title: Effect of the combinatory mixture of Rubus coreanus Miquel and Astragalus membranaceus Bunge extracts on ovariectomy-induced osteoporosis in mice and anti-RANK signaling effect.
abstract: BACKGROUND
  Postmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus and Astragalus membranaceus have been used for their various pharmacological properties in Asia as a traditional medicine. The present study evaluated the anti-osteoporotic effects of the optimal combination of Rubus coreanus and Astragalus membranaceus in 7:3 mixture (RAM) in ovariectomized (OVX) mice by investigating bone biomechanical properties and the serum levels of TNF-α, osteocalcin, RANKL, OPG, and RANK-RANKL signal-related osteoclast differentiation markers.
  
  
  METHODS
  A total of 36 mature female outbred ICR (Institute of cancer research) strain mice (7 weeks) were divided into 6 groups with 7 mice in each group as follows: (1) Sham-operated control mice (Sham) received daily oral phosphate-buffered-saline (PBS) of equal volumes through gavage. (2) OVX mice received a daily oral gavage of PBS (OVX). (3) OVX mice were treated daily with 50mg/kgb.w./day of RAM (4) with 100mg/kgb.w./day of RAM or (5) with 200mg/kgb.w./day of RAM via oral gavage. (6) OVX mice received i.p. injections of 17β-estradiol (E2) (0.1mg/kgb.w./day) three times per week for 12 weeks.
  
  
  RESULTS
  Micro-CT images showed that oral administration of RAM to OVX mice prevented tibial bone loss, preserved trabecular bone microarchitecture, and improved bone biomechanical properties. RAM administration also showed recovery effects on the levels of TNF-α, OPG and RANKL concentration in OVX-states. Additionally, we found that the mechanism by which RAM elicited anti-osteoporotic effects was by down-regulating the expression of TRAF6 and NFATc1 in RANKL-RANK pathway, a route of osteoclast differentiation, followed by reducing the production of osteoclast differentiation factors, calcitonin receptors and cathepsin K.
  
  
  CONCLUSIONS
  Our research strongly suggests that RAM can be clinically used in the prevention and treatment of postmenopausal osteoporosis.
authors: Department of Life Science, Gachon University, Seongnam 461-701, Republic of Korea.
authors: Hyun
authors: H
authors: Jung Koo
authors: Department of Herbal Medicine Resources, Kangwon National University, Samcheok 245-710, Republic of Korea.
authors: Eun-Hwa
authors: EH
authors: Sohn
authors: Department of Herbal Medicine Resources, Kangwon National University, Samcheok 245-710, Republic of Korea.
authors: Ye-Jin
authors: YJ
authors: Kim
authors: Department of Life Science, Gachon University, Seongnam 461-701, Republic of Korea.
authors: Seon-A
authors: SA
authors: Jang
authors: Department of Physical Therapy, Kangwon National University, Samcheok 245-710, Republic of Korea.
authors: Seung
authors: S
authors: Namkoong
authors: Department of Life Science, Gachon University, Seongnam 461-701, Republic of Korea. Electronic address: sckang73@gachon.ac.kr.
authors: Se
authors: S
authors: Chan Kang
mesh_terms: D000818:Animals; D027885:Astragalus propinquus; D056657:Cathepsin K / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005638:Fruit; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism* / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000097:blood; D010052:Ovariectomy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D018517:Plant Roots; D053245:RANK Ligand / Q000097:blood; D011859:Radiography; D018003:Receptors, Calcitonin / Q000235:genetics; D027824:Rosaceae; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053244:Osteoprotegerin; D010936:Plant Extracts; D053245:RANK Ligand; D018003:Receptors, Calcitonin; D048029:TNF Receptor-Associated Factor 6; C506031:Tnfrsf11b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: Astragalus membranaceus; OPG; Osteoporosis; Ovariectomy; RANKL; Rubus coreanus