Pharmacology-based molecular docking of 4-methylcatechol and its role in RANKL-mediated ROS/Keap1/Nrf2 signalling axis and osteoclastogenesis.
Pharmacology-based molecular docking of 4-methylcatechol and its role in RANKL-mediated ROS/Keap1/Nrf2 signalling axis and osteoclastogenesis.
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DOI：
10.1016/j.biopha.2022.114101
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发表时间：
2023-01
期刊：
影响因子：
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通讯作者：
Yang Xu;Dezhi Song;Yuangang Su;Junchun Chen;Liwei Wu;Haoyu Lian;Na Hai;Jing Li;Jie Jiang-Jie-Jian
中科院分区：
文献类型：
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作者：
Yang Xu;Dezhi Song;Yuangang Su;Junchun Chen;Liwei Wu;Haoyu Lian;Na Hai;Jing Li;Jie Jiang-Jie-Jian
4-Methylcatechol (4-MC) is an agonist of various neurotrophic factors, which can upregulate the expression of Heme oxygenase 1 (HO-1) protein by activating nuclear factor erythroid 2-related factor 2 (Nrf2), thereby inhibiting oxidative stress-induced neural stem cell death. During RANKL-stimulated osteoclast differentiation, intracellular reactive oxygen species (ROS) levels were increased. Nonetheless, the effect of 4-MC on osteoclast formation and bone resorption function has not been researched. In this study, we investigated the effect of HO-1 upregulation by 4-MC on RANKL-induced osteoclastogenesis and explored the molecular mechanism of HO-1 upregulation by 4-MC. We found that the small molecule compound 4-MC could bind to Keap1 amino acid residue of glycine GLY 367, isoleucine ILE 559 and valine VAL 606, with a predicted binding energy of −4.99 kcal/mol. 4-MC was found to inhibit osteoclast differentiationin vitroby activating Nrf2 to scavenge ROS, inhibiting NF-κB phosphorylation, and alleviating osteoporosis in ovariectomized (OVX) mice. Taken together, 4-MC reduces ROS by inhibiting Keap1, thereby preventing OVX-induced bone loss.
