Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

Yu, Yunfeng; Liu, Xi; Yin, Shuang; Hu, Gang; Yang, Xinyu; Wei-xiong, Jian; Yu, Rong

doi:10.3389/fphar.2023.1147360

Cited by 2 publications

(1 citation statement)

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“…According to the chemical name "regorafenib" and the CAS number "755037-03-7″, the structural formula was obtained by searching the PubChem database 29 (https://pubchem.ncbi.nlm.nih.gov/). Subsequently, related targets for regorafenib were identified from the Swiss Target Prediction database, 30 the PharmMapper database (http://www.lilab-ecust.cn/pharmmapper/), and the Comparative Toxicogenomics Database 31 (CTD, https:// ctdbase.org/). Finally, gene names were normalized based on the species "Homo sapiens" in the UniProt database 32 (https:// www.uniprot.org/).…”

Section: Screening Potential Targets Of Regorafenib Andmentioning

confidence: 99%

Regorafenib Attenuates Osteoclasts Differentiation by Inhibiting the NF-κB, NFAT, ERK, and p38 Signaling Pathways

Zhou,

Su,

Luo

et al. 2024

ACS Omega

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Osteolytic diseases such as osteoporosis and neoplastic bone metastases are caused by the excessive activation of osteoclasts. Inhibiting the excessive activation of osteoclasts is a crucial strategy for treating osteolytic diseases. This study investigated the roles and mechanisms of regorafenib, a tyrosine kinase inhibitor, on osteoclasts and osteolytic diseases. We first identified the potential targets and mechanisms of regorafenib on osteoclast-related osteolytic diseases using network pharmacological analysis and molecular docking techniques. Then, we verified its role and mechanism on osteoclasts via cellular and animal experiments. Network pharmacology analysis identified 89 common targets shared by regorafenib and osteoclast-related osteolytic diseases. Enrichment analysis suggested that regorafenib may act on osteoclast-related osteolytic diseases by modulating targets such as AKT1, CASP3, MMP9, and MAPK3, regulating biological processes such as cell proliferation, apoptosis, and phosphorylation regulation, and influencing signaling pathways such as MAPK, PI3K/AKT, and osteoclast differentiation. The molecular docking results indicated that regorafenib and AKT1, CASP3, MMP9, MAPK3, and MAPK14 were stably docked. Cell experiments demonstrated that regorafenib significantly inhibited osteoclast differentiation and bone resorption in RAW 264.7 cells and bone marrow macrophages in a dose-dependent manner, with up to 50% reduction at 800 nM concentration without exhibiting cytotoxic effects. Furthermore, Western blot and RT-qPCR results demonstrated that regorafenib inhibited osteoclast differentiation by blocking the transduction of RANKL-induced NF-κB, p38, ERK, and NFAT signaling pathways. In vivo studies using an ovariectomized mouse model showed that regorafenib significantly improved bone volume fraction (BV/TV), bone surface to total volume (BS/TV), and number of trabeculae (TB.N), as well as reduced trabecular separation (Tb.Sp) compared to the OVX groups (P < 0.05). TRAcP staining results revealed a reduction in the number of osteoclasts with regorafenib treatment (P < 0.01). These results indicate that regorafenib exerts its protective effects against osteoclast-related osteolytic disease by inhibiting the RANKL-induced NF-κB, NFAT, ERK, and p38 signaling pathways. This study proves that regorafenib may serve as a potential therapeutic agent for osteoclast-related osteolytic diseases.

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Section: Screening Potential Targets Of Regorafenib Andmentioning

confidence: 99%