title: Eurycoma longifolia upregulates osteoprotegerin gene expression in androgen- deficient osteoporosis rat model.
abstract: BACKGROUND
  Eurycoma longifolia (EL) has been shown recently to protect against bone calcium loss in orchidectomised rats, the model for androgen-deficient osteoporosis. The mechanism behind this is unclear but it may be related to its ability to elevate testosterone levels or it may directly affect bone remodeling. The aim of this study is to determine the mechanism involved by investigating the effects of EL extract on serum testosterone levels, bone biomarkers, biomechanical strength and gene expression of Receptor Activator of Nuclear Factor kappa-B ligand (RANKL), Osteoprotegerin (OPG) and Macrophage-Colony Stimulating Factor (MCSF) in orchidectomised rats.
  
  
  METHODS
  Thirty-two male Sprague-Dawley rats were divided into: Sham-operated group (SHAM); orchidectomised-control group (ORX); orchidectomised and given 15 mg/kg EL extract (ORX + EL) and orchidectomised and given 8 mg/kg testosterone (ORX + T). The rats were treated for 6 weeks. The serum levels of testosterone, osteocalcin and C-terminal telopeptide of type I collagen (CTX) were measured using the ELISA technique. The femoral bones were subjected to biomechanical testing. The tibial bone gene expressions of RANKL, OPG and MCSF were measured using the branch DNA technique.
  
  
  RESULTS
  The post-treatment level of testosterone was found to be significantly reduced by orchiectomy (p < 0.05). Both ORX + EL and ORX + T groups have significantly higher post-treatment testosterone levels compared to their pre-treatment levels (p < 0.05). The bone resorption marker (CTx) was elevated after orchiectomy but was suppressed after treatment in the ORX + EL and ORX + T groups (p < 0.05). There was no significant finding for the femoral biomechanical parameters. The tibial OPG gene expression in the ORX group was significantly lower compared to the SHAM and ORX + EL groups (p < 0.05).
  
  
  CONCLUSIONS
  Supplementation with EL extract elevated the testosterone levels, reduced the bone resorption marker and upregulated OPG gene expression of the orchidectomised rats. These actions may be responsible for the protective effects of EL extract against bone resorption due to androgen deficiency.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National University of Malaysia, Jalan Raja Muda Abd Aziz, KL, Malaysia. anazrun@yahoo.com
authors.forename: Ahmad Nazrun
authors.initials: AN
authors.lastname: Shuid
authors.forename: Eman
authors.initials: E
authors.lastname: El-arabi
authors.forename: Nadia Mohd
authors.initials: NM
authors.lastname: Effendy
authors.forename: Halimaton Saadiah Abdul
authors.initials: HS
authors.lastname: Razak
authors.forename: Norliza
authors.initials: N
authors.lastname: Muhammad
authors.forename: Norazlina
authors.initials: N
authors.lastname: Mohamed
authors.forename: Ima Nirwana
authors.initials: IN
authors.lastname: Soelaiman
mesh_terms: D000728:Androgens / Q000172:deficiency*; D000818:Animals; D004195:Disease Models, Animal; D035701:Eurycoma / Q000737:chemistry*; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000728:Androgens; D053244:Osteoprotegerin; D010936:Plant Extracts; D053245:RANK Ligand; D013739:Testosterone