2. Academic Validation
  3. Safflower yellow promotes angiogenesis through p-VHL/ HIF-1α/VEGF signaling pathway in the process of osteogenic differentiation

Safflower yellow promotes angiogenesis through p-VHL/ HIF-1α/VEGF signaling pathway in the process of osteogenic differentiation

  • Biomed Pharmacother. 2018 Nov;107:1736-1743. doi: 10.1016/j.biopha.2018.06.119.
Zhi Tang 1,  Hongzan Xie 1,  Shengping Jiang 1,  Shen Cao 1,  Yunqing Pu 1,  Biao Zhou 2,  Xuqiao Zhang 1,  Hui Xiong 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, Traditional Chinese Medicine of Xiangtan City, Xiangtan, 411100, PR China.
  • 2 Department of Orthopedics, Hunan University of Traditional Chinese Medicine, Changsha, 410208, PR China.
  • 3 Department of Orthopedics, Hunan University of Traditional Chinese Medicine, Changsha, 410208, PR China. Electronic address: xionghui20180125@sina.com.
PMID: 30257392 DOI: 10.1016/j.biopha.2018.06.119
Abstract

Objective: Safflower yellow (SY) is an active component ofCarthamus tinctorius L. that is widely used in orthopedics. This study aimed to evaluate the role of SY in angiogenesis and osteogenic differentiation.

Methods: The migration and in vitro angiogenesis of SY (4.5, 9.0, 18 μg/ml)-treated human umbilical vein endothelial cells (HUVEC-12) were assessed by transwell and tube formation assay, respectively. Osteogenic differentiation ability was detected by Alkaline Phosphatase (ALP) and Alizarin Red S staining. The mRNA and protein expressions of related markers were determined by RT-qPCR and Western blot.

Results: The migration and tube formation ability of HUVEC-12 were promoted by SY. Furthermore, SY facilitated the angiogenesis and osteogenic differentiation in the co-culture of HUVEC-12 and BMSCs by increasing hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), Angiopoietin-2 (ANG-2), ALP, runt-related transcription factor 2 (Runx2) and osteopontin-1 (OPN-1) levels. Inhibition of HIF-1α expression by 3-(5-hydroxymethl-2-furyl)-1-benzylindazole (YC-1), restrained SY-induced proliferation, migration and angiogenesis of HUVEC-12 and the increased protein levels of VEGF, ANG-2, ALP, Runx2 and OPN-1. Finally, WD repeat and SOCS box-containing protein-1 (WSB-1)/Von Hippel-Lindau protein (p-VHL) pathway was involved in the beneficial effect of SY.

Conclusion: SY promotes osteogenic differentiation via enhancing angiogenesis by regulating pVHL/HIF-1α/VEGF signaling pathway.

Keywords

Angiogenesis; Osteogenic differentiation; Safflower yellow; p-VHL/ HIF-1α/ VEGF signaling pathway.

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