title: Plectranthus amboinicus attenuates inflammatory bone erosion in mice with collagen-induced arthritis by downregulation of RANKL-induced NFATc1 expression.
abstract: OBJECTIVE
  Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis.
  
  
  METHODS
  We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA.
  
  
  RESULTS
  Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts.
  
  
  CONCLUSIONS
  We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.
authors: Rheumatology/Immunology/Allergy, Tri-Service General Hospital, National Defense Medical Center, 161 MinChuan E. Road, Sec. 6, Neihu 114, Taipei, Taiwan, Republic of China.
authors: Yu-Chieh
authors: YC
authors: Hsu
authors: Chia-Pi
authors: CP
authors: Cheng
authors: Deh-Ming
authors: DM
authors: Chang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002460:Cell Line; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010000:Osteitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D031346:Plectranthus / Q000737:chemistry*; D061251:Primary Cell Culture; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000502:physiology; D000097123:Rosmarinic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D050071:Bone Density Conservation Agents; D002934:Cinnamates; D053630:Depsides; D050778:NFATC Transcription Factors; D010936:Plant Extracts; D053245:RANK Ligand; D000097123:Rosmarinic Acid; C494005:Nfatc1 protein, mouse; C505689:Tnfsf11 protein, mouse