RT-qPCR showed HYP significantly upregulates SRC, PI3K, AKT1, and e-NOS, activating the estrogen-PI3K/VEGF pathway.<h4>Conclusion</h4>HYP plays an anti-oxidative stress effect through targeted regulation of estrogen-PI3K/VEGF signal axis, and then promotes osteoblast differentiation and bone formation, which provides a new potential candidate drug and experimental basis for the treatment of osteoporosis. Here, VEGFA is linked to osteoporosis.