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Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats

  • Authors:
    • Wen‑Ji Shangguan
    • Yue‑Hui Zhang
    • Zhan‑Chun Li
    • Lu‑Min Tang
    • Jiang Shao
    • He Li
  • View Affiliations / Copyright

    Affiliations: Department of Traditional Chinese Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Orthopedic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
    Copyright: © Shangguan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1741-1749
    |
    Published online on: September 28, 2017
       https://doi.org/10.3892/ijmm.2017.3160
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Abstract

In this study, to investigate the effects of naringin on vascular endothelial cell (VEC) function, proliferation, apoptosis, and angiogenesis, rat VECs were cultured in vitro and randomly divided into four groups: control, serum‑starved, low‑concentration naringin treatment, and high‑concentration naringin treatment. MTT assay was used to detect cell proliferation while Hoechst 33258 staining and flow cytometry were used to detect apoptosis. Changes in the expression of apoptosis‑associated proteins [GRP78, CHOP, caspase‑12, and cytochrome c (Cyt.c)] were detected using western blotting. JC‑1 staining was employed to detect changes in mitochondrial membrane potential. Intracellular caspase‑3, ‑8, and ‑9 activity was determined by spectrophotometry. ELISA was used to detect endothelin (ET), and a Griess assay was used to detect changes in the expression of nitric oxide (NO) in culture medium. The study further divided an ovariectomized (OVX) rat model of osteoporosis randomly into four groups: OVX, sham‑operated, low‑concentration naringin treatment (100 mg/kg), and high‑concentration naringin treatment (200 mg/kg). After 3 months of treatment, changes in serum ET and NO expression, bone mineral density (BMD), and microvessel density of the distal femur (using CD34 labeling of VECs) were determined. At each concentration, naringin promoted VEC proliferation in a time‑ and dose‑dependent manner. Naringin also significantly reduced serum starvation‑induced apoptosis in endothelial cells, inhibited the expression of GRP78, CHOP, caspase‑12, and Cyt.c proteins, and reduced mitochondrial membrane potential as well as reduced the activities of caspase‑3 and ‑9. Furthermore, naringin suppressed ET in vitro and in vivo while enhancing NO synthesis. Distal femoral microvascular density assessment showed that the naringin treatment groups had a significantly higher number of microvessels than the OVX group, and that microvascular density was positively correlated with BMD. In summary, naringin inhibits apoptosis in VECs by blocking the endoplasmic reticulum (ER) stress‑ and mitochondrial‑mediated pathways. Naringin also regulates endothelial cell function and promotes angiogenesis to exert its anti‑osteoporotic effect.
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Copy and paste a formatted citation
Spandidos Publications style
Shangguan WJ, Zhang YH, Li ZC, Tang LM, Shao J and Li H: Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. Int J Mol Med 40: 1741-1749, 2017.
APA
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., & Li, H. (2017). Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. International Journal of Molecular Medicine, 40, 1741-1749. https://doi.org/10.3892/ijmm.2017.3160
MLA
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., Li, H."Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats". International Journal of Molecular Medicine 40.6 (2017): 1741-1749.
Chicago
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., Li, H."Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats". International Journal of Molecular Medicine 40, no. 6 (2017): 1741-1749. https://doi.org/10.3892/ijmm.2017.3160
Copy and paste a formatted citation
x
Spandidos Publications style
Shangguan WJ, Zhang YH, Li ZC, Tang LM, Shao J and Li H: Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. Int J Mol Med 40: 1741-1749, 2017.
APA
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., & Li, H. (2017). Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats. International Journal of Molecular Medicine, 40, 1741-1749. https://doi.org/10.3892/ijmm.2017.3160
MLA
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., Li, H."Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats". International Journal of Molecular Medicine 40.6 (2017): 1741-1749.
Chicago
Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J., Li, H."Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats". International Journal of Molecular Medicine 40, no. 6 (2017): 1741-1749. https://doi.org/10.3892/ijmm.2017.3160
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