Comparative study of holothurin A and echinoside A on inhibiting the high bone turnover via downregulating PI3K/AKT/β-catenin and OPG/RANKL/NF-κB signaling in ovariectomized mice

stimulating CB1 and MKP-1, downregulating the PI3K/AKT/β-catenin signal pathway. The OPG/RANKL/NF-κB pathway was identified as a critical regulator of bone resorption. Further investigation revealed that HA and EA significantly downregulate the expression of IKK, NF-κB and phosphorylated NF-κB p65, suppressing the expression of osteoclastogenesis transcription factors c-fos and NFATC1. To the best of our knowledge, this is the first report showing that both HA and EA improved osteoporosis, and these activities depend on the structure of saponins. These findings would provide guidance for the application of saponins in the management of osteoporosis.