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Stress-related psychological ill health has increased dramatically in Europe. A diagnosis equivalent to occupational burnout can be found in the Swedish version of the tenth edition of the “International Statistical Classification of Diseases and Related Health Problems" by the World Health Organization. The Swedish National Board of Health and Welfare lists treatment suggestions including a section of self-care that recommended something that could be translated to “a sensible diet” (“vettig kost”) without providing evidence for what could constitute a sensible diet. By using the hypothesis of burnout being a stress-mediated decrease in neurogenesis which in turn decrease the ability to cope with stress, this article systematically reviews the efficacy of dietary polyphenols on neurogenesis in rodents to evaluate if dietary polyphenols could constitute a part of a sensible diet for burnout patients. Dietary polyphenols significantly increased various parts of neurogenesis, in rodents subjected to stressors, in some cases demonstrating effect sizes comparable to antidepressants. Adverse effects have been observed in extremely high doses and young rodents not exposed to induced stressors with a putative high level of neurogenesis.

Polyphenols are naturally-occurring phytochemicals, which form an integral part of the human diet. Results from epidemiological studies have associated polyphenol intake with reduced risk of cardiovascular diseases. Previous human intervention studies suggested that dietary polyphenols exert their cardioprotective effects through their antioxidant and anti-inflammatory effects. While most in vitro experiments have not accounted for the bioavailability and metabolism of these polyphenols, our work has provided direct evidence, using quercetin, that metabolic transformation, together with bioavailability, exert profound effects on bioactivity. We examined the effect of quercetin and its major metabolites on the production of pro-inflammatory eicosanoids by human leukocytes. Studies comparing free radical scavenging, antioxidant activity and eicosanoid production demonstrate that there are different structural requirements for antioxidant and anti-inflammatory activity. We also investigated the effect of metabolic transformation on flavonoid bioactivity by comparing the activity of quercetin and its major metabolites to inhibit inflammatory eicosanoid production from human leukocytes. Quercetin was a potent inhibitor of leukotriene B4 formation in leukocytes (IC50 ~ 2µM), and its activity was dependent on specific structural features, particularly the 2,3 double bond of the C ring. Functionalisation of the 3'-OH group with either methyl or sulfate reduced inhibitory activity up to 50% while a glucuronide substituent at the 3-OH effectively removed the leukotriene B4 inhibitory activity. The major quercetin metabolite quercetin-3'-O-sulfate retained considerable lipoxygenase inhibitory activity (IC50 ~ 7 µM) while quercetin-3-O-glucuronide maintained antioxidant activity but had no lipoxygenase inhibitory activity at physiologically relevant concentrations. We conclude that structural modification of quercetin due to metabolic transformation had a profound effect on bioactivity, and that the structural features required for antioxidant activity of 8 quercetin and related flavonoids were unrelated to those required for inhibition of inflammatory eicosanoids.

In this review we discuss the inhibitory effects of dietary polyphenols and amphibian antimicrobial/antitumor peptides on ATP synthase. In the beginning general structural features highlighting catalytic and motor functions of ATP synthase will be described. Some details on the presence of ATP synthase on the surface of several animal cell types, where it is associated with multiple cellular processes making it an interesting drug target with respect to dietary polyphenols and amphibian antimicrobial peptides will also be reviewed. ATP synthase is known to have distinct polyphenol and peptide binding sites at the interface of α/β subunits. Molecular interaction of polyphenols and peptides with ATP synthase at their respective binding sites will be discussed. Binding and inhibition of other proteins or enzymes will also be covered so as to understand the therapeutic roles of both types of molecules. Lastly, the effects of polyphenols and peptides on the inhibition of Escherichia coli cell growth through their action on ATP synthase will also be presented.