Method development with high-throughput enhanced matrix removal followed by UHPLC-QqQ-MS/MS for analysis of grape polyphenol metabolites in human urine.

Grape and grape derived products contain many bioactive phenolics which have a variety of impacts on health. Following oral ingestion, the phenolic compounds and their metabolites may be detectable in human urine. However, developing a reliable method for the analysis of phenolic compounds in urine is challenging. In this work, we developed and validated a new high-throughput, sensitive and reproducible analytical method for the simultaneous analysis of 31 grape phenolic compounds and metabolites using Oasis PRiME HLB cleanup for sample preparation combined with ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). Using this new method, the accuracy achieved was 69.3 % ∼ 134.9 % (except for six compounds), and the recovery achieved was 52.4 % ∼ 134.7 % (except for two very polar compounds). For each of the 31 target analytes, the value of intra-day precision was less than 14.3 %. The value of inter-day precision was slightly higher than intra-day precision, with a range of 0.7 % ∼ 19.1 %. We report for the first time on the effect of gender and BMI on the accuracy and recovery of human urine samples, and results from analysis of variance (ANOVA), and principal component analysis (PCA) indicated there was no difference in the value of accuracy and recovery between different gender or BMI (>30) using our purposed cleanup and UHPLC-QqQ-MS/MS method. Overall, this newly developed method could serve as a powerful tool for analyzing grape phenolic compounds and metabolites in human urine samples.

Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O2 consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.

Protective effects of polyphenol-rich extracts against neurotoxicity elicited by paraquat or rotenone in cellular models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O 2 consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction.

Acrolein: formation, health hazards and its controlling by dietary polyphenols.

Acrolein, a highly reactive toxic aldehyde, is a common dietary and environmental contaminant which can also be generated endogenously. Exposure to acrolein has been positively associated with some pathological conditions, such as atherosclerosis, diabetes mellitus, stroke, and Alzheimer's disease. At the cellular level, acrolein induces various harmful effects, particularly protein adduction and oxidative damages. Polyphenols are a group of secondary plant metabolites ubiquitously presented in fruits, vegetables, and herbs. Recent evidence has gradually solidified the protective role of polyphenols by working as acrolein scavengers and regulator of acrolein toxicities. This was largely attributed to the ability of polyphenols as antioxidants and sacrificial nucleophiles in trapping acrolein. This review discussed the exposure and toxicity of acrolein, summarized the known and anticipated contribution of polyphenols in ameliorating acrolein contamination and its health hazards.

Successive harvests affect the aromatic and polyphenol profiles of novel catnip (Nepeta cataria L.) cultivars in a genotype-dependent manner.

Introduction: Catnip (Nepeta cataria L.) produces volatile iridoid terpenes, mainly nepetalactones, with strong repellent activity against species of arthropods with commercial and medical importance. Recently, new catnip cultivars CR3 and CR9 have been developed, both characterized by producing copious amounts of nepetalactones. Due to its perennial nature, multiple harvests can be obtained from this specialty crop and the effects of such practice on the phytochemical profile of the plants are not extensively studied. Methods: In this study we assessed the productivity of biomass, chemical composition of the essential oil and polyphenol accumulation of new catnip cultivars CR3 and CR9 and their hybrid, CR9×CR3, across four successive harvests. The essential oil was obtained by hydrodistillation and the chemical composition was obtained via gas chromatography-mass spectrometry (GC-MS). Individual polyphenols were quantified by Ultra-High-Performance Liquid Chromatography- diode-array detection (UHPLC-DAD). Results: Although the effects on biomass accumulation were independent of genotypes, the aromatic profile and the accumulation of polyphenols had a genotype-dependent response to successive harvests. While cultivar CR3 had its essential oil dominated by E,Z-nepetalactone in all four harvests, cultivar CR9 showed Z,E-nepetalactone as the main component of its aromatic profile during the 1st, 3rd and 4th harvests. At the second harvest, the essential oil of CR9 was mainly composed of caryophyllene oxide and (E)-ß-caryophyllene. The same sesquiterpenes represented the majority of the essential oil of the hybrid CR9×CR3 at the 1st and 2nd successive harvests, while Z,E-nepetalactone was the main component at the 3rd and 4th harvests. For CR9 and CR9×CR3, rosmarinic acid and luteolin diglucuronide were at the highest contents at the 1st and 2nd harvest, while for CR3 the peak occurred at the 3rd successive harvest. Discussion: The results emphasize that agronomic practices can significantly affect the accumulation of specialized metabolites in N. cataria and the genotype-specific interactions may indicate differential ecological adaptations of each cultivar. This is the first report on the effects of successive harvest on these novel catnip genotypes and highlights their potential for the supply of natural products for the pest control and other industries.

Role of Polyphenol-Derived Phenolic Acid in Mitigation of Inflammasome-Mediated Anxiety and Depression.

