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Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Deng Wei[1,2,3] * ; Huang YanBo[1,2,3] ; Li HaiShang[1,2,3] ; Chen ChiWei[4] ; Lin YueWei[1,2,3] ; Wang Min[1,2,3] ; Huang HuaSheng[1,2,3] ; Liu Teng[1,2,3] ; Qin QiuLi[1,2,3] ; Shao Yang[1,2,3] ; Tang YongChao[1,2] ; Yuan Kai[1,2] ; Ding JinYong[1,2] ; Xu LiangLiang[1,2] ; Li YongXian[1,2] ; Zhang ShunCong[1,2] ;
机构： [1]The First Clinical Academy, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. [3]Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China. [4]Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
出处：
DOI： 10.3389/fphar.2022.1015693
ISSN：

关键词： dehydromiltirone osteoclastogenesis BMMS MAPK NF-κB network pharmacology

摘要：
Background: Osteoporosis is a type of systematic metabolic bone disease caused by the decrease in osteogenic activity or excessive resorption of bone with the relative enhancement of osteoclast function. As osteoporosis seriously affects the quality of patients' life, effective drugs are needed to treat this disease. Based on the combination of network pharmacology and cellular studies, this study aimed to investigate the probable mechanism of Dehydromiltirone (DHT) in the treatment of osteoporosis. Method: The targets of DHT in osteoporosis were searched using the PharmGKB, OMIM, and Genecard platforms. The PPI core targets, and the GO and KEGG enrichment analysis results were obtained using Cytoscape software, and the David and Metascape databases, respectively. The network pharmacology results were also verified via in vitro cellular experiments. Results: Through network pharmacology and docking analysis, we found DHT was involved in peptide tyrosine phosphorylation, cell surface receptor tyrosine kinase signaling pathways, and MAPK signaling pathways. According to the molecular docking results, the binding of DHT to MAPK14 was more stable than other proteins, which suggests that DHT may affect osteoclast formation through the MAPK signaling pathway. Moreover, DHT was found to inhibit the expression of osteoclast-associated genes, including NFATc1, CTSK, c-Fos, Acp5, and MMP9; as well as the phosphorylation of P38, ERK, and JNK of the MAPK signaling pathway; and the degradation of IκB-α of NF-κB signaling pathway. Conclusion: DHT exhibited an anti-osteoclastogenesis effect by reducing the expression of related genes, ultimately inhibiting bone resorption in vitro.Copyright © 2022 Deng, Huang, Li, Chen, Lin, Wang, Huang, Liu, Qin, Shao, Tang, Yuan, Ding, Xu, Li and Zhang.

基金：
Administration of Traditional Chinese Medicine of Guangdong Province, China (Number: 20203004; 20221146); Natural Science Foundation of Guangdong Province, China (Number: 2021A1515012168); Basic and Applied Basic Research Fund Project in Guangdong Province, China (Number: 2020A1515110948); Science and Technology Program of Guangzhou, China (Number: 202102021040). Innovation training program of Guangzhou University of Chinese Medicine (No. 202210572308; 202210572150).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 2 区 医学
小类 | 2 区 药学
最新[2025]版：
大类 | 3 区 医学
小类 | 3 区 药学
JCR分区：
出版当年[2020]版：
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]The First Clinical Academy, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. [3]Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, China.
通讯作者：
通讯机构： [1]The First Clinical Academy, Guangzhou University of Chinese Medicine, Guangzhou, China. [2]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
推荐引用方式(GB/T 7714)：
Deng Wei,Huang YanBo,Li HaiShang,et al.Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity[J].FRONTIERS IN PHARMACOLOGY.2022,13:doi:10.3389/fphar.2022.1015693.
APA：
Deng Wei,Huang YanBo,Li HaiShang,Chen ChiWei,Lin YueWei...&Zhang ShunCong.(2022).Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity.FRONTIERS IN PHARMACOLOGY,13,
MLA：
Deng Wei,et al."Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity".FRONTIERS IN PHARMACOLOGY 13.(2022)

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