5,7-Dihydroxycoumarin counteracts osteoporosis by inhibition of PI3K/Akt signaling to suppress osteoclastogenesis: A study-based network pharmacology and experimental validation - PubMed
a day ago
- #osteoporosis
- #osteoclastogenesis
- #PI3K/Akt signaling
- 5,7-Dihydroxycoumarin (5,7-DHC) is investigated for its potential to counteract osteoporosis by suppressing osteoclastogenesis through inhibition of the PI3K/Akt signaling pathway.
- Network pharmacology identified 47 overlapping genes between 5,7-DHC targets and osteoporosis-related genes, enriched in pathways such as PI3K/Akt, MAPK, and EGFR.
- Molecular docking and dynamics simulations showed strong binding affinity between 5,7-DHC and Akt1, supporting its interaction with key signaling molecules.
- In vitro studies demonstrated that 5,7-DHC inhibits osteoclast differentiation, reduces F-actin ring formation, decreases acidified vesicle secretion and bone resorption, and downregulates osteoclast-related markers like NFATc1 and CTSK.
- Mechanistically, 5,7-DHC suppresses phosphorylation of PI3K, Akt, and GSK3β during early osteoclastogenesis, highlighting its role in modulating signaling pathways.
- In vivo experiments on ovariectomized mice showed that 5,7-DHC attenuates bone loss, improves trabecular microarchitecture (e.g., increased BV/TV and BMD), and enhances histological morphology.