Research Paper Volume 13, Issue 13 pp 17370—17379
Baicalein ameliorates osteoporosis via AKT/FOXO1 signaling
- 1 Department of Orthopedics, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
- 2 Department of Laboratory Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, China
- 3 Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200941, China
Received: February 22, 2021 Accepted: May 18, 2021 Published: July 1, 2021https://doi.org/10.18632/aging.203227
How to Cite
Copyright: © 2021 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In this study, we used bioinformatics and an in vitro cellular model of glucocorticoid-induced osteoporosis to investigate mechanisms underlying the beneficial effects of baicalein (BN) against osteoporosis. STITCH database analysis revealed 30 BN-targeted genes, including AKT1, CCND1, MTOR, and PTEN. Functional enrichment analysis demonstrated that BN-targeted genes were enriched in 49 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. MIRWALK2.0 database analysis identified 110 enriched KEGG pathways related to osteoporosis. A Venn diagram demonstrated that 26 KEGG pathways were common between osteoporosis and BN-targeted genes. The top 5 common KEGG pathways were prostate cancer, bladder cancer, glioma, pathways in cancer, and melanoma. BN-targeted genes in the top 5 shared KEGG pathways were involved in PI3K-AKT, MAPK, p53, ErbB, and mTOR signaling pathways. In addition, glucocorticoid-induced osteoporosis in MC3T3-E1 cells was partially reversed by BN through inhibition of AKT, which, by upregulating FOXO1, enhanced expression of bone turnover markers (ALP, OCN, Runx2, and Col 1) and extracellular matrix mineralization. These findings demonstrate that BN suppresses osteoporosis via an AKT/FOXO1 signaling pathway.