For the treatment of neurological disorders, polyphenols in Vaccinium berry species may be an effective addition to standard medicinal products. Polyphenols may reduce oxidative stress and inflammation, processes believed to contribute to disorders such as Parkinson’s disease. We performed an analysis of polyphenol content, biochemical attributes and neurobiological activity of extracts from wild blueberries native to Newfoundland and Labrador. Fruits and leaves of samples contained several polyphenolic compounds, such as anthocyanins, and demonstrated high antioxidant capacity. Cell cultures of microglia, the innate immune cells of the brain, were exposed to glutamate or α-synuclein in order to induce inflammatory responses, which decreased the amount of cells after 24 h. Overall, treatment of cells with fruit or leaf extracts inhibited cell death and decreased morphological criteria associated with inflammation. These results suggest that dietary intake of blueberry fruits and leaves or supplements may be protective against neurodegenerative disorders that include a neuroinflammatory component.

Alternative oxidase (AOX) is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain (ETC) that has a lower affinity for oxygen than does cytochrome (cyt) oxidase. To investigate the role(s) of AOX under different oxygen conditions, wild-type (WT) Nicotiana tabacum plants were compared with AOX knockdown and overexpression plants under normoxia, hypoxia (near-anoxia), and during a reoxygenation period following hypoxia. Paradoxically, under all the conditions tested, the AOX amount across plant lines correlated positively with leaf energy status (ATP/ADP ratio). Under normoxia, AOX was important to maintain respiratory carbon flow, to prevent the mitochondrial generation of superoxide and nitric oxide (NO), to control lipid peroxidation and protein S-nitrosylation, and possibly to reduce the inhibition of cyt oxidase by NO. Under hypoxia, AOX was again important in preventing superoxide generation and lipid peroxidation, but now contributed positively to NO amount. This may indicate an ability of AOX to generate NO under hypoxia, similar to the nitrite reductase activity of cyt oxidase under hypoxia. Alternatively, it may indicate that AOX activity simply reduces the amount of superoxide scavenging of NO, by reducing the availability of superoxide. The amount of inactivation of mitochondrial aconitase during hypoxia was also dependent upon AOX amount, perhaps through its effects on NO amount, and this influenced carbon flow under hypoxia. Finally, AOX was particularly important in preventing nitro-oxidative stress during the reoxygenation period, thereby contributing positively to the recovery of energy status following hypoxia. Overall, the results suggest that AOX plays a beneficial role in low oxygen metabolism, despite its lower affinity for oxygen than cytochrome oxidase.

Several species of berries, such as blueberries (Vaccinium angustifolium) and lingonberries (Vaccinium vitis-idaea L.), have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed metabolic mechanisms to survive various environmental stresses, some of which involve reactive oxygen species. In addition, the fruits and leaves of berries have high amounts of polyphenols, such as flavonoids, which act as potent antioxidants. These compounds could potentially be beneficial for brain aging and neurodegenerative disorders. There are now several studies documenting the beneficial effects of various berries in cell models of neurotoxicity as well as in vivo models of neurodegenerative disease. In the current review, we discuss the metabolic strategies that plants and animals have developed in order to combat reactive oxygen species. We then discuss issues of bioavailability of various compounds in mammals and provide a synopsis of studies demonstrating the neuroprotective ability of berries and polyphenols. We also summarize findings from our own research group. For example, we have detected various polyphenols in samples of blueberries and lingonberries and have found that the leaves have a much higher antioxidant capacity than the fruits. Extracts from these species have also demonstrated neuroprotective effects in cellular models of toxicity and inflammation, which are being further pursued in animal models.

Vyas, P., Curran, N. H., Igamberdiev, A. U. and Debnath, S. C. 2015. Antioxidant properties of lingonberry (Vaccinium vitis-idaea L.) leaves within a set of wild clones and cultivars. Can. J. Plant Sci. 95: 663–669. The antioxidant activities and the contents of total soluble phenolics, flavonoids, anthocyanins and proanthocyanidins were studied in wild and cultivated lingonberries (Vaccinium vitis-idaea L.). The antioxidant properties of wild clones were much higher than those of the cultivars. The levels of antioxidant compounds were positively correlated with latitude, altitude, reduced temperature and increased precipitation of the collected sites.

Berry fruits are known for their high antioxidant potential pertaining to their high phenolic content. Antioxidant capacities and phenolic content of blueberry and lingonberry fruits and leaves were studied. Concentrations of total flavonoids, tannins, proanthocyanidin as well as reduced and oxidized levels of ascorbate and glutathione were also determined in these extracts. This study also determined the potential neuroprotective effect of extracts from fruits and leaves against glutamate-mediated excitotoxicity, which is believed to contribute to disorders such as stroke and neurodegenerative diseases. Brain-derived cell cultures from rats were prepared and grown for about 2 weeks. Cell cultures were treated with glutamate (0.1 mM) for 24 h, and the effect of extracts was determined on cells subjected to this excitotoxicity. Blueberry fruits and leaves from both the extracts showed a significant neuroprotective effect. In this study we have shown how phenolic compounds as well as reduced and oxidized levels of ascorbate and glutathione correlate with neuroprotective effect.

Phenolic compounds are a large class of phytochemicals that are widespread in the plant kingdom and known to have antioxidant capacities. This study aimed to determine the antioxidant capacities as well as the content of total soluble phenolics, anthocyanins, tannins, and flavonoids in the fruits and leaves of blueberries and lingonberries growing in Newfoundland. This study also determined the potential neuroprotective effect of extracts from fruits and leaves against glutamate-mediated excitotoxicity, which is believed to contribute to disorders such as stroke and neurodegenerative diseases. Lingonberry and blueberry plants were found to be rich sources of phenolic compounds. Total antioxidant capacities in terms of radical scavenging activity and reducing power were much higher in leaves of both plants as compared to their fruits. These results were in correlation with phenolic contents including total flavonoids, anthocyanins, and tannins. Brain-derived cell cultures from rats were prepared and grown for about 2 weeks. Cell cultures were treated with glutamate (100 μM) for 24 h, and the effect of extracts was determined on cells subjected to this excitotoxicity. Glutamate treatment caused approximately 23% cell loss when measured after 24 h of exposure. Whereas lingonberry fruit extract did not provide protection from glutamate toxicity, blueberry fruit extracts were extremely protective. Leaf extracts of both lingonberry and blueberry showed a significant neuroprotective effect. The greater protective effect of leaf extracts was in correlation with the levels of phenolics and antioxidant capacity. These findings suggest that berries or their components may contribute to protecting the brain from various pathologies.