7,8-DHF inhibits BMSC oxidative stress via the TRKB/PI3K/AKT/NRF2 pathway to improve symptoms of postmenopausal osteoporosis

Postmenopausal osteoporosis (PMO) is characterized by bone loss and microstructural damage, and it is most common in older adult women. Currently, there is no cure for PMO. The flavonoid chemical 7,8-dihydroxyflavone (7,8-DHF) specifically activates tropomyosin receptor kinase B (TRKB). Furthermore, 7,8-DHF has various biological characteristics, including anti-inflammatory and antioxidant effects. However, the specific implications and fundamental mechanisms of 7,8-DHF in PMO remain unclear. We used protein imprinting, flow cytometry, tissue staining, and other methods to estimate the preventive mechanisms of 7,8-DHF against hydrogen peroxide (H 2 O 2 )-induced apoptosis in primary mouse bone marrow mesenchymal stem cells (BMSCs), osteogenic differentiation ability, and bone mass in ovariectomized (OVX) mice. We found that 7,8-DHF effectively prevented H 2 O 2 -induced reductions in the viability and osteogenic differentiation capacity of primary BMSCs. Mechanistically, 7,8-DHF induced the TRKB to activate the PI3K/AKT/NRF2 pathway. In vivo experiments with the OVX mouse model confirmed that 7,8-DHF can inhibit oxidative stress and promote bone formation, indicating that 7,8-DHF improves the viability and osteogenic differentiation ability of BMSCs stimulated via H 2 O 2 by activating the TRKB/PI3K/AKT and NRF2 pathways, thereby improving PMO. • 7,8-DHF can inhibit H 2 O 2 -induced oxidative stress in BMSCs and restore the osteogenic differentiation ability of BMSCs. • 7,8-DHF enhances BMSCs antioxidant stress capacity by activating the TRKB/PI3K/AKT/NRF2 signaling pathway. • 7,8-DHF can reverse the downregulation of p-TRKB expression in BMSCs of postmenopausal osteoporotic mice. • 7,8-DHF improves oxidative stress markers in postmenopausal osteoporotic mice and treats postmenopausal osteoporosis.