Crocetin promotes angiogenesis in human endothelial cells through PI3K-Akt-eNOS signaling pathway

Authors

  • Mahdieh Nasirzadeh Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Yousef Rasmi Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran; Tel: +98(44)32770698; Fax: +98(44)32780800; E-mail: rasmiy@umsu.ac.ir
  • Reza Rahbarghazi Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
  • Fatemeh Kheradmand Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Mojtaba Karimipour Department of Anatomy, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Pornanong Aramwit Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phaya Thai Road, Phatumwan, Bangkok 10330, Thailand
  • Maryam Astinfeshan Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Zafar Gholinejad Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Behrokh Daeihasani Department of Biology, Payame Noor University, P.O.Box 19395-3697, Tehran, Iran
  • Ehsan Saboory Neuroscience Research Center, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Alireza Shirpoor Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  • Aysa Rezabakhsh Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  • Elmira Zolali Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
  • Naser Khalaji Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

DOI:

https://doi.org/10.17179/excli2019-1175

Keywords:

crocetin, human endothelial cells, angiogenesis, tube formation, migration, VEGFR-2- Akt-eNOS signaling

Abstract

Previous studies proved the pro-angiogenic effect of Crocetin, a natural carotenoid dicarboxylic acid, in both in vivo and in vitro models. However, the exact mechanism of Crocetin action has not completely been elucidated yet. The current experiment was designed to find the activity of PI3K-Akt-eNOS axis after the treatment of endothelial cells with Crocetin in vitro. Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with various concentrations of Crocetin (1, 5, 25, 50, and 100 µM) over a period of 72 h. Crocetin significantly increased HUVECs viability after 72 h as compared with the control group. We also found that Crocetin promoted the formation of the capillary-like structure compared to the control (p<0.05). Moreover, an improved migration rate and increased MMP-9 activity were observed in HUVECs that received 50 µM Crocetin (p<0.05). Crocetin enhanced the uptake of Ac-LDL which is correlated with increased lipid metabolism. Based on the data from the current experiment, protein level of VEGFR-1, -2 and p-Akt/Akt, p-eNOS/eNOS ratios were increased 72 h after the treatment of HUVECs with Crocetin (p<0.05). In contrast, the transcription level of VEGF was reduced in Crocetin-treated cells. These data demonstrated that Crocetin promotes HUVECs angiogenesis potential by the modulation of VEGF signaling pathway and increased cell viability. The PI3K/Akt/eNOS axis is required for a Crocetin-associated activity in endothelial cells.

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Published

2019-10-21

How to Cite

Nasirzadeh, M., Rasmi, Y., Rahbarghazi, R., Kheradmand, F., Karimipour, M., Aramwit, P., … Khalaji, N. (2019). Crocetin promotes angiogenesis in human endothelial cells through PI3K-Akt-eNOS signaling pathway. EXCLI Journal, 18, 936–949. https://doi.org/10.17179/excli2019-1175

Issue

Vol. 18 (2019)

Section

Original articles

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