Frontiers in Pharmacology (Sep 2022)

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

  • Wei Deng,
  • Wei Deng,
  • Wei Deng,
  • YanBo Huang,
  • YanBo Huang,
  • YanBo Huang,
  • HaiShang Li,
  • HaiShang Li,
  • HaiShang Li,
  • ChiWei Chen,
  • YueWei Lin,
  • YueWei Lin,
  • YueWei Lin,
  • Min Wang,
  • Min Wang,
  • Min Wang,
  • HuaSheng Huang,
  • HuaSheng Huang,
  • HuaSheng Huang,
  • Teng Liu,
  • Teng Liu,
  • Teng Liu,
  • QiuLi Qin,
  • QiuLi Qin,
  • QiuLi Qin,
  • Yang Shao,
  • Yang Shao,
  • Yang Shao,
  • YongChao Tang,
  • YongChao Tang,
  • Kai Yuan,
  • Kai Yuan,
  • JinYong Ding,
  • JinYong Ding,
  • LiangLiang Xu,
  • LiangLiang Xu,
  • YongXian Li,
  • YongXian Li,
  • ShunCong Zhang,
  • ShunCong Zhang

DOI
https://doi.org/10.3389/fphar.2022.1015693
Journal volume & issue
Vol. 13

Abstract

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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.

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