Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism.

Nutraceuticals act as cellular and functional modulators, contributing to the homeostasis of physiological processes. In an inflammatory microenvironment, these functional foods can interact with the immune system by modulating or balancing the exacerbated proinflammatory response. In this process, immune cells, such as antigen-presenting cells (APCs), identify danger signals and, after interacting with T lymphocytes, induce a specific effector response. Moreover, this conditions their change of state with phenotypical and functional modifications from the resting state to the activated and effector state, supposing an increase in their energy requirements that affect their intracellular metabolism, with each immune cell showing a unique metabolic signature. Thus, nutraceuticals, such as polyphenols, vitamins, fatty acids, and sulforaphane, represent an active option to use therapeutically for health or the prevention of different pathologies, including obesity, metabolic syndrome, and diabetes. To regulate the inflammation associated with these pathologies, intervention in metabolic pathways through the modulation of metabolic energy with nutraceuticals is an attractive strategy that allows inducing important changes in cellular properties. Thus, we provide an overview of the link between metabolism, immune function, and nutraceuticals in chronic inflammatory processes associated with obesity and diabetes, paying particular attention to nutritional effects on APC and T cell immunometabolism, as well as the mechanisms required in the change in energetic pathways involved after their activation.

Dendritic cells: the yin and yang in disease progression.

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the "yin-yang" role of DCs to improve the understand of this type of cells in disease progression.

The renoprotective effect of L-carnitine in hypertensive rats is mediated by modulation of oxidative stress-related gene expression.

PURPOSE: Arterial hypertension is associated with a high production of reactive oxygen species and a decrease in the antioxidant defense systems. Based on the lack of toxicity of L-carnitine (LC) and previous studies reporting beneficial effects of this compound in experimental models of hypertension, the aim of this work was to test the hypothesis that LC might protect the kidney against hypertension-induced oxidative damage, as well as to investigate the mechanisms involved in this effect. To this end, specific activities and protein/mRNA expression of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, and superoxide dismutase), and those of NADPH oxidase (the main responsible for superoxide anion production in renal tissue) have been measured in renal cortex homogenates from NG-nitro-L-arginine methyl ester (L-NAME)-treated rats and control normotensive rats. In addition, components of the renin-angiotensin system (RAS) and redox-sensitive transcription factors (NF-κB, Nrf2, and PPARα) have also been evaluated. METHODS: Male Wistar rats aged 6-8 weeks were divided into four groups of six animals each: (1) control, normotensive Wistar rats (with free access to tap water); (2) Wistar rats subjected to treatment with 25 mg of L-NAME/kg body weight/day dissolved in the drinking water, in order to develop L-NAME-induced hypertension; (3) Wistar rats subjected to treatment with 400 mg of LC/kg body weight/day (also dissolved in the drinking water); and (4) L-NAME-treated rats subjected to simultaneous treatment with LC at the indicated doses. RESULTS: The beneficial effect of LC supplementation on oxidative damage in the renal cortex of hypertensive rats reversed hypertension-associated renal function damage and produced an upregulation of both antioxidant enzymes and eNOS, and with a downregulation of both NADPH oxidase and RAS components. LC improves the oxidative stress response through a specific modulation of NF-κB, Nrf2, and PPARα transcription factors. Thus, the low production of superoxide anions, subsequent to NADPH oxidase inhibition, might act by increasing the expression of Nrf2 and PPARα and by decreasing that of NF-κB, which, in turn, would enhance the antioxidant defense systems. CONCLUSIONS: Our results might support the use of LC to prevent hypertension-induced renal damage.