title: Anti-Osteoporotic Activity of Harpagoside by Upregulation of the BMP2 and Wnt Signaling Pathways in Osteoblasts and Suppression of Differentiation in Osteoclasts.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University , Seoul 151-742, Korea.
authors.forename: Won Kyung
authors.initials: WK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University , Seoul 151-742, Korea.
authors.forename: Jedo
authors.initials: J
authors.lastname: Oh
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation , Seoul 135-896, Korea.
authors.forename: Me-Riong
authors.initials: MR
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation , Seoul 135-896, Korea.
authors.forename: Joon-Shik
authors.initials: JS
authors.lastname: Shin
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation , Seoul 135-896, Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation , Seoul 135-896, Korea.
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University , Seoul 151-742, Korea.
authors.forename: Sang Kook
authors.identifier: 0000-0002-4306-7024
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005269:Femur / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D031684:Harpagophytum / Q000737:chemistry*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000032:analysis / Q000097:blood; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism / Q000494:pharmacology; D056910:Republic of Korea; D015533:Transcriptional Activation; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D006027:Glycosides; D011714:Pyrans; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D015675:Osteocalcin; C033249:harpagoside