Neuroprotective effects of anthocyanidins on astrocytes and apoptosis induced by oxidative damage

As a result of the longer life expectancy in human population, neurodegenerative diseases such as Alzheimer's or Parkinson's diseases are increasing so the finding of effective treatments together with prevention strategies are urgently needed. Anthocyanins are polyphenolic compounds that can be found in several vegetal species and have shown strong antioxidant and anti-inflammatory activities in various experimental models. The effect of the anthocyanidins cyanidin, malvidin and pelargonidin at different concentrations (5 to 100µM) on experimental models of cell oxidation and apoptosis is studied. The human astrocyte glioblastoma, cellular line U373, was used for a cellular injury model using Fenton's reagent (FeSO₄ 0,5 mM/H₂O₂ 1 mM) and to measure the lactate dehydrogenase (LDH) enzyme activities and lipid peroxidation level (thiobarbituric acid reactive substances -TBARS) by fluorimetric analysis and malondialdehyde (MDA) release by HPLC)[1]. Also, caspase-3, -8 and -9 activities were measured by flurometric analysis. Results show that the studied anthocyanidins are able to revert the induced apoptosis related to caspase activation (Figure 1) and lipid peroxidation [3] (Figure 2). Cyanidin and pelargonidin at the highest doses induce a direct damage on astrocytes culture, as deduced from the LDH values when compared with non-treated cells; this effect seems to be independent of the protective activity against lipid peroxidation. All the assayed anthocyanidins significantly decrease the activation of caspases 8 and -3 previously induced by H₂O₂ (500µM), however malvidin and cyanidin increased the activation of caspase-9 when compared to non-treated cells; nonetheless, this increased activity was not related to an increase in performer caspase-3 which could be related to other cell homeostatic functions different from apoptosis induction in cells studied [2].

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Fig. 2

Keywords: anthocyanidins, neuroprotection, astrocytes, caspase, MDA

References:

[1] Grotto, D. et al. (2007)J Pharm Biomed Anal. 2007; 43: 619 – 24.

[2] Connolly, P.F. et al (2014) Front Physiol, doi: 10.3389/fphys.2o14.00149.