title: Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.
abstract: BACKGROUND
  Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models.
  
  
  METHODS
  Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model.
  
  
  RESULTS
  Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase.
  
  
  CONCLUSIONS
  Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease.
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Republic of Korea; Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of 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, Republic of Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Kyung Kim
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hyen
authors.initials: H
authors.lastname: Joo Park
authors.affiliation: College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Lan
authors.initials: L
authors.lastname: Cho
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of 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, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of 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, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Ho Lee
authors.affiliation: Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Republic of 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, Republic of Korea. Electronic address: sklee61@snu.ac.kr.
authors.forename: Sang
authors.initials: S
authors.lastname: Kook Lee
mesh_terms: D016475:3T3 Cells; D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001846:Bone Development / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000187:drug effects; D001862:Bone Resorption / Q000517:prevention & control; D002478:Cells, Cultured; D005260:Female; D057889:Iridoid Glycosides / Q000627:therapeutic use*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D011714:Pyrans / Q000627:therapeutic use*; D053245:RANK Ligand / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; D057889:Iridoid Glycosides; D011714:Pyrans; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D015675:Osteocalcin; C033250:harpagide
keywords: Anti-osteoporotic activity; H. procumbens var. sublobatum (Engl.) Stapf; Harpagide; Osteoblast; Osteoclast; Ovariectomized mice