title: High-dose diosgenin reduces bone loss in ovariectomized rats via attenuation of the RANKL/OPG ratio.
abstract: The aim of this study was to evaluate effect of diosgenin (DG) on rats that had osteoporosis-like features induced by ovariectomy (OVX). Seventy-two six-month-old female Wistar rats were subjected to either ovariectomy (n = 60) or Sham operation (SHAM group, n = 12). Beginning at one week post-ovariectomy, the OVX rats were treated with vehicle (OVX group, n = 12), estradiol valerate (EV group, n = 12), or DG at three doses (DG-L, -M, -H group, n = 12, respectively). After a 12-week treatment, administration of EV or DG-H inhibited OVX-induced weight gain, and administration of EV or DG-H or DG-M had a significantly uterotrophic effect. Bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated by immunohistochemistry and in situ hybridization. Our results show that DG at a high dose (DG-H) had a significant anti-osteoporotic effect compared to OVX control. DG-H treatment down-regulated expression of RANKL and up-regulated expression of OPG significantly in tibia from OVX rats compared to control, and thus lowered the RANKL/OPG ratio. This suggests that the anti-osteoporotic effect of DG might be associated with modulating the RANKL/OPG ratio and DG had potential to be developed as alternative therapeutic agents of osteoporosis induced by postmenopause.
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. zzgtcm@163.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. sdsg_sch_86@126.com.
authors.forename: Changheng
authors.initials: C
authors.lastname: Song
authors.affiliation: Clinical Medical College of Chinese and Western Medicine, Shaanxi University of Chinese Medicine, Xi'an 712046, China. xiaoweifu@163.com.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Fu
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. meimei64571@sina.com.
authors.forename: Meijie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. lei_ruo@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. jh-p@163.com.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Pan
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. liuhong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. wangshaojun@163.com.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. xlh891201@sina.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE 68131, USA. gxiao@creighton.edu.
authors.forename: Gary Guishan
authors.initials: GG
authors.lastname: Xiao
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China. judahong@sohu.com.
authors.forename: Dahong
authors.initials: D
authors.lastname: Ju
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004144:Diosgenin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D010052:Ovariectomy / Q000009:adverse effects; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D004958:Estradiol; D004144:Diosgenin