Cocoa, the main derivative of the seeds of Theobroma cacao L., has been recognized to have several effects on human health including antioxidant and neuro- and cardio-protective effects, among others. These effects have been attributed mainly to its bioactive compounds. In this context, the aim of this work is to evaluate the nutritional composition, bioactive compounds (i.e., phenolic compounds, procyanidins and methylxanthines) and the antioxidant activity of seven different cocoas (alkalized and non-alkalized) from different origins (Peru, Venezuela, Ivory Coast, Dominican Republic, and West Africa). It represents the first stage of a larger project aiming to find high polyphenol cocoa-based nutritional strategies and related biomarkers that may potentiate brain plasticity and cognitive function. Cocoa powders were extracted by ultrasound-assisted technology, and the total phenolic content (TPC) was measured by Folin–Ciocalteu. Methylxanthines (caffeine and theobromine) and procyanidin contents were determined by HPLC-FLD-DAD, and the antioxidant activity was assessed through DPPH, ABTS and FRAP assays. Non-alkalized cocoas showed higher phenolic and procyanidin contents and higher antioxidant activity compared to the alkalized ones. A strongly significant (p < 0.05) positive correlation between the antioxidant activity and the TPC, especially with the total procyanidin content, but not with methylxanthines was found. In conclusion, the non-alkalized cocoas, especially the one from Peru, were the best candidates in terms of bioactive compounds. The cocoa from Peru had a TPC of 57.4 ± 14.4 mg of gallic acid equivalent/g d.w., 28,575.06 ± 62.37 µg of catechin equivalents/g d.w., and 39.15 ± 2.12 mg/g of methylxanthines. Further studies should be undertaken to evaluate its effect on brain plasticity and cognitive function.

Boosting brain health: Cocoa diet enhances hippocampal neurogenesis and BDNF expression, improving cognitive function.

(1) Background: Cocoa’s healthy benefits may be attributed to the potent antioxidant activity of cocoa polyphenols, mainly flavanols, which have been characterised as existing in a high concentration in cocoa. However, the phenolic composition of cocoa and cocoa-derived products is highly variable, and manufacturing processes might significantly reduce their phenolic content. For that reason, the full characterisation of cocoa and cocoa-derived products before evaluating their bioactivity is crucial. The aim of this review is to analyse the available evidence on the effect of flavanol-fortified cocoa-derived products on human health. (2) Methods: Forty-eight clinical trials focused on the health effect of consuming flavanol-fortified drinks, bars and chocolate have been reviewed, with a total of 1523 subjects. (3) Results: Although studies differ widely in methodology, dosage, duration, and target population, beneficial effects of flavanol-rich cocoa consumption have been observed at doses ranging from 45.3 mg/d to 1078 mg/d, especially on cardiovascular health and cognitive function. (4) Conclusions: Considering the high consumption and acceptability of cocoa and cocoa-derived products, the fortification of cocoa products as well as other highly consumed foods with cocoa flavanols could be an effective strategy for health promotion.

Genome-wide association studies (GWAS) constitute a powerful tool to identify the different biochemical pathways associated with disease. This knowledge can be used to prioritize drugs targeting these routes, paving the road to clinical application. Here, we describe DAGGER (Drug Repositioning by Analysis of GWAS and Gene Expression in R), a straightforward pipeline to find currently approved drugs with repurposing potential. As a proof of concept, we analyzed a meta-GWAS of 1.6 × 10⁷ single-nucleotide polymorphisms performed on Alzheimer’s disease (AD). Our pipeline uses the Genotype-Tissue Expression (GTEx) and Drug Gene Interaction (DGI) databases for a rational prioritization of 22 druggable targets. Next, we performed a two-stage in vivo functional assay. We used a C. elegans humanized model over-expressing the Aβ_1-42 peptide. We assayed the five top-scoring candidate drugs, finding midostaurin, a multitarget protein kinase inhibitor, to be a protective drug. Next, 3xTg AD transgenic mice were used for a final evaluation of midostaurin’s effect. Behavioral testing after three weeks of 20 mg/kg intraperitoneal treatment revealed a significant improvement in behavior, including locomotion, anxiety-like behavior, and new-place recognition. Altogether, we consider that our pipeline might be a useful tool for drug repurposing in complex diseases.

Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood–brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.

Prenatal ethanol exposure (PEE) alters fetal brain development, potentially increasing the risk of neurodegenerative diseases such as Alzheimer’s disease (AD) later in life. Although glial activation is implicated in AD pathology via cannabinoid and neuroinflammatory signaling, its potential response to PEE in the developing brain and its contribution to AD pathogenesis remain unknown. Using 3×Tg-AD offspring of both sexes born to mothers with PEE, we analyzed astrogliosis, inflammatory markers, and key components of cannabinoid and Ca²⁺ signaling in primary cultures of hippocampal astrocytes, elements whose dysfunction contributes to neurodegeneration. Our results indicated that PEE increased astrogliosis/inflammatory response (significant elevation of Gfap and Tnfα expression) in hippocampal astrocytes at birth. This neuroinflammation was significantly associated with lower expression of cannabinoid receptors (Cnr1 and Gpr55), and decreased concentrations of the anti-inflammatory lipid PEA in the culture medium, probably due to a deregulated endocannabinoid enzymatic machinery (NAPE-PLD/FAAH ratio). This research provides insights into GRP55/PEA-mediated signaling as a potential hippocampal astrocytic mechanism influenced by maternal ethanol exposure, which may contribute to neurobiological changes associated with increased vulnerability to AD-related pathology.