title: Naringin improves bone properties in ovariectomized mice and exerts oestrogen-like activities in rat osteoblast-like (UMR-106) cells.
abstract: OBJECTIVE
  Naringin, a flavanone glycoside in citrus fruits, has been recently reported to stimulate bone formation in vitro and in vivo. The present study was designed to determine if naringin could exert oestrogen-like protective actions in bone.
  
  
  METHODS
  Young C57/BL6J mice were ovariectomized (OVX) and treated orally with naringin (0.2 or 0.4 mg*g(-1)*day(-1)), 17beta-oestradiol (2 microg*g(-1)*day(-1)) or its vehicle for 6 weeks. Bone mineral densities (BMD) and polar stresss-train index (SSI) were measured by peripheral quantitative computed tomography. Rat osteoblast-like UMR-106 cells were co-incubated with the oestrogen receptor (ER) antagonist ICI 182780 to determine if the effects of naringin on osteoblastic functions were ER dependent. Functional transactivation of ERalpha and ERbeta as well as ERalpha phosphorylation by naringin were also studied.
  
  
  RESULTS
  Naringin at 0.4 mg*g(-1)*day(-1) increased BMD at trabecular-rich bone in OVX mice. Naringin (at both doses) significantly increased SSI at distal femur and lumbar spine and increased biomechanical strength (ultimate load and energy for breaking) at tibia diaphysis in OVX mice. The stimulatory effects of naringin on osteoblastic functions could be abolished by co-incubation with ICI 182780 in UMR-106 cells. Naringin failed to stimulate ERalpha- or ERbeta-mediated oestrogen response element-dependent luciferase activity but could significantly induce ERalpha phosphorylation at serine 118, in UMR-106 cells.
  
  
  CONCLUSIONS
  Naringin was effective in protecting against OVX-induced bone loss in mice and its actions might be mediated through ligand-independent activation of ER in osteoblastic cells.
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, China.
authors.forename: Wai-Yin
authors.initials: WY
authors.lastname: Pang
authors.forename: Xin-Lun
authors.initials: XL
authors.lastname: Wang
authors.forename: Sau-Keng
authors.initials: SK
authors.lastname: Mok
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Lai
authors.forename: Hung-Kay
authors.initials: HK
authors.lastname: Chow
authors.forename: Ping-Chung
authors.initials: PC
authors.lastname: Leung
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density; D002460:Cell Line; D017931:DNA Primers; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D014599:Uterus / Q000187:drug effects
chemical_list: D017931:DNA Primers; D004965:Estrogen Antagonists; D004967:Estrogens; D044950:Flavanones; C005274:naringin
references.citation: Methods Mol Med. 2003;80:323-41
references.pmid: 12728728
references.citation: Mol Cell Biol. 2007 Feb;27(4):1516-30
references.pmid: 17158928
references.citation: Eur J Pharmacol. 2008 Jul 7;588(2-3):333-41
references.pmid: 18495116
references.citation: J Agric Food Chem. 2008 Aug 13;56(15):6185-205
references.pmid: 18593176
references.citation: Plant Foods Hum Nutr. 2006 Jun;61(2):57-65
references.pmid: 16816988
references.citation: Annu Rev Plant Biol. 2004;55:225-61
references.pmid: 15377220
references.citation: Nutrition. 2008 Oct;24(10):1039-44
references.pmid: 18595661
references.citation: Br J Pharmacol. 2009 Nov;158 Suppl 1:S1-254
references.pmid: 19883461
references.citation: Endocrinology. 1998 Oct;139(10):4252-63
references.pmid: 9751507
references.citation: Br J Nutr. 2006 Jun;95(6):1039-47
references.pmid: 16768824
references.citation: J Nutr. 2009 Dec;139(12):2230-6
references.pmid: 19793844
references.citation: Clin Lab. 2003;49(5-6):203-7
references.pmid: 15285175
references.citation: Science. 1995 Dec 1;270(5241):1491-4
references.pmid: 7491495
references.citation: J Nutr. 2001 Feb;131(2):235-41
references.pmid: 11160539
references.citation: Mol Endocrinol. 1994 Jan;8(1):21-30
references.pmid: 8152428
references.citation: Br J Cancer. 2004 Mar;90 Suppl 1:S2-6
references.pmid: 15094757
references.citation: Mol Endocrinol. 2005 Apr;19(4):833-42
references.pmid: 15695368
references.citation: Nutrition. 2006 May;22(5):559-63
references.pmid: 16472977
references.citation: Cell. 1989 Nov 3;59(3):477-87
references.pmid: 2805068
references.citation: J Med Food. 2006 Winter;9(4):582-6
references.pmid: 17201649
references.citation: Nutr Cancer. 1996;26(2):167-81
references.pmid: 8875554
references.citation: Eur J Clin Nutr. 2007 Apr;61(4):472-7
references.pmid: 17047689
references.citation: J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):64-71
references.pmid: 17936617
references.citation: EMBO J. 1996 May 1;15(9):2174-83
references.pmid: 8641283
references.citation: J Med Food. 2008 Mar;11(1):99-104
references.pmid: 18361744
references.citation: Nucleic Acids Res. 1989 Jul 25;17(14):5477-88
references.pmid: 2762146
references.citation: Am J Chin Med. 2007;35(4):663-7
references.pmid: 17708632
references.citation: Clin Orthop Relat Res. 1996 Feb;(323):65-74
references.pmid: 8625608
references.citation: Phytomedicine. 2009 Jun;16(6-7):513-20
references.pmid: 18930642
references.citation: Evid Based Complement Alternat Med. 2005 Sep;2(3):353-61
references.pmid: 16136213
references.citation: Oncogene. 2002 Jul 25;21(32):4921-31
references.pmid: 12118371
references.citation: J Nutr. 2003 Jun;133(6):1892-7
references.pmid: 12771335
references.citation: Science. 2002 Oct 25;298(5594):843-6
references.pmid: 12399595
references.citation: Bone. 2003 Feb;32(2):136-41
references.pmid: 12633785
references.citation: Br J Nutr. 2008 Mar;99(3):494-502
references.pmid: 17764596
references.citation: J Agric Food Chem. 2000 Jan;48(1):56-9
references.pmid: 10637051
references.citation: Toxicology. 2001 Sep 14;166(1-2):79-89
references.pmid: 11518614
references.citation: Steroids. 2003 Jan;68(1):1-9
references.pmid: 12475718
references.citation: Am J Med. 2006 Apr;119(4 Suppl 1):S3-S11
references.pmid: 16563939
references.citation: J Orthop Res. 2006 Nov;24(11):2045-50
references.pmid: 16944474