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

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    Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts
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    † College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Korea
    ‡ Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea
    *Tel: +82-2-880-2475. Fax: +82-2-762-8322. E-mail: [email protected]
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    Journal of Natural Products

    Cite this: J. Nat. Prod. 2017, 80, 2, 434–442
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.6b00964
    Published January 20, 2017
    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy
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    Abstract

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    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.

    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy

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    Journal of Natural Products

    Cite this: J. Nat. Prod. 2017, 80, 2, 434–442
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.6b00964
    Published January 20, 2017
    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy
    Request reuse permissions

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