title: Panax notoginseng saponins mitigate ovariectomy-induced bone loss and inhibit marrow adiposity in rats.
abstract: OBJECTIVE
  Previous data have suggested that Panax notoginseng saponins (PNS) can prevent estrogen deficiency-induced bone loss by dual action: stimulation of new bone formation and inhibition of bone resorption. Marrow adipogenesis has been identified as a negative indicator of skeletal strength and integrity. This study assessed the effects of early PNS supplementation on bone microarchitecture preservation and marrow fat content in an ovariectomized rat model.
  
  
  METHODS
  Forty adult female Sprague-Dawley rats were randomly assigned to four equal groups for 12 weeks of treatment: (1) sham operation (SHAM) + vehicle; (2) ovariectomy (OVX) + vehicle; (3) OVX + 17β-estradiol (25 μg/kg); (4) OVX + PNS (300 mg/kg/d, PO). Marrow fat content of the femur was determined, using fat/water magnetic resonance imaging (MRI), at baseline and 6 and 12 weeks after operation. At the end of the experiment, bone turnover, trabecular microarchitecture, and marrow adipocytes were assessed by serum biomarkers, micro-computed tomography (micro-CT), and histopathology, respectively. The effects of PNS on adipocytic differentiation were reflected by expression levels of the adipogenic genes PPARγ2 and C/EBPα, as determined by reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Ovariectomized rats experienced remarkable increases in marrow fat content across time points, which were accompanied by elevated rate of bone turnover, global volumetric bone density, and trabecular microarchitecture deterioration. These OVX-induced pathological changes are reversible in that most of them could be mostly corrected upon 17β-estradiol treatment. PNS treatment significantly reduced marrow adipogenesis (adipocyte density, -27.2%; size, -22.7%; adipocyte volume-to-tissue volume ratio, -53.3%; all P < 0.01) and adipocyte marker gene expression, and prevented bone mass loss and microarchitecture deterioration. Moreover, PNS enhanced osteoblast activity but suppressed osteoclast turnover, as evidenced by decreased levels of serum C-terminal telopeptides of type I collagen and elevated levels of alkaline phosphatase.
  
  
  CONCLUSIONS
  PNS mitigates estrogen deficiency-induced deterioration of trabecular microarchitecture and suppresses marrow adipogenesis.
authors.affiliation: 1Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China 2Department of Gastroenterology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 3Department of Radiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 4Department of Pharmacy, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jing-Zheng
authors.initials: JZ
authors.lastname: Fan
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Guan-Wu
authors.initials: GW
authors.lastname: Li
authors.forename: Shi-Xin
authors.initials: SX
authors.lastname: Chang
authors.forename: Hua
authors.initials: H
authors.lastname: Nian
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Liang
mesh_terms: D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology*; D001842:Bone and Bones / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy; D053723:Panax notoginseng / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000627:therapeutic use*; D014599:Uterus / Q000187:drug effects
chemical_list: D012503:Saponins; D004958:Estradiol