Avocado Paste Phenolics Mitigate a High-Fat Diet-Induced Plasma HDL Decrease in Male Wistar Rats, by Altering the mRNA Expression of Hepatic SCARB1.

Avocado paste (AP) is the main industrial byproduct of its processing, and retains various phenolic compounds (PCs). PCs are known to normalize the plasma lipid profile, but those from avocado byproducts have been minimally studied. We report the normalizing effects of an AP-derived phenolic extract (PE) on the plasma lipid profile of male Wistar rats. A standard (SD) and high-fat diet (HFD) were formulated, and the same diets were supplemented with 1 g/kg of diet of PE (SD + PE and HFD + PE). Rats were fed these diets during an 8-week period. The HFD induced signs of dyslipidemia, but PE treatment countered the decrease in HDL. Relative mRNA expression (real-time PCR) of the hepatic HDL receptor (SCARB1) increased in both groups (SD + PE and HFD + PE), while the LDR receptor (LDLR) increased in SD + PE group. The mRNA expression of apolipoproteins APOA1 and APOB was unaffected. We conclude that PCs from AP can counter a diet-induced decrease in plasma HDL by acting on the mRNA expression of its hepatic receptor.

N-(levodopa) chitosan derivative based on click chemistry shows biological functionality in brain cells.

OBJECTIVE: To develop N-(levodopa) chitosan derivatives through click chemistry to study their effect in brain cells.Significance: This study presents a proof-of-concept that macromolecules such as N-(Levodopa) chitosan derivatives traverse brain cell membranes and induce biomedical functionalities. METHODS: Through click chemistry, we developed N-(levodopa) chitosan derivatives. They were physically and chemically characterized by FT-IR, 1H-NMR, TGA and Dynamic Light Scattering analyses. Solution and nanoparticles of N-(levodopa) chitosan derivatives were tested in primary cell cultures from the postnatal rat olfactory bulb, substantia nigra and corpus callosum. Ca2+ imaging and UPLC experiments were used to investigate if the biomaterial modulated the brain cell physiology. RESULTS: N-(levodopa) chitosan derivatives induced intracellular Ca2+ responses in primary cell cultures of the rat brain. UPLC experiments indicated that levodopa attached to chitosan was converted into dopamine by brain cells. CONCLUSION: The present study shows that N-(levodopa) chitosan may be useful to develop new treatment strategies, which could serve as molecular reservoirs of biomedical drugs to treat degenerative disorders of the nervous system.

Phenolic compounds can induce systemic and central immunomodulation, which result in a neuroprotective effect.

Inflammation may negatively impact health, particularly that of the central nervous system. Phenolic compounds are bioactive molecules present in fruits and vegetables with potential anti-inflammatory effects. The purpose of the present work is to review the immunomodulatory bioactivities of phenolic compounds in the periphery and in the central nervous system. Results show that various types of phenolics are able to counter diet- or pathogen-induced systemic inflammation (among others) in various models. In vitro data show significant effects of flavonoids and phenolic acids in particular; similar bioactivities were reported in vivo, when administering them as pure compounds or from fruit and vegetable extracts that contain them. In the central nervous system, phenolics counter chronic inflammation and aggressive acute inflammatory processes, such as ischemic events, when administered preemptively and even therapeutically. We therefore conclude that the immunomodulatory potential of phenolic compounds can maintain an adequate immune response; their regular consumption should therefore be prioritized in order to maintain health. PRACTICAL APPLICATIONS: The immune response must be carefully regulated in order to avoid its deleterious effects. The present work highlights how phenolic compounds, dietary components ubiquitous in everyday diet, are able to maintain it within an adequate range. As humans are exposed to more proinflammatory stimuli (inadequate dietary pattern, mental stress, environmental pollution, chronic diseases, etc.), it becomes necessary to counter them, and consuming adequate amounts of foods that contain compounds with this ability is a rather simple strategy. Thus, the present work highlights how fruits and vegetables can help to maintain an adequate immune response that can preserve systemic health and that of the central nervous system. Furthermore, specific compounds contained in them can also be ideal candidates for additional in-depth studies, which can potentially lead to the development of potent, targeted, and safe anti-inflammatory molecules.

Mango "Ataulfo" Peel Extract Improves Metabolic Dysregulation in Prediabetic Wistar Rats.

