Entry #: 25
Date: 25 November 2017
Section: Wound healing
Topic: Hydroxytyrosol and proliferation of endothelial cells
Type: Original Paper

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OliveNetTMJournal Club

Expert review of literature related to olives and olive oil

D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Hydroxytyrosol contributes to cell proliferation and inhibits apoptosis in pulsed electromagnetic fields treated human umbilical vein endothelial cells in vitro


Cheng et al

Citation / Year

(1) / 2017


Wound healing, hydroxytyrosol, human umbilical vein endothelial cells, pulsed electromagnetic fields, cellular proliferation


The beneficial effects of extra-virgin olive oil and various Olea-derived extracts on the skin are well known. In this study an in vitro model using human umbilical vein endothelial cells was utilised to examine the biological effects of a key olive polyphenol, hydroxytyrosol, together with pulsed electromagnetic fields. Pulsed electromagnetic field therapy, utilizes specialized equipment to create an energy field which has been shown to promote cellular proliferation, modulate gene expression and enhance the synthesis of extracellular matrix proteins (2). For example, using a pulsed electromagnetic field (20 Hz for 1 hour per day), has been shown to accelerate diabetic wound healing in rodents (3); extending the results of other studies (for example, (2)). At molecular level, pulsed field electromagnetic fields have been shown to increase the secretion of vascular endothelial growth factor, connective tissue growth factor and endothelial nitric oxide synthase in endothelial cells (4). Further, pulsed field electromagnetic fields have been shown to increase tube formation, migration, and proliferation and to attenuate hypoxia-induced apoptosis in human endothelial cells (5). In addition, hydroxytyrosol has been shown to inhibit matrix metalloproteinase-9 and cyclooxygenase-2 thereby reducing inflammatory processes in endothelial cells (6). Similarly, hydroxytyrosol has been found to stabilize nuclear factor erythroid 2-related factor 2 resulting in increased expression of the heme oxygenase-1 antioxidant enzymes in vascular endothelial cells (7). These effects of pulsed field electromagnetic fields and hydroxytyrosol in endothelial cells provide the basis of this study aimed at investigating the combinatorial effects in human umbilical vein endothelial cells.

Key points and implications

Using a series of conventional in vitro cell culture assays, it was shown that combinations of pulsed field electromagnetic field and hydroxytyrosol results in: 1) enhanced cellular proliferation using scratch migration assays, 2) reduced hydrogen peroxide-induced apoptosis, and 3) enhanced expression levels (mRNA and protein) of Akt, mTOR and Tgf-β, which represents a key pathway for accelerating epithelial wound healing (8). Although a relatively simple series of in vitro experiments in a single cell line were performed, the findings are promising and highlight that combinations of olive phenolics with conventional or experimental approaches may provide new avenues for potentially enhancing wound healing.

Related publications

  1. Y. Cheng, Z. Qu, X. Fu, Q. Jiang, J. Fei, Hydroxytyrosol contributes to cell proliferation and inhibits apoptosis in pulsed electromagnetic fields treated human umbilical vein endothelial cells in vitro. Molecular medicine reports 16, 8826-8832 (2017).
  2. A. Athanasiou et al., The effect of pulsed electromagnetic fields on secondary skin wound healing: an experimental study. Bioelectromagnetics 28, 362-368 (2007).
  3. I. Goudarzi, S. Hajizadeh, M. E. Salmani, K. Abrari, Pulsed electromagnetic fields accelerate wound healing in the skin of diabetic rats. Bioelectromagnetics 31, 318-323 (2010).
  4. C. F. Martino, H. Perea, U. Hopfner, V. L. Ferguson, E. Wintermantel, Effects of weak static magnetic fields on endothelial cells. Bioelectromagnetics 31, 296-301 (2010).
  5. R. L. Li et al., Pulsed electromagnetic field improves postnatal neovascularization in response to hindlimb ischemia. American journal of translational research 7, 430-444 (2015).
  6. E. Scoditti et al., Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. Archives of biochemistry and biophysics 527, 81-89 (2012).
  7. H. Zrelli, M. Kusunoki, H. Miyazaki, Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo Synthesis and Stabilization. Phytotherapy research : PTR 29, 1011-1018 (2015).
  8. R. M. Castilho, C. H. Squarize, J. S. Gutkind, Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing. Oral diseases 19, 551-558 (2013).