Network pharmacology-based mechanism prediction and pharmacological validation of Bushenhuoxue formula attenuating postmenopausal osteoporosis in ovariectomized mice

Xia, Chenjie; Zhu, Haowei; Jin, Li; Jin, Hongting; Fu, Danqing

doi:10.1186/s13018-023-03696-7

Cited by 5 publications

(5 citation statements)

References 44 publications

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“…Here, OB ≥ 30% and DL ≥ 0.18 were set as the screening filters to identify the active ingredients of Lycii Fructus. [ 26 ] Then, we obtained the active ingredient-related targets by using the computer targeting technology contained in the TCMSP, and further transformed the target name to a standard gene symbols in the Uniport database ( https://www.uniprot.org/ ) with the filters of “swiss-prot reviewed” and “Homo sapiens.”…”

Section: Methodsmentioning

confidence: 99%

“…DisGeNET database ( https://www.disgenet.org/ ) and GeneCards database ( https://www.genecards.org/ ) were used to select targets associated with PMOP. Through inputting “postmenopausal osteoporosis” and further screening with the filters of score > 0.1 in DisGeNET and score > 10 in GeneCards, [ 26 ] a total of 292 PMOP-related targets were finally obtained.…”

Section: Methodsmentioning

confidence: 99%

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Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis

Wang,

et al. 2023

Medicine

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Postmenopausal osteoporosis (PMOP) has become one of most frequent bone diseases worldwide with aging population. Lycii Fructus, a common plant fruit with the property of drug homologous food, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of Lycii Fructus against PMOP through using network pharmacology approach. The active ingredients of Lycii Fructus were obtained from Traditional Chinese Medicine System Pharmacology database. Target fishing was performed on these ingredients in UniProt database for identification of the relative targets. Then, we screened the targets related to PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and Lycii Fructus were obtained to perform protein–protein interaction, gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis. A total of 35 active ingredients were identified in Lycii Fructus, and fished 158 related targets. Simultaneously, 292 targets associated with PMOP were obtained from GeneCards database and DisGeNET database. By drawing Venn diagram, 41 overlapping genes were obtained, and were considered as therapeutically relevant. Gene ontology enrichment analysis predicted that anti-inflammation and promotion of angiogenesis might be 2 potential mechanism of Lycii Fructus for PMOP treatment. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as IL-17 pathway, TNF pathway, MAPK pathway, PI3K-Akt signaling pathway and HIF signaling pathway were involved in regulating these 2 biological processes. Through the method of network pharmacology, we systematically investigated the mechanisms of Lycii Fructus against PMOP. The identified multi-targets and multi-pathways provide new insights to further determinate its exact pharmacological mechanisms.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis

Wang,

et al. 2023

Medicine

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“…Meanwhile, we searched the Disgenet database (https://www.disgenet.org/) and GeneCards (https://www.genecards.org) with "Rosacea" as the keyword, and screened the results with the following criteria: score > 0.1 in DisGeNET and score > 10 in GeneCards. [7] We merged the screening results with DEGs as rosacea-related targets. We constructed Venn diagrams on the jvenn JavaScript library [8] to identify overlapping target genes between LXWHT and Rosacea for further bioinformatics analyses.…”

Section: Screening Of Rosacea-related Targetsmentioning

confidence: 99%

Exploring the mechanism of Liang Xue Wu Hua Tang in the treatment of rosacea via network pharmacology and molecular docking

Cui,

Fan

2024

Medicine

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Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein–protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.

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“…Bushenhuoxue (BSHX) formula is a traditional herbal decoction composed of nine herbs (listed in S1 Table ). It has been widely used to treat various bone diseases in China for several decades [ 7 ]. According to TCM syndromes, the deficiency and blood stasis are regarded as the main pathogenesis of OA [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

BushenHuoxue formula promotes osteogenic differentiation via affecting Hedgehog signaling pathway in bone marrow stem cells to improve osteoporosis symptoms

Chen,

Wei,

Shi

et al. 2023

PLoS ONE

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Background The BushenHuoxue formula (BSHX) has been previously demonstrated to ameliorate osteoporosis, but the mechanisms underlying this phenomenon are currently unclear. The present study aims at investigating the mechanisms that BSHX induces osteogenesis. Methods We established an osteoporosis model in rats by bilateral ovariectomy and then treated the rats with an osteogenic inducer (dexamethasone, β-sodium glycerophosphate and Vitamin C) and BSHX. After that, bone marrow density and histopathological bone examination were evaluated by using HE staining and immunohistochemistry, respectively. We also assessed the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts by using immunofluorescence staining. ALP, BMP, and COL1A1 levels were determined by ELISA. We identified genes involved in pathogenesis of osteoporosis through Gene Expression Omnibus (GEO) database and subsequently selected Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2 for assessment via qRT-PCR and ELISA, Western blotting. Network pharmacology analysis was performed to identify bioactive metabolites of BSHX. Results BSHX treatment in osteoporosis model rats promoted tightening of the morphological structure of the trabecular bone and increased the bone mineral density (BMD). BSHX also increased levels of osteoblast makers ALP, BMP, and COL1A1. Additionally, bioinformatics analysis of the GEO dataset showed that Hedgehog signaling pathway was involved in pathogenesis of osteoporosis, especially related genes Shh, Ihh, Gli2, and Runx2. Remarkably, BHSX upregulated these genes indispensably involved in the osteogenesis-related Hedgehog signaling pathway in both bone tissue and BMSCs. Importantly, we identified that quercetin was the active compounds that involved in the mechanism of BSHX-improved OP via affecting Hedgehog-related genes. Conclusion Our results indicate that BSHX promotes osteogenesis by improving BMSC differentiation into osteoblasts via increased expression of Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2, and quercetin was the bioactive compound of BSHX.

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Network pharmacology-based mechanism prediction and pharmacological validation of Bushenhuoxue formula attenuating postmenopausal osteoporosis in ovariectomized mice

Cited by 5 publications

References 44 publications

Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis

Network pharmacology-based pharmacological mechanism prediction of Lycii Fructus against postmenopausal osteoporosis

Exploring the mechanism of Liang Xue Wu Hua Tang in the treatment of rosacea via network pharmacology and molecular docking

BushenHuoxue formula promotes osteogenic differentiation via affecting Hedgehog signaling pathway in bone marrow stem cells to improve osteoporosis symptoms

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