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Quinoa (Chenopodium quinoa Willd., Amaranthaceae) is a grain-like, stress-tolerant food crop that has provided subsistence, nutrition, and medicine for Andean indigenous cultures for thousands of years. Quinoa contains a high content of health-beneficial phytochemicals, including amino acids, fiber, polyunsaturated fatty acids, vitamins, minerals, saponins, phytosterols, phytoecdysteroids, phenolics, betalains, and glycine betaine. Over the past 2 decades, numerous food and nutraceutical products and processes have been developed from quinoa. Furthermore, 4 clinical studies have demonstrated that quinoa supplementation exerts significant, positive effects on metabolic, cardiovascular, and gastrointestinal health in humans. However, vast challenges and opportunities remain within the scientific, agricultural, and development sectors to optimize quinoa's role in the promotion of global human health and nutrition.

The idea that alterations in the brain immunomodulation are critical for Alzheimer's disease (AD) pathogenesis provides the most integrative view on this cognitive disorder, considering that converging research lines have revealed the involvement of inflammatory processes in AD. We have proposed the damage signal hypothesis as a unifying scheme in that release of endogenous damage/alarm signals, in response to accumulated cell distress (dyslipidemia, vascular insults, head injury, oxidative stress, iron overload, folate deficiency), is the earliest triggering event in AD, leading to activation of innate immunity and the inflammatory cascade. Inflammatory cytokines play a dual role, either promoting neurodegeneration or neuroprotection. This equilibrium is shifted toward the neurodegenerative phenotype upon the action of several risk factors that trigger innate damage signals that activate microglia and the release of tumor necrosis factor-alpha, interleukin-6, and some trophic factors. In this neuroimmunomodulatory hypothesis we integrate different risk factors with microaglial activation and the resulting neuronal alterations and hyperphosphorylations of tau protein. The progression of AD, with slowly increasing damage in brain parenchyma preceding the onset of symptoms, suggests that tissue distress triggering damage signals drives neuroinflammation. These signals via toll-like receptors, receptors for highly glycosylated end products, or other glial receptors activate sensors of the native immune system, inducing the anomalous release of cytokines and promoting the neurodegenerative cascade, a hallmark of brain damage that correlates with cognitive decline.

We used a murine model of type II diabetes, which reproduces the major features of the human disease, and a number of cellular models to study the antidiabetic effect of ANC, a standardised anthocyanin-rich formulation from maqui berry (Aristotelia chilensis). We also isolated delphinidin 3-sambubioside-5-glucoside (D3S5G), a characteristic anthocyanin from maqui berry, and studied its antidiabetic properties. We observed that oral administration of ANC improved fasting blood glucose levels and glucose tolerance in hyperglycaemic obese C57BL/6J mice fed a high fat diet. In H4IIE rat liver cells, ANC decreased glucose production and enhanced the insulin-stimulated down regulation of the gluconeogenic enzyme, glucose-6-phosphatase. In L6 myotubes ANC treatment increased both insulin and non-insulin mediated glucose uptake. As with the ACN, oral administration of pure D3S5G dose-dependently decreased fasting blood glucose levels in obese C57BL/6J mice, and decreased glucose production in rat liver cells. D3S5G also increased glucose uptake in L6 myotubes and is at least partially responsible for ANC’s anti-diabetic properties.

Hyperinsulinemia as well as type II diabetes mellitus are among the risk factors for Alzheimer's disease (AD). However, the molecular and cellular basis that link insulin resistance disorders and diabetes with AD are far from clear. Here, we discuss the potential molecular mechanisms that may explain the participation of these metabolic disorders in the pathogenesis of AD. The human brain uses glucose as a primary fuel; insulin secreted by the pancreas cross the blood-brain barrier (BBB), reaching neurons and glial cells, and exerts a region-specific effect on glucose metabolism. Glucose homeostasis is critical for energy generation, neuronal maintenance, neurogenesis, neurotransmitter regulation, cell survival and synaptic plasticity. It also plays a key role in cognitive function. In an insulin resistance condition, there is a reduced sensitivity to insulin resulting in hyperinsulinemia; this condition persists for several years before becoming full-blown diabetes. Toxic levels of insulin negatively influence neuronal function and survival, and elevation of peripheral insulin concentration acutely increases its cerebrospinal fluid (CSF) concentration. Peripheral hyperinsulinemia correlates with an abnormal removal of the amyloid beta peptide (Abeta) and an increase of tau hyperphosphorylation as a result of augmented cdk5 and GSK3beta activities. This leads to cellular cascades that trigger a neurodegenerative phenotype and decline in cognitive function. Chronic peripheral hyperinsulinemia results in a reduction of insulin transport across the BBB and a reduced insulin signaling in brain, altering all of insulin's actions, including its anti-apoptotic effect. However, the increase in brain insulin levels resulting from its peripheral administration at optimal doses has shown a cognition-enhancing effect in patient with AD. Some drugs utilized in type II diabetes mellitus reduce cognitive impairment associated with AD. The link between insulin resistance and neurodegeneration and AD, and the possible therapeutic targets in preventing the insulin-resistance disorders are analyzed.

We describe the interactions of two benzimidazole derivatives, astemizole (AST) and lansoprazole (LNS), with anomalous aggregates of tau protein (neurofibrillary tangles). Interestingly, these compounds, with important medical applications in the treatment of allergies and gastrointestinal disorders respectively, specifically bind to aggregated variants of tau protein and to paired helical filaments isolated from brains of Alzheimer's disease (AD) patients. These ligands appear to be a powerful tool to tag brain-isolated tau-aggregates and heparin-induced polymers of recombinant tau. The interactions of AST and LNS with tau aggregates were assessed by classical radioligand assays, surface plasmon resonance, and bioinformatic approaches. The affinity of AST and LNS for tau aggregates was comparatively higher than that for amyloid-β polymers according to our data. This is relevant since senile plaques are also abundant but are not pathognomonic in AD patients. Immunochemical studies on paired helical filaments from brains of AD patients and surface plasmon resonance studies confirm these findings. The capacity of these drugs to penetrate the blood-brain barrier was evaluated: i) in vitro by parallel artificial membrane permeability assay followed by experimental Log P determinations; and ii) in vivo by pharmacokinetic studies comparing distribution profiles in blood and brain of mice using HPLC/UV. Importantly, our studies indicate that the brain/blood concentration ratios for these compounds were suitable for their use as PET radiotracers. Since neurofibrillary tangles are positively correlated with cognitive impairment, we concluded that LNS and AST have a great potential in PET neuroimaing for in vivo early detection of AD and in reducing the formation of neurofibrillary tangles.

Cinnamon has a long history of medicinal use and continues to be valued for its therapeutic potential for improving metabolic disorders such as type 2 diabetes. In this study, a phytochemically-enhanced functional food ingredient that captures water soluble polyphenols from aqueous cinnamon extract (CE) onto a protein rich matrix was developed. CE and cinnamon polyphenol-enriched defatted soy flour (CDSF) were effective in acutely lowering fasting blood glucose levels in diet-induced obese hyperglycemic mice at 300 and 600 mg/kg, respectively. To determine mechanisms of action, rat hepatoma cells were treated with CE and eluates of CDSF at a range of 1–25 µg/ml. CE and eluates of CDSF demonstrated dose-dependent inhibition of hepatic glucose production with significant levels of inhibition at 25 µg/ml. Furthermore, CE decreased the gene expression of two major regulators of hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. The hypoglycemic and insulin-like effects of CE and CDSF may help to ameliorate type 2 diabetes conditions.

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