addition to biochemical and pathological markers. Results: Our findings revealed that the ethanolic extract of QXWWD had a strong inhibitory effect against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae. Meanwhile, QXWWD was potentially effective in suppressing ear swelling, elevated white blood cell counts, and the TNF-α, IL-1, and IL-6 levels. According to skin irritation, QXWWD was found to be safe when tested for topical application. The results of HE staining showed that the possible therapeutic role of QXWWD was related to the change in skin microstructure. Also, the network pharmacology, molecular docking as well as Q-Exactive-MS and HPLC analysis suggested that the synergistic effect of quercetin, luteolin and other ingredients could serve as main contributor of QXWWD for its anti-inflammatory and antibacterial activities. Moreover, the JUN, MAPK1, RELA, NFKBIA, MYC, and AKT1 were the potential identified key targets, and MAPK/PI3K/Akt was among the possibly involved signaling pathways in the anti-inflammatory and antibacterial activities of QXWWD. Conclusions: From a therapeutic standpoint, QXWWD may be a promising antibacterial and anti-inflammatory agent for the treatment of bacterial, acute, and chronic dermatitis.

Project description:As the society is aging, the increasing prevalence of osteoporosis has generated huge social and economic impact, while the drug therapy for osteoporosis is limited due to multiple targets involved in this disease. Zhuangguguanjie formulation (ZG) is extensively used in the clinical treatment of bone and joint diseases, but the underlying mechanism has not been fully described. This study aimed to examine the therapeutic effect and potential mechanism of ZG on postmenopausal osteoporosis. The ovariectomized (OVX) mice were treated with normal saline or ZG for 4 weeks after ovariectomy following a series of analyses. The bone mass density (BMD) and trabecular parameters were examined by micro-CT. Bone remodeling was evaluated by the bone histomorphometry analysis and ELISA assay of bone turnover biomarkers in serum. The possible drug-disease common targets were analyzed by network pharmacology. To predict the potential biological processes and related pathways, GO/KEGG enrichment analysis was performed. The effects of ZG on the differentiation phenotype of osteoclasts and osteoblasts and the predicted pathway were verified in vitro. The results showed that ZG significantly improved the bone mass and micro-trabecular architecture in OVX mice compared with untreated OVX mice. ZG could promote bone formation and inhibit bone resorption to ameliorate ovariectomy-induced osteoporosis as evidenced by increased number of osteoblast (N.Ob/Tb.Pm) and decreased number of osteoclast (N.Oc/Tb.Pm) in treated group compared with untreated OVX mice. After identifying potential drug-disease common targets by network pharmacology, GO enrichment analysis predicted that ZG might affect various biological processes including osteoblastic differentiation and osteoclast differentiation. The KEGG enrichment analysis suggested that PI3K/Akt and mTOR signaling pathways could be the possible pathways. Furthermore, the experiments in vitro validated our findings. ZG significantly down-regulated the expression of osteoclast differentiation markers, reduced osteoclastic resorption, and inhibited the phosphorylation of PI3K/Akt, while ZG obviously up-regulated the expression of osteogenic biomarkers, promoted the formation of calcium nodules, and hampered the phosphorylation of 70S6K1/mTOR, which can be reversed by the corresponding pathway activator. Thus, our study suggested that ZG could inhibit the PI3K/Akt signaling pathway to reduce osteoclastic bone resorption as well as hamper the mTORC1/S6K1 signaling pathway to promote osteoblastic bone formation.

Project description:BackgroundWith the advent of ageing population, osteoporosis (OP) has already become a global challenge. Jintiange capsule is extensively applied to treat OP in China. Although recent studies demonstrate that it generates significant effects on strengthening bone, the exact mechanism of the jintiange capsule for treating OP remains unknown.PurposeTo understand the main ingredients of the jintiange capsule, predict the possible targets and the relevant signal transduction pathways, and explore the mechanism of the jintiange capsule for the treatment of OP.MethodsMain ingredients of the jintiange capsule, drug targets, and potential disease targets for OP were obtained from public databases. Molecular biological processes and signaling pathways were determined via bioinformatic analysis, containing protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the disease-drug-ingredient-targets-pathways networks were constructed using Cytoscape. According to CytoNCA, core targets were acquired. Finally, the present study conducted molecular docking for better testing the abovementioned results.ResultsIn the current work, we found that 4 main ingredients of the jintiange capsule, 33 drug targets, 4745 potential disease targets for OP, and 12 overlapping targets were identified. PPI network containing 12 nodes and 25 edges proved that there existed a complex relationship. As revealed by GO functional annotation, the intersected targets were mostly associated with BP, CC, and MF. The targets were enriched to 368 items in BP, 27 items in CC, and 42 items in MF. They mainly included calcium ion homeostasis, calcium channel complex, and calcium channel regulator activity. According to KEGG pathway analysis, the intersected targets were mostly associated with Rap 1, cGMP-PKG, Ras, cAMP, calcium pathways, and so on. Based on the analysis with CytoNCA, we acquired 4 core targets, respectively-CALR, SPARC, CALM1, and CALM2. Besides, 2 core targets, CALR and CALM1, were selected for molecular docking experiments. Molecular docking revealed that the main ingredient, calcium phosphate, had good binding with the CALR protein and CALM1 protein.ConclusionTo conclude, the main ingredient of the jintiange capsule, particularly calcium phosphate, may interact with 2 targets, CALR and CALM1, and regulate multiple signaling pathways to treat OP. Additionally, this also benefits us in further understanding the mechanism of the jintiange capsule for treating OP.

Dataset Information

A study on the anti-osteoporosis mechanism of isopsoralen based on network pharmacology and molecular experiments.

Objective

Methods

Results

Conclusions

Publications

A study on the anti-osteoporosis mechanism of isopsoralen based on network pharmacology and molecular experiments.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets