Sergio Davinelli

Antioxidants as antidepressants: fact or fiction?

Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress pro-cesses might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression.Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds.The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a signif-icant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study.

Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

Alzheimers disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

Extending healthy ageing: nutrient sensitive pathway and centenarian population

Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.

A Randomized Clinical Trial Evaluating the Efficacy of an Anthocyanin-Maqui Berry Extract (Delphinol®) on Oxidative Stress Biomarkers.

Objective: Berries are a rich source of anthocyanins, and clinical data suggest that a polyphenol-rich diet may exert health-promoting effects by reducing oxidative stress. The aim of this study was to elucidate the effects of dietary supplementation with Delphinol (trademark owned by MNL Chile) standardized maqui berry (Aristotelia chilensis) extract on products of lipid peroxidation in healthy, overweight, and smoker subjects. Methods: In a double-blind, placebo-controlled design, 42 participants (age 45–65 years) consumed in random order either a standardized extract of maqui berry (162 mg anthocyanins) or a matched placebo, given 3 times daily for 4 weeks. The samples were collected at baseline, after the end of the supplementation, and 40 days after the end of the study. Primary outcome was the measure of oxidized low-density lipoprotein (Ox-LDL) and F2-isoprostanes in plasma and urine, respectively. Secondary outcomes included anthropometric measures, blood pressure, and lipid profile. Results: Delphinol supplementation was associated with reduced levels of Ox-LDL in the anthocyanin group compared to baseline (p < 0.05). There was also a decrease in urinary F2-isoprostanes (8-iso-prostaglandin F2α) at 4 weeks versus baseline in the Delphinol-supplemented group (p < 0.05). However, no differences in primary outcomes were evident at 40 days of follow-up. In the fourth week of the intervention, no significant differences were noted for anthropometric characteristics, ambulatory blood pressure, and lipid profile. Conclusions: Our observations suggest that dietary interventions with maqui berry extract may improve oxidative status (Ox-LDL and F2-isoprostanes) in healthy adults, overweight adults, and adult smokers.

Enhancement of mitochondrial biogenesis with polyphenols: combined effects of resveratrol and equol in human endothelial cells

Emerging evidence suggests that combinatorial action of numerous biologically active compounds may be a valuable source in a variety of therapeutic applications. Several nutraceuticals have demonstrated to augment the efficacy of pharmacological approaches or provide physiological benefit to improve age-related decline. Recently, the possibilities of anti-ageing interventions have multiplied also to ameliorate the mitochondrial alterations in ageing-associated diseases. In this report, we approached a novel treatment strategy by combining two bioactive dietary constituents (resveratrol and equol) to determine their effect on mitochondrial function. Taking into account that the biological activities of resveratrol and equol has been observed in a wide range of biological processes, they were selected to examine whether combining them would be more effective to modulate mitochondrial function. In HUVEC cells our results demonstrate that the co-administration of these natural products increased mitochondrial mass and mitochondrial DNA content. Additionally, combined use of both compounds increased SIRT1 enzymatic activity and induced mitochondrial biogenesis factors such as PGC1-α, TFAM and NRF-1. Therefore, identification of this novel synergism may provide a new perspective for future treatments aiming to modulate the mitochondrial activity with implications in maintaining endothelial function which is crucial in the regulation of immune response. Further studies to discover the molecular details of this crosstalk and to identify new combinations of active compounds affecting the mitochondrial function will be extremely beneficial to prevent mitochondrial decline.

Dietary phytochemicals and neuro-inflammaging: from mechanistic insights to translational challenges

An extensive literature describes the positive impact of dietary phytochemicals on overall health and longevity. Dietary phytochemicals include a large group of non-nutrients compounds from a wide range of plant-derived foods and chemical classes. Over the last decade, remarkable progress has been made to realize that oxidative and nitrosative stress (O&NS) and chronic, low-grade inflammation are major risk factors underlying brain aging. Accumulated data strongly suggest that phytochemicals from fruits, vegetables, herbs, and spices may exert relevant negative immunoregulatory, and/or anti-O&NS activities in the context of brain aging. Despite the translational gap between basic and clinical research, the current understanding of the molecular interactions between phytochemicals and immune-inflammatory and O&NS (IO&NS) pathways could help in designing effective nutritional strategies to delay brain aging and improve cognitive function. This review attempts to summarise recent evidence indicating that specific phytochemicals may act as positive modulators of IO&NS pathways by attenuating pro-inflammatory pathways associated with the age-related redox imbalance that occurs in brain aging. We will also discuss the need to initiate long-term nutrition intervention studies in healthy subjects. Hence, we will highlight crucial aspects that require further study to determine effective physiological concentrations and explore the real impact of dietary phytochemicals in preserving brain health before the onset of symptoms leading to cognitive decline and inflammatory neurodegeneration.

Influence of equol and resveratrol supplementation on health-related quality of life in menopausal women: A randomized, placebo-controlled study

OBJECTIVE This study was designed to evaluate the effects of equol and resveratrol supplementation on health-related quality of life (HRQoL) in otherwise healthy menopausal women with hot flashes, anxiety and depressive symptoms. METHODS Sixty recently menopausal women aged 50-55 years were randomized in a 12-week, placebo-controlled trial to receive 200mg of fermented soy containing 10mg of equol and 25mg of resveratrol (1 tablet/day). The primary outcome was the change in score on the Menopause Rating Scale (MRS), used to evaluate the severity of age-/menopause-related complaints. Additional outcome measures included the subject-reported score on the Hamilton Rating Scale for Depression (HAM-D) and Nottingham Health Profile (NHP), which was used specifically to assess sleep quality. RESULTS The symptoms assessed by the MRS improved during treatment in the active group. Comparison between placebo and treatment groups revealed statistically significant improvement in particular for dryness of vagina (-85.7%) (p<0.001), heart discomfort (-78.8%; p<0.001) and sexual problems (-73.3%; p<0.001). On the HAM-D significant improvements at week 12 were seen in work and activities (-94.1%) (p<0.001). Subjects treated with equol and resveratrol also had significant differences in the sleep domain of the NHP (p<0.001). CONCLUSION These findings provide evidence that 12 weeks of dietary supplementation with equol and resveratrol may improve menopause-related quality of life in healthy women.

Dose response biology of resveratrol in obesity

Obesity is a major health problem throughout the world, and it is increasing both in prevalence and severity. Pharmaceutical approaches developed for the treatment of obesity, despite short-term benefits, often are associated with rebound weight gain after the cessation of drug use and serious side effects deriving from the medication can occur. Resveratrol has been well recognized as an anti-obesity substance for its lipid-lowering function as well as calorie-restriction effect. This polyphenol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. From an hormetic standpoint, we will discuss the potential relevance of resveratrol in the management of obesity and related comorbid conditions, emphasizing its ability to control simultaneously various pathological mechanisms associated with obesity.

Synergistic Effect of L-Carnosine and EGCG in the Prevention of Physiological Brain Aging

The benefits of multi-target action are well established in a variety of pathological models. Many dietary supplements and nutraceuticals may be useful to slow age-related cognitive declines and the risk of developing neurodegenerative disease. L-Carnosine and EGCG are natural compounds that have received particular attention because of their potential role in modulating oxidative stress associated with aging and chronic conditions. The biological activities of these naturally occurring substances have frequently been used to prevent or reduce senile features; however they have never been evaluated as a combined treatment. In the present study we investigated the combined effect of L-Carnosine and EGCG on the activation of two stress-responsive pathways: HO-1 and Hsp72 (the inducible form of Hsp70), which play an important role in cytoprotection against oxidative stress-induced cell damage. We demonstrated that the neuroprotective effects of EGCG and L-Carnosine are achieved through the modulation of HO-1/Hsp72 systems. Furthermore, the combined action of both compounds resulted in a synergistic increase of HO-1 expression which suggests a crosstalk between the HO-1 and the Hsp72-mediated pathways. Our results indicate that the combined administration of EGCG and L-Carnosine would benefit the treatment and prevention of neurodegenerative diseases by reducing the neuronal damage caused by oxidative stress.

Cocoa Bioactive Compounds: Significance and Potential for the Maintenance of Skin Health

Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health.