Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 159, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.114101
Keywords
4-Methylcatechol; Nrf2; Keap1; Osteoclast
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4-Methylcatechol activates Nrf2 to upregulate HO-1 expression, inhibits osteoclast differentiation, scavenges ROS, and alleviates osteoporosis in OVX mice.
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 differentiation in vitro by activating Nrf2 to scavenge ROS, inhibiting NF-kappa B phosphorylation, and alleviating osteoporosis in ovariectomized (OVX) mice. Taken together, 4 -MC reduces ROS by inhibiting Keap1, thereby preventing OVX-induced bone loss.
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