Deciphering the Underlying Mechanism of Eucommiae Cortex against Osteoporotic Fracture by Network Pharmacology

Shuai, Yongming; Jiang, Zhili; Yuan, Qiuwen; Tu, Shuqiang; Zeng, Fanhui

doi:10.1155/2020/7049812

Cited by 7 publications

(6 citation statements)

References 68 publications

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“…Mi et al [35] displayed that miR-7223-5p suppressed proliferation and fostered apoptosis of osteoblasts via targeting PIK3R1. Shuai et al [36] displayed that PIK3R1 may be a key target of Eucommiae Cortex for osteoporosis by network pharmacology. As such, our findings revealed that downregulation of PIK3R1 is associated with decreased proliferation and augmented apoptosis of osteoblasts, while its upregulation has an opposite effect.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Zhu

Chen

Ding

et al. 2021

Computational and Mathematical Methods in Medicine

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In an effort to bolster our understanding of regulation of bone formation in the context of osteoporosis, we screened out differentially expressed genes in osteoporosis patients with high and low bone mineral density by bioinformatics analysis. PIK3R1 is increasingly being nominated as a pivotal mediator in the differentiation of osteoblasts and osteoclasts that is closely related to bone formation. However, the specific mechanisms underlying the way that PIK3R1 affects bone metabolism are not fully elucidated. We intended to examine the potential mechanism by which PIK3R1 regulates osteoblast differentiation. Enrichment analysis was therefore carried out for differentially expressed genes. We noted that the estrogen signaling pathway, TNF signaling pathway, and osteoclast differentiation were markedly associated with ossification, and they displayed enrichment in PIK3R1. Based on western blot, qRT-PCR, and differentiation analysis in vitro, we found that upregulation of PIK3R1 enhanced osteoblastic differentiation, as evidenced by increased levels of investigated osteoblast-related genes as well as activities of ALP and ARS, while it notably decreased levels of investigated osteoclast-related genes. On the contrary, downregulation of PIK3R1 decreased levels of osteoblast-related genes and increased levels of osteoclast-related genes. Besides, in vitro experiments revealed that PIK3R1 facilitated proliferation and repressed apoptosis of osteoblasts but had an opposite impact on osteoclasts. In summary, PIK3R1 exhibits an osteoprotective effect via regulating osteoblast differentiation, which can be represented as a promising therapeutic target for osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Zhu

Chen

Ding

et al. 2021

Computational and Mathematical Methods in Medicine

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“…e bioactive ingredients and potential targets of five herbs in WSP were obtained in the online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM, http://bionet.ncpsb.org.cn/batmantcm/) database [25]. e screening conditions were set at a score cutoff � 20, p < 0.05 [26,27]. BATMAN-TCM is a bioinformatics analysis tool for the molecular mechanism of TCM with abundant herb-ingredient-targetdisease association information and integration analyses of targets, which can help researchers comprehensively and systematically understand the ingredients and targets of TCM preparations.…”

