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  • Title: Vinpocetine inhibits RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss.
    Author: Zhu M, Liu H, Sun K, Liu J, Mou Y, Qi D, Zhou C, Abudunaibi M, Tasiken B, Li J, Cheng H, Huang H.
    Journal: Biomed Pharmacother; 2020 Mar; 123():109769. PubMed ID: 31846839.
    Abstract:
    Osteoporosis is a result of impaired bone formation and/or excessive bone resorption. Osteoclasts are the only cells in the body that have a bone resorption function. Inhibiting osteoclast activity and differentiation is a way to treat osteoporosis. The current pharmacological treatment for osteoporosis has many shortcomings, and more effective treatments are needed. Vinpocetine (Vinp), a derivative of the alkaloid vincamine, has been used to treat cerebrovascular disorders and cognitive impairment for a long time. Vinp inhibits mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB)-dependent inflammatory responses and oxidative damage in which osteoclasts are often involved. However, the effects of Vinp on the regulation of osteoclast activity remain unknown. In this study, we found that Vinp significantly inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast and F-actin formation and decreased osteoclastic bone resorption in vitro. Vinp also suppressed the expression of osteoclast-specific genes, including NFATc1, c-Fos, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), and cathepsin K (CTSK) at both the mRNA and protein levels. Vinp reduced activation of NF-κB, MAPK, and AKT signaling during osteoclastogenesis and prevented the production of reactive oxygen species with increased nuclear factor erythroid 2-related factor 2, heme oxygenase 1, and NAD(P)H:quinone acceptor oxidoreductase 1 expression. Animal experiments consistently demonstrated that Vinp treatment significantly attenuated ovariectomy-induced bone loss with a decrease in the osteoclast number and decreases in serum levels of RANKL, TRAP, interleukin-1β, and tumor necrosis factor-alpha, as well as increased serum levels of osteoprotegerin. Taken together, our findings reveal that Vinp may be a potential pharmacological choice for preventing and treating osteoporosis.
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