Background: Forkhead box O1 (FoxO1)/β-catenin signaling pathway is a main oxidative defense pathway, which plays essential roles in the regulation of osteoporosis (OP). The natural products possess quality therapeutic effects and few side effects. It is used as a novel strategy in the treatment of OP. However, there is no systematic study in the natural antioxidant drug based on the FoxO1/β-catenin signaling pathway. This paper aims to discover pro-osteogenesis natural antioxidants for the prevention and treatment of OP.
Methods: Systems pharmacology; combined with reverse drug targeting, systems-ADME process, network analysis and molecular docking, was used to screen natural antioxidants based on the FoxO1/β-catenin signaling pathway. Then in vitro experiments were performed to evaluate the osteogenesis effects of screened natural antioxidants.
Results: Kaempferide was screened as the most potential antioxidant to improve osteogenesis by the regulation of the FoxO1/β-catenin signaling pathway. In vitro experiments showed that kaempferide significantly increased the expression of antioxidant genes and promoted osteogenic differentiation. Furthermore, kaempferide also improved the osteogenic differentiation inhibited by H2O2 through the enhancement of antioxidant capacity. Notably, kaempferide promoted cell antioxidant capacity by the increased nuclear translocation of FoxO1 and β-catenin.
Conclusions: These findings suggest that kaempferide is the natural antioxidant to promote osteogenesis effectively through the FoxO1/β-catenin signaling pathway. Natural antioxidant therapy maybe a promising strategy for the prevention and treatment of OP.
Keywords: Antioxidant; FoxO1/β-catenin signaling pathway; Kaempferide; Osteogenesis; Systems pharmacology.
Copyright © 2021. Published by Elsevier B.V.