Section: Step 1: Prediction Of Wsp In the Treatment Of Goutmentioning

confidence: 99%

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Lang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Gout is a common crystal-related arthritis caused by the deposition of monosodium urates (MSU). Tibetan medicine Wuwei Shexiang Pills (WSP) has been demonstrated to exhibit anti-inflammatory, antihyperuricemia, and antigout activities. However, the underlying mechanism is unknown. Objectives. To explore the mechanisms of Wuwei Shexiang Pills on gouty arthritis via network pharmacology, molecule docking, and pharmacological verification. Methods. The ingredients and targets of WSP were obtained by searching and screening in BATMAN-TCM and SwissADME. The targets involving the gout were acquired from public databases. The shared targets were put onto STRING to construct a PPI network. Furthermore, Metascape was applied for the GO and KEGG enrichment analysis to predict the biological processes and signaling pathways. And molecular docking was performed to validate the binding association between the key ingredients and the relative proteins of TNF signaling. Based on the serum pharmacology, the predicted antigout mechanism of WSP was validated in MSU-induced THP-1 macrophages. The levels of inflammatory cytokines and mRNA were measured by ELISA and qRT-PCR, respectively, and MAPK, NF-κB, and NLRP3 signaling-associated proteins were determined by western blot and immunofluorescence staining. Results. 48 bioactive ingredients and 165 common targets were found in WSP. The data showed that 5-Cis-Cyclopentadecen-1-One, 5-Cis-Cyclotetradecen-1-One, (−)-isoshyobunone, etc. were potential active ingredients. TNF signaling, HIF-1 signaling, and Jak-STAT signaling were predicted to be the potential pathways against gout. The molecule docking analysis found that most ingredients had a high affinity for p65, NLRP3, IL-1β, TNF-α, and p38. The data from in vitro experiment showed that WSP suppressed the production and gene expression of inflammatory cytokines. Furthermore, WSP could inhibit the activation of MAPK, NF-κB, and NLRP3 signaling pathways. Conclusion. Our finding suggested that the antigout effect of WSP could be achieved by inhibiting MAPK, NF-κB, and NLRP3 signaling pathways. WSP might be a candidate drug for gouty treatment.

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“…[17] Bioinformatics, which includes herbal network pharmacology, continues to use an a priori analytical method to investigate the connections between medications, chemicals, disorders, and targets. [18] Network pharmacology is frequently used to clarify the mechanism of action of herbal medicines since it has the ability to analyze multiple components, multiple targets, and multiple pathways of herbal medicines, giving researchers new ideas and approaches. In order to identify the essential genes and pathways of DHJSD for the treatment of IVDD, as well as the active DHJSD compounds, we will apply the network pharmacology technique in this study.…”

Section: Introductionmentioning

confidence: 99%

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

et al. 2023

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Background: The purpose of this study was to examine the mechanism of Duhuo Jisheng Decoction (DHJSD) in the treatment of intervertebral disc degeneration (IVDD). Methods: The active compounds of DHJSD and their corresponding targets were obtained from the TCMSP database. “Intervertebral disc degeneration” was used as a search term in the DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards database to obtain disease-related targets. Following the discovery of overlapping DHJSD and IVDD targets, enrichment analyses for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways were performed. Cytoscape 3.9.1 was used to build the “DHJSD-Active Ingredients-Target Genes-IVDD” network and protein-protein interaction network, and CytoHubba was used to screen the pivotal genes. Molecular docking confirmed the binding activity of hub genes and key components. Results: The bioinformatic analysis of DHJSD in the treatment of IVDD revealed 209 potential therapeutic gene targets, including 36 important gene targets and 10 of these crucial gene targets. Enrichment analysis of 36 key therapeutic targets showed that the biological processes involved in the Gene Ontology analysis of DHJSD in treating IVDD were mainly cytokine-mediated signaling pathway, inflammatory response, negative regulation of apoptotic process, and vascular endothelial growth factor production. The Kyoto Encyclopedia of Genes and Genomes signaling pathway is mainly involved in TNF signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and HIF-1 signaling pathway. The Recactome signaling pathway is mainly involved in cytokine signaling in immune system, cellular responses to stress, immune system, cytokines, and inflammatory response. HIF1A and PPARG regulation of glycolysis are mostly involved in the WikiPathways signaling system. The findings demonstrated that to cure IVDD, DHJSD affects the pathogenic processes of inflammation, extracellular matrix, cellular senescence, autophagy, apoptosis, focal death, and proliferation through the aforementioned targets and signaling pathways. The results of molecular docking demonstrated that the protein can be effectively bound by the DHJSD active component. Further evidence was provided for the molecular mechanism through which DHJSD works to treat IVDD. Conclusion: This study uncovers the multi-component, multi-target, and multi-pathway characteristics of DHJSD for the treatment of IVDD, offering fresh perspectives to further investigate the mechanism of DHJSD for the treatment of IVDD.

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Deciphering the Underlying Mechanism of Eucommiae Cortex against Osteoporotic Fracture by Network Pharmacology

Cited by 7 publications

References 68 publications

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

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