Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts

作者：Chung Hwa Jin; Kim Won Kyung; Oh Jedo; Kim Me riong; Shin Joon Shik; Lee Jinho; Ha In Hyuk; Lee Sang Kook^*

来源：Journal of Natural Products, 2017, 80(2): 434-442.

DOI：10.1021/acs.jnatprod.6b00964

Harpagoside (1) is an iridoid glycoside isolated from the radix of Harpagophytum procumbens var. sublobatum, commonly called Devil's claw. The anti-osteoporotic effect of 1 was investigated in both in vitro cell cultures and in vivo using an ovariectomized (OVX) mouse model. Compound 1 induced bone formation by stimulating osteoblast proliferation, alkaline phosphatase activity, and mineralization in osteoblastic MC3T3-E1 cells. Treatment with 1 increased the mRNA and protein expression of bone formation biomarkers through regulation of the BMP2 and Wnt signaling pathway in MC3T3-E1 cells. Compound 1 also suppressed the RANKL-induced osteoclastogenesis of cultured mouse bone marrow cells. Oral administration of 1 restored the OVX-induced destruction of trabecular bone. The bone mineral density of the femur was also increased significantly by 1. The elevated serum levels of osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase in the OVX mice were decreased by treatment with 1. These findings suggest that compound 1 may protect against bone loss induced by OVX in mice by regulating stimulation of osteoblast differentiation and inhibition of osteoclast resorption. Therefore, harpagoside (1) is a potential candidate for management of postmenopausal osteoporosis.

• 出版日期2017-2