Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification

Ou, Li; Kang, W.; Liang, Zhijian; Gao, Feng; Dong, Taiwei; Wei, Peifeng; Li, Min

doi:10.1186/s13018-021-02751-5

Cited by 14 publications

(6 citation statements)

References 44 publications

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“…Luteolin belongs to the flavone family commonly present in plants. Studies have shown that both isolated luteolin and plant extracts have anti-inflammatory activity [38–39]. Luteolin-7-O-Glucuronide (L7Gn), an active component of luteolin, has been identified to prevent overproduction of inflammatory mediators including IL-6, IL-1β and cyclooxygenase 2 [40].…”

Section: Discussionmentioning

confidence: 99%

An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease

Zhu

Xue

et al. 2023

Preprint

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PurposeTo explore the possible pharmacological mechanisms of Danbai Granules (DBG) against sequelae of pelvic inflammatory disease (SPID) by the method of network pharmacology and molecular docking combined with experimental validation.MethodsFirstly, biologically active compounds, targets of DBG, and related targets of SPID were collected from public databases. The protein– protein interaction (PPI) network, Gene GO and KEGG enrichment analysis were carried out via R language to find the potential biological processes and pathways of DBG against SPID. Subsequently, molecular docking was used to calculate the affinity between the top six targets and the top ten compounds, respectively. Finally, the above analysis results were verified by in vivo experiments.ResultsA total of 106 crossover genes were selected from 220 potential medicine genes and 952 SPID-related genes. PPI network analysis indicated that IL-6, IL-1β, VEGFA, CASP3, PTGS2, JUN, etc., were core targets. GO and KEGG enrichment analysis revealed that PI3K-Akt, AGE–RAGE, IL-17, TNF, HIF-1 and Toll-like receptors signaling pathways were the main signaling pathways. Molecular docking showed that 15 pairs of target-ingredient combinations have good binding activity. The animal experiments showed that DBG administration inhibited the expression of TLR4/MyD88/NF-κB p65 signaling pathway-related proteins expression, altered the high expression of IL-6, IL-1β, and low level of IL-4, IL-10, thereby relieving the pelvic inflammation of SPID.ConclusionThrough the network pharmacology and molecular docking, our findings predicted the active ingredients and potential targets of DBG in treating SPID. The experimental verification preliminarily revealed that DBG may inhibit the inflammatory response of SPID rats by regulating the TLR4/MyD88/NF-κB p65 signaling pathway. which provides a theoretical basis for the study of the pharmacodynamic material basis and mechanism of DBG against SPID at the comprehensive level.

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Section: Discussionmentioning

confidence: 99%

An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease

Zhu

Xue

et al. 2023

Preprint

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“…Estrogen receptor 1(ESR1) is the host gene of hsa_circ_0078309, which is an estrogen receptor subtype widely expressed in bone tissue ( 82 ). Studies have illustrated that estrogen plays a role in regulating bone metabolism mainly by interacting with ESR1 ( 83 ). So, has_circRNA_0078309 may regulate bone metabolism of PMOP.…”

Section: Discussionmentioning

confidence: 99%

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

2022

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BackgroundOsteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network.MethodsThe PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed.ResultsA total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as “olfactory transduction”, “T cell receptor signaling pathway”, and “neuroactive ligand-receptor interaction”. These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways.ConclusionsA circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.

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“…Estrogen signaling pathway is essential for the development of OP. Estrogen is an important regulatory hormone in the human body, and its physiological role is mainly to regulate the transcription and translation of target genes by acting on the estrogen receptors of tissue cells 85 . As the major estrogen receptor subtype in bone tissue, ESR1 also plays an important role in regulating bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis

Wang

Fan

Feng

et al. 2022

Sci Rep

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Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein–protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson–Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

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Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification

Cited by 14 publications

References 44 publications

An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease

An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease

Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis

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