Overexposure to mental stress throughout life is a significant risk factor for the development of neuropsychiatric disorders, including depression and anxiety. The immune system can initiate a physiological response, releasing stress hormones and pro-inflammatory cytokines, in response to stressors. These effects can overcome allostatic physiological mechanisms and generate a pro-inflammatory environment with deleterious effects if occurring chronically. Previous studies in our lab have identified key anti-inflammatory properties of a bioavailable polyphenolic preparation BDPP and its ability to mitigate stress responses via the attenuation of NLRP3 inflammasome-dependent responses. Inflammasome activation is part of the first line of defense against stimuli of different natures, provides a rapid response, and, therefore, is of capital importance within the innate immunity response. malvidin-3-O-glucoside (MG), a natural anthocyanin present in high proportions in grapes, has been reported to exhibit anti-inflammatory effects, but its mechanisms remain poorly understood. This study aims to elucidate the therapeutic potential of MG on inflammasome-induced inflammation in vitro and in a mouse model of chronic unpredictable stress (CUS). Here, it is shown that MG is an anti-pyroptotic phenolic metabolite that targets NLRP3, NLRC4, and AIM2 inflammasomes, subsequently reducing caspase-1 and IL-1ß protein levels in murine primary cortical microglia and the brain, as its beneficial effect to counteract anxiety and depression is also demonstrated. The present study supports the role of MG to mitigate bacterial-mediated inflammation (lipopolysaccharide or LPS) in vitro and CUS-induced behavior impairment in vivo to address stress-induced inflammasome-mediated innate response.

Changes in polyphenol serum levels and cognitive performance after dietary supplementation with Concord grape juice in veterans with Gulf War Illness.

AIMS: We investigated whether the consumption of Concord grape juice (CGJ) was associated with increased bioavailability of serum metabolites and their potential impact on cognitive performance in Veterans with Gulf War Illness (GWI). MAIN METHODS: Twenty-six veterans were selected from a cohort of 36 enrolled in a 24-week randomized, double-blind, Phase I/IIA clinical trial exploring whether the consumption of Concord grape juice (CGJ) was tolerable and safe in Veterans with GWI and improved cognitive function and fatigue. These 26 veterans were selected based on their completion of the entire 24-week protocol and documented adherence to the study beverage ≥80%. Differences in serum metabolite levels between CGJ and placebo at midpoint and endpoint were evaluated using two-way repeated measures ANOVA with post hoc Sidak's multiple comparison test. Bivariate correlations to assess for possible relationships between change in serum metabolite levels and change in cognitive function as measured by the Halstead Category Test-Russell Revised Version (RCAT) were also conducted. KEY FINDINGS: Seventy-six metabolites were identified and quantified in this study, with three (cyanidin-glucuronide, me-cyanidin-glucuronide, and me-malvidin-glucuronide) found to be significantly higher (p < 0.05) in the CGJ group compared to placebo at 24 weeks. Significant associations between changes in cognitive function and changes in serum levels of epicatechin-sulphate (r = 0.48, p = 0.01) and petunidin-glucuronide (r = 0.53, p < 0.01) from baseline to 24 weeks were also observed. SIGNIFICANCE: Our data suggest that dietary supplementation with CGJ is associated with increased bioavailability of specific phenolic metabolites, some of which may be correlated with cognitive performance.

Dissolution Study on Grape Polyphenol Hard Gelatin Capsule Dietary Supplements.

Methods for a dissolution study by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC-QqQ/MS) analysis of grape polyphenol dietary supplements, namely, grape seed extract (GSE) and resveratrol (RSV) capsules, were developed following the guidance of United States Pharmacopeia (USP) <2040>. Two dissolution media, 0.1 N hydrochloric acid (pH 1.2) and 0.05 M acetate buffer (pH 4.6), were evaluated with dissolution apparatus (USP 1), 100 rpm rotation speed, and 900 ml dissolution medium volume. Dissolution profiling was performed over 120 min. Major phenolic compounds of gallic acid, catechin, epicatechin, and procyanidin B2 were quantitated to obtain the dissolution profile of GSE capsules, and trans-RSV was used for RSV capsules. Results indicated that the released trans-RSV for RSV capsules in both of the dissolution media meets the USP standards, and that for the GSE capsules, all the four marker compounds passed the dissolution test in the HCl medium but did not reach a 75% release within 60 min in the acetate buffer. These promising results suggest that the general USP dissolution protocols are adequate for the successful release of RSV capsules in HCl medium and acetate buffer and GSE capsules (in HCl medium), but may be inadequate for GSE capsules in acetate buffer. These results showed that under a low pH of 1.2 (simulated stomach environment), bioactive compounds were released on time from the GSE capsules and met the USP guidelines; however, under a higher pH of 4.6 (simulated duodenum environment), the same biomarkers failed, suggesting the need to further improve the dissolution of GSE over a wider range of pH environments to enhance bioavailability and efficacy.

Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression. In this study, we characterized the neuroprotective effects of isoflavones, a class of dietary polyphenols found in soy products and in the medicinal plant red clover (Trifolium pratense). We found that isoflavone-rich extracts and individual isoflavones rescued the loss of dopaminergic neurons and the shortening of neurites in primary mesencephalic cultures exposed to two PD-related insults, the environmental toxin rotenone and an adenovirus encoding the A53T aSyn mutant. The extracts and individual isoflavones also activated the Nrf2-mediated antioxidant response in astrocytes via a mechanism involving inhibition of the ubiquitin-proteasome system, and they alleviated deficits in mitochondrial respiration. Furthermore, an isoflavone-enriched soy extract reduced motor dysfunction exhibited by rats lesioned with the PD-related neurotoxin 6-OHDA. These findings suggest that plant-derived isoflavones could serve as dietary supplements to delay PD onset in at-risk individuals and