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. 2016 Jul;12(1):279-287.
doi: 10.3892/etm.2016.3333. Epub 2016 May 11.

Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway

Guangming Chen  1 , Chaopeng Wang  1 , Jiefang Wang  1 , Sujuan Yin  1 , Han Gao  1 , L U Xiang  1 , Hengrui Liu  1 , Yinquan Xiong  1 , Panpan Wang  2 , Xiaofeng Zhu  2 , L I Yang  1 , Ronghua Zhang  1
Affiliations

Antiosteoporotic effect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway (VSports)

V体育ios版 - Guangming Chen et al. Exp Ther Med. 2016 Jul.

Abstract

Icariin (ICA), the main active flavonoid glucoside isolated from Herba Epimedii, has been shown to prevent postmenopausal bone loss in vitro. However, the mechanisms by which ICA prevents bone loss in vivo remain poorly understood. In the present study, the effect of ICA in an ovariectomized (OVX) rat model of osteoporosis was evaluated. Sprague-Dawley rats were divided into sham-operated and OVX groups. The OVX rats were randomly divided into five groups: OVX group (water only), Fosamax (positive) group (5. 04 mg/kg, weekly, administered orally), and OVX-ICA groups (125, 250 or 500 mg/kg, daily, administered orally) and treated for 12 weeks. The 125, 250 and 500 mg/kg doses of ICA were designated as low (L-ICA), medium (M-ICA) and high (H-ICA), respectively. Compared with the sham-operated group, the OVX rats had significantly decreased bone mineral density (BMD), reduced serum osteoprotegerin (OPG) and increased serum bone gla protein (BGP) concentrations. ICA significantly increased BMD, biomechanical strength, trabecular bone number and trabecular bone thickness, and reduced lumbar trabecular bone separation. Treatment with ICA also completely normalized the expression of osteoblast markers by increasing serum concentrations of OPG and BGP. Enhanced mineralization was demonstrated by increased expression of differentiation markers. Although further in vivo studies are required to investigate the efficacy of ICA in improving bone mass, this study demonstrates that ICA has strong osteogenic activity, inducing osteogenic differentiation and inhibiting resorption by osteoclasts. It also demonstrates an antiosteoporotic effect for ICA on the basis of BMD, biochemical markers, biomechanical tests and histopathological parameters. Compared with L-ICA and H-ICA, M-ICA was more effective and caused no liver or kidney damage VSports手机版. .

Keywords: Herba Epimedii; icariin; in vivo; mechanism; osteoporosis V体育安卓版. .

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"V体育2025版" Figures

Figure 1.
Figure 1.
Three-point bending and compression tests to assess bone strength of the femur and vertebra. **P<0.01 vs. sham-operated; ▲P<0.05, ▲▲P<0.01 vs. OVX. OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day).
Figure 2.
Figure 2.
OPG levels in the six groups. As compared with the sham-operated group, expression of OPG was decreased in the OVX group and OPG levels were significantly increased in the positive and M-ICA groups. *P<0.05 vs. sham-operated; ▲P<0.05 vs. OVX. OPG, osteoprotegerin; OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day).
Figure 3.
Figure 3.
BGP levels in the six groups. Compared with the sham-operated group, BGP levels in the OVX group increased significantly (P<0.05). Compared with OVX group, levels of BGP in the positive group (P<0.01), and the L-ICA, M-ICA and H-ICA groups were significantly reduced (P<0.05). *P<0.05 vs. sham-operated; ▲P<0.05 and ▲▲P<0.01 vs. OVX. BGP, bone Gla protein; OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day).
Figure 4.
Figure 4.
Morphometric analysis. (A) Tb.N and Tb.Th decreased significantly in the OVX group compared with the sham group (P<0.01). Compared with the OVX group, the M-ICA group had significantly increased Tb.N and Tb.Th (P<0.05), while Tb.Sp decreased significantly (P<0.05), whereas in the L-ICA group, Tb.Th increased significantly and Tb.Sp decreased significantly (P<0.05). *P<0.05, **P<0.01 vs. sham-operated; ▲P<0.05 vs. OVX. (B) Micro-computed tomography analysis for the (a) sham, (b) OVX, (c) positive, (d) L-ICA, (e) M-ICA and (f) H-ICA groups. In comparison with the sham group, the bone trabecula is loose, fractured and exhibits loss in the OVX group. Following oral administration of ICA, the number of bone trabecula was clearly increased and the bone trabecula was more densely concatenated than that in the OVX group. Tb.N, trabecular number; Tb.Th, trabecular thickness; Tb.Sp, trabecular separation; OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day).
Figure 5.
Figure 5.
Histopathology of femurs from the six groups. (A) Sham, (B) OVX (C) positive, (D) L-ICA, (E) M-ICA and (F) H-ICA groups. Hematoxylin and eosin staining (magnification, ×40). OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day)..ask for letters to be removed.
Figure 6.
Figure 6.
mRNA expression levels determined by reverse transcription-quantitative polymerase chain reaction. Expression levels of (A) Lrp6, (B) GSK-3β, (C) β-catenin and (D) Runx2 mRNA. *P<0.05 vs. sham; ▲P<0.05 vs. OVX. Lrp6, low-density lipoprotein receptor-related protein 6; GSK-3β, glycogen synthase kinase-3β; Runx2, runt-related transcription factor 2; OVX, ovariectomy; ICA, icariin; Sham, sham-operated; Positive, treated with alendronate sodium; L-ICA, low dose ICA (125 mg/kg/day); M-ICA, medium dose ICA (250 mg/kg/day); H-ICA, high dose ICA (500 mg/kg/day).
Figure 7.
Figure 7.
Western blotting results for β-catenin. *P<0.05 vs. sham; ▲P<0.05 vs. OVX. GAPDH, glyceraldehyde 3-phosphate; OVX, ovariectomy; M-ICA, medium dose icariin (250 mg/kg/day).
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