The hypoglycemic effect of functional phytochemicals has been evaluated in diabetic rodents but scarcely in its premorbid condition (prediabetes; PD). This study aimed to evaluate a mango (cv. Ataulfo) peel hydroethanolic (20:80) extract (MPE) for in vivo glycemic/lipidemic-normalizing effect and in vitro enzyme inhibitory (α-amylase/α-glucosidase) activity. The polyphenolic MPE (138 mg EAG.g−1, mainly gallic acid and mangiferin) with antioxidant capacity (DPPH• 34 mgTE.g−1) was fed to PD rats (induction: high-fat diet (60% energy) + single dose streptozotocin (35 mg·kg−1), 4 weeks). At the 8th week, fasting glycemia (FG), oral glucose tolerance test, and insulin sensitivity indexes (HOMA-IR, HOMA-ß) > blood lipid-normalizing effect were documented as healthy controls > MPE > disease (PD) controls, which was possibly related to the extract's concentration−response in vitro enzyme inhibitory activity (IC50 ≈ 0.085 mg·mL−1). MPE is a rich source of glucose-lowering phytochemicals for the primary prevention of type 2 diabetes.

Sub-chronic consumption of a phenolic-rich avocado paste extract induces GLP-1-, leptin-, and adiponectin-mediated satiety in Wistar rats.

Avocado paste (AP) is a phenolic-rich byproduct of avocado oil extraction. The effects of sub-chronic consumption of diets supplemented with an AP phenolic extract (PE) were analyzed. A standard diet (SD), high-fat diet (HFD), and these supplemented with PE (SD + PE and HFD + PE) were used. Significantly increased satiety was observed in PE-supplemented groups, according to less food consumption (-15% in SD + PE vs. SD, and -11% in HFD + PE vs. HFD), without changes in weight gain or percentage of adipose tissue. PE-supplemented groups had an increased plasma concentration ( + 16% in SD + PE vs. SD, and +26% in HFD + PE vs. HFD) and relative mRNA expression (+74% in SD + PE vs. SD, and +46% in HFD + PE vs. HFD) of GLP-1; an increase in plasma leptin and adiponectin was independent of their mRNA expression. Our results suggest that AP-derived PE exerts a satiety effect in vivo, possibly mediated by GLP-1, leptin, and adiponectin. PRACTICAL APPLICATIONS: Minimizing food waste is a top priority in most of the world, thus, researchers seek methods to reintroduce industrial fruit and vegetable byproducts into the food processing chain. The present work highlights the potential of avocado byproducts as sources of bioactive phenolic compounds, whose sub-chronic consumption (8 weeks) exerts a satiety action in vivo. Avocado farming is resource-intensive, making it of relevance to producers and processing industries to avoid discarding its byproducts as much as possible.

Phenolic compounds that cross the blood-brain barrier exert positive health effects as central nervous system antioxidants.

The blood-brain barrier (BBB) is a physical structure whose main function is to strictly regulate access to circulating compounds into the central nervous system (CNS). Vegetable-derived phenolic compounds have been widely studied, with numerous epidemiologic and interventional studies confirming their health-related bioactivities across multiple cells, organs and models. Phenolics are non-essential xenobiotics, and should theoretically be unable to cross the BBB. The present work summarizes current experimental evidence that reveals that not only are phenolic compounds able to cross the BBB and bioaccumulate in the brain, but there is some stereoselectivity, which suggests the presence of specific transporters that allow them to reach the brain. Some molecules cross the BBB intact, while others do so only after being biotransformed or metabolized elsewhere. Once inside the CNS, they prevent or counter oxidative stress, which maintains the molecular, cellular, structural and functional integrity of the brain, and subsequently, overall human health.

Angiotensin II, ATP and high extracellular potassium induced intracellular calcium responses in primary rat brain endothelial cell cultures.

The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. This work investigated in vitro if BECs from the meninges from rat forebrain respond to ATP, angiotensin II and high extracellular potassium, with intracellular calcium mobilizations and its second messenger-associated pathways. We found that in primary BEC cultures, both ATP and angiotensin II produced intracellular calcium responses linked to the activation of inositol trisphosphate receptors and ryanodine receptors, which led to calcium release from intracellular stores. We also used RT-PCR to explore what potassium channel subunits are expressed by primary BEC cultures and freshly isolated meningeal tissue, and which might be linked to the observed effects. We found that BECs mainly expressed the inward rectifier potassium channel subunits Kir1.1, Kir3.3, Kir 4.1 and Kir6.2. This study contributes to the understanding of the functions elicited by ATP and angiotensin II in BECs from rat meninges. SIGNIFICANCE OF THE STUDY: Brain endothelial cells (BECs) express diverse ion channels and membrane receptors, which they might use to communicate with neurons and glia. This work investigated in vitro, if BECs from the rat forebrain respond to angiotensin II and ATP with intracellular calcium mobilizations. We found that these cells did respond to said substances with intracellular calcium mobilizations linked to inositol trisphosphate and ryanodine receptor activation, which led to calcium release from intracellular stores. These findings are important because they might uncover routes of active communication between brain cells and endothelial cells.

