title: Lactobacillus fermentation enhances the inhibitory effect of Hwangryun-haedok-tang in an ovariectomy-induced bone loss.
abstract: BACKGROUND
  Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model.
  
  
  METHODS
  Tartrate resistant acid phosphatase (TRAP) staining was employed to evaluate osteoclast formation. mRNA level of transcription factor and protein levels of signaling molecules were determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. Effect of HRT or fHRT on OVX-induced bone loss was evaluated using OVX rats orally administered HRT, or fHRT with 300 mg/kg for 12 weeks. Micro-CT analysis of femora was performed to analyze bone parameter.
  
  
  RESULTS
  HRT or fHRT treatment significantly decreased TRAP activity and the number of TRAP positive multinuclear cells on osteoclastogenesis. Interestingly, these inhibitory effects of HRT were enhanced by fermentation. Furthermore, fHRT significantly inhibited mRNA and protein expression of nuclear factor of activated T cells cytoplasmic 1, which leads to down-regulation of NFATc1-regulated mRNA expressions such as TRAP, the d2 isoform of vacuolar ATPase V(0) domain, and cathepsin K. Administration of fHRT significantly inhibited the decrease of bone mineral density, and improved bone parameter of femora more than that of HRT and vehicle in OVX rats.
  
  
  CONCLUSIONS
  This study demonstrated that lactic bacterial fermentation fortifies the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial potential on osteoporosis by inhibiting osteoclastogenesis.
authors.forename: Ki-Shuk
authors.initials: KS
authors.lastname: Shim
authors.forename: Taesoo
authors.initials: T
authors.lastname: Kim
authors.forename: Hyunil
authors.initials: H
authors.lastname: Ha
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Cho
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Seo
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000517:prevention & control; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005269:Femur; D005285:Fermentation; D006801:Humans; D007778:Lactobacillus / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy; D008517:Phytotherapy; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D050778:NFATC Transcription Factors; D053245:RANK Ligand