Abstract
Anthocyanins are considered as bioactive components of plant-based diets that provide protection against ischemic cardiovascular pathologies by mechanisms dependent on their antioxidant and reductive capacities. However, it is not clear whether similar anthocyanin-mediated mechanisms can provide protection against ischemia-induced brain mitochondrial injury and cell death. In this study, we compared effects of three cyanidin-3-glycosides – glucoside (Cy3G), galactoside (Cy3Gal) and rutinoside (Cy3R), with pelargonxidin-3-glucoside (Pg3G) and found that at 10–20 μM concentrations they have no direct effect on respiratory functions of mitochondria isolated from normal or ischemia-damaged rat brain slices. However, intravenous injection of Cy3Gal and Cy3G (0,025 mg/kg or 0,05 mg/kg what matches 10 μM or 20 μM respectively) but not Cy3R in rats protected against ischemia-induced caspase activation and necrotic cell death, and reduced infarct size in cerebral cortex and cerebellum. These effects correlated with cytochrome c reducing capacity of cyanidin-3-glycosides. In contrast, intravenous injection of 0,025 mg/kg Pg3G which has the lowest cytochrome c reducing capacity among investigated anthocyanins, had no effect on ischemia-induced caspase activation and necrosis but reduced brain infarct size whereas intravenous injection of 0,05 mg/kg of Pg3G slightly promoted necrosis in the brain. Our data suggest that reductive rather than antioxidant capacities of anthocyanins may be important components in providing protection against ischemic brain damage.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- Cy3G:
-
cyanidin-3-glucoside, anthocyanin
- Cy3Gal:
-
cyanidin-3-galactoside, anthocyanin
- Cy3R:
-
cyanidin-3-rutinoside, anthocyanin
- Pg3G:
-
pelargonidin-3-glucoside, anthocyanin
- AA:
-
ascorbic acid
- DHA:
-
dehydroascorbic acid
- LDH:
-
lactate dehydrogenase
- DEVD:
-
acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin
- TTC:
-
2,3,5,-triphenyltetrazolium chloride.
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This project has received funding from European Social Fund (project No 09.3.3-LMT-K-712-01-0131) under grant agreement with the Research Council of Lithuania (LMTLT).
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Authors’ contributions: VB designed the research, ER carried out the procedures with animals. KP and KS performed the experiments. All authors analyzed data and contributed to the final version of the manuscript.
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All experimental procedures were reviewed and approved by the National Ethical Committee for Animal Care (Lisences No 0217 and No 0228) according to Directive 86/609/EEC. The rats were maintained and handled at Lithuanian University of Health Sciences animal house in agreement with the Guide for the Care and Use of Laboratory Rats.
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Skemiene, K., Pampuscenko, K., Rekuviene, E. et al. Protective effects of anthocyanins against brain ischemic damage. J Bioenerg Biomembr 52, 71–82 (2020). https://doi.org/10.1007/s10863-020-09825-9
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DOI: https://doi.org/10.1007/s10863-020-09825-9