Neuroprotective effects of mango cv. 'Ataulfo' peel and pulp against oxidative stress in streptozotocin-induced diabetic rats.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis and progression of diabetes mellitus. Both can damage the brain. Mango and its by-products are sources of bioactive compounds with antioxidant properties. We hypothesized that mango cv. 'Ataulfo' peel and pulp mitigate oxidative stress in the brain of streptozotocin-induced diabetic rats. RESULTS: Twenty-four male Wistar rats were divided into four groups: control, untreated diabetic (UD), diabetic treated with a mango-supplemented diet (MTD), and diabetic pretreated with a mango-supplemented diet (MPD). The rats were fed the different diets for 4 weeks after diabetes induction (MTD), or 2 weeks before and 4 weeks after induction (MPD). After the intervention, serum and brain (cerebellum and cortex) were collected to evaluate gene expression, enzyme activity, and redox biomarkers. Superoxide dismutase 2 (SOD2) expression increased in the cortex of the MTD group, whereas glutathione-S-transferase p1 (GSTp1) expression was higher in the cortex of the MTD group, and cortex and cerebellum of the MPD group. SOD1 activity was higher in the cerebellum and cortex of all diabetic groups, whereas GST activity increased in the cerebellum and cortex of the MPD group. Lipid peroxidation increased in the cerebellum and cortex of the UD group; however, a mango-supplemented diet prevented this increase in both regions, while also mitigating polyphagia and weight loss, and maintaining stable glycemia in diabetic rats. CONCLUSION: We propose that mango exerts potent neuroprotective properties against diabetes-induced oxidative stress. It can be an alternative to prevent and treat biochemical alterations caused by diabetes. © 2020 Society of Chemical Industry.

Phenolic Compounds Promote Diversity of Gut Microbiota and Maintain Colonic Health.

The role of non-energy-yielding nutrients on health has been meticulously studied, and the evidence shows that a compound can exert significant effects on health even if not strictly required by the organism. Phenolic compounds are among the most widely studied molecules that fit this description; they are found in plants as secondary metabolites and are not required by humans for growth or development, but they can influence a wide array of processes that modulate health across multiple organs and systems. The lower gastrointestinal tract is a prime site of action of phenolic compounds, namely, by their effects on gut microbiota and colonic health. As with humans, phenolic compounds are not required by most bacteria but can be substrates of others; in fact, some phenolic compounds exert antibacterial actions. A diet rich in phenolic compounds can lead to qualitative and quantitative effects on gut microbiota, thereby inducing indirect health effects in mammals through the action of these microorganisms. Moreover, phenolic compounds may be fermented by the gut microbiota, thereby modulating the compounds bioactivity. In the colon, phenolic compounds promote anti-inflammatory, anti-oxidant and antiproliferative actions. The aim of the present review is to highlight the role of phenolic compounds on maintaining or restoring a healthy microbiota and overall colonic health. Mechanisms of action that substantiate the reported evidence will also be discussed.

Chitosan Derivatives: Introducing New Functionalities with a Controlled Molecular Architecture for Innovative Materials.

The functionalization of polymeric substances is of great interest for the development of innovative materials for advanced applications. For many decades, the functionalization of chitosan has been a convenient way to improve its properties with the aim of preparing new materials with specialized characteristics. In the present review, we summarize the latest methods for the modification and derivatization of chitin and chitosan under experimental conditions, which allow a control over the macromolecular architecture. This is because an understanding of the interdependence between chemical structure and properties is an important condition for proposing innovative materials. New advances in methods and strategies of functionalization such as the click chemistry approach, grafting onto copolymerization, coupling with cyclodextrins, and reactions in ionic liquids are discussed.

N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres.

Ion currents induced by ATP and angiotensin II in cultured follicular cells of Xenopus laevis.

