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20 The polyphenol delphinidin induces antioxidant effects in human umbilical vein endothelial cells through activation of endogenous glutathione: importance of using relevant concentration in in vitro systems
  1. Katarzyna Goszcz1,
  2. Garry G Duthie2,
  3. Derek Stewart3,4,
  4. Ian L Megson1
  1. 1Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Centre for Health Science, Inverness, Scotland, UK
  2. 2Rowett Institute of Nutrition and Health, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK
  3. 3James Hutton Institute, Invergowrie, Dundee, Scotland, UK
  4. 4School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, UK

Abstract

Polyphenols are regarded to have a wide range of health-promoting effects. Increased consumption of polyphenol-rich food is known to be associated with numerous cardioprotective effects. Polyphenols have been shown to improve endothelial function, inhibit abnormal platelet aggregation, reduce inflammation and improve plasma lipid profiles. Moreover, polyphenols have been widely recognised as powerful antioxidants. Given that oxidative stress plays a key role in initiation and progression of atherosclerosis, antioxidant therapy with polyphenols has potential. However, the concentrations required to mediate sufficient antioxidant effect appear to be unattainable under in vivo conditions. Polyphenols are characterised by poor absorption, rapid degradation and extensive metabolism, culminating in poor bioavailability (~1 µM). In addition, they can also exhibit paradoxical pro-oxidant activities.

Spectrophotometric and mass spectrometry (LC-MS/MS) analysis of the phenolic compound, delphinidin, confirmed its low stability and rapid degradation (t1/2 ~30 min) under physiologically relevant conditions. Delphinidin degraded to smaller phenolics: gallic acid and phloroglucinol aldehyde. Moreover, both the parent compound and its main metabolite, gallic acid, generated oxygen-centred free radicals at concentrations≥10 µM, as determined by electron paramagnetic resonance spectrometry (EPR). Interestingly, the tested phenolics offered significant protection to human umbilical endothelial cells (HUVECs) against chemically induced oxidative stress. The protective effect of both phenolics were hormesic in profile; supraphysiological concentrations (100 µM) were cytotoxic, whereas physiologically relevant concentrations (100 nM – 1 µM) were protective against oxidative stress. The observed protection was associated with increased intracellular glutathione.

The results confirm that physiologically relevant concentrations of delphinidin and its major metabolite, gallic acid, are sufficient to induce antioxidant benefits, but via an indirect, xenobiotic mechanism that induces upregulation of endogenous antioxidant capacity. The findings emphasis that stability, rate of absorption, distribution and metabolism of phenolic compound needs to be taken into consideration when designing in vitro studies to test their mechanism of action.

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