Xenopus laevis oocytes are commonly used to study the biophysical and pharmacological properties of foreign ion channels and receptors, but little is known about those endogenously expressed in their enveloping layer of follicular cells (FCs). Whole-cell recordings and the perforated patch-clamp technique in cultured FCs held at -60 mV revealed that ATP (20-250 µM) generates inward currents of 465 ± 93 pA (mean ± standard error) in ~60% of the FCs studied, whereas outward currents of 317 ± 100 pA were found in ~5% of the cells. The net effect of ATP on the FCs was to activate both mono- and biphasic inward currents, with an associated increase in membrane chloride conductance. Two-microelectrode voltage-clamp recordings of nude oocytes held at -60 mV disclosed that ATP elicited biphasic inward currents, corresponding to the well-known F(in) and S(in)-like currents. ATP receptor antagonists like suramin, TNP-ATP, and RB2 did not inhibit any of these responses. On the other hand, when using whole-cell recordings, 1 µM Ang II yielded smooth inward currents of 157 ± 45 pA in ~16% of the FC held at -60 mV. The net Ang II response, mediated by the activation of the AT(1) receptor, was a chloride current inhibited by 10 nM ZD7155. This study will help to better understand the roles of ATP and Ang II receptors in the physiology of X. laevis oocytes.

Current profiles of astrocytes from the corpus callosum of newborn and 28-day-old rats.

In astrocytes, ion currents are predominantly carried by K(+) ions, and their potassium channel expression changes during development. Here, we studied ion current generated by voltage-ramp protocols in cultured astrocytes from the corpus callosum of newborn (P0) and 28-day-old (P28) rats. Inward currents measured at -140 mV and chord conductances measured from -140 to -75 mV, were smaller in P0-astrocytes than in P28-astrocytes, and in P28-astrocytes were affected by 100 µM Ba(2+), indicating the presence of an inward rectifier K(+) (Kir) current. On the other hand, P0-astrocytes showed higher outward current measured at 80 mV and a higher chord conductance, between 0 and 80 mV, than P28-astrocytes. The outward current was more potently reduced by 2mM Ba(2+) in P0-astrocytes than in P28-astrocytes, and slightly reduced at both ages using low concentrations of Ba(2+). Moreover, outward current was partially blocked by iberiotoxin in P0-astrocytes, indicating the presence of big-conductance Ca(2+)-activated K(+) (BK) channels. In addition, 4-aminopyridine inhibited the outward current in P0- and P28-astrocytes. In summary, P0-astrocytes exhibited the BK current, a major density of delayed rectifier K(+) (K(DR)) current, and a low density of the Kir current, whereas P28-astrocytes presented a major density of Kir current, a low density of the K(DR) current, and the absence of BK current. These results could contribute to a better understanding of the role of K(+) currents in the corpus callosum.

Membrane currents elicited by angiotensin II in astrocytes from the rat corpus callosum.

The corpus callosum (CC) is the main white matter tract in the brain. It consists primarily of axons and glial cells. In the present work, membrane currents generated by angiotensin II (Ang II) in cultured astrocytes from the CC of newborn and 3-week-old rats were studied using the whole-cell voltage-clamp technique. After 4 days of culture, approximately 90% of cells were positive to glial fibrillary acidic protein (GFAP), indicating their astrocyte lineage. Ang II elicited inward currents in approximately 20% of cells and outward currents in approximately 4% of cells from the CC for newborn or 3-week-old rats. The main effect of Ang II on astrocytes from the newborn rat CC was a reduction of membrane conductance, by blocking of delayed rectifier K(+) currents in 96% of cells. However, no common action of Ang II was observed in cells from 3-week-old rat CC because the responses were quite variable, suggesting the participation of other ion currents. The partial agonist of AT(2) receptors, CGP-42112A, exerted effects on Ang II responses, whereas the AT(1) antagonist ZD7155 did not, suggesting that Ang II responses in CC astrocytes are predominantly mediated by activation of AT(2) receptors. This study is the first to show electrical responses generated by AT(2) receptors in glial cells from the rat central nervous system, and may help gain a better understanding of the functions of Ang II receptors in astrocytes from the rat CC in particular and of glial cells in general. (c) 2005 Wiley-Liss, Inc.

Physicochemical and nutritional characteristics of the fruit of Zizyphus sonorensis S. Wats (Rhamnaceae).

The nanche de la costa (Zizyphus sonorensis) fruit was partially characterized by physicochemical and nutritional analyses. This fruit has a homogenous size and color and low moisture content (47 g/100 g). The content of tannins and nickel of the edible portion might limit its use. However, nanche de la costa has important characteristics and potential to be considered as a food or feed source. The remarkable characteristics of the edible portion are high content of total (35 g/100 g) and soluble (0.6 g/100 g) dietary fiber, high level of copper (0.53 mg/100 g), iron (10 mg/100 g) and zinc (4.2 mg/100 g). The seed was distinguished by its high content of total dietary fiber (82.1 g/100 g), calcium (540 mg/100 g), copper (0.54 mg/100 g), chromium (1.1 mg/100 g) and zinc (4.5 mg/100 g). The moisture value is given in fresh weight basis and all other values are in dry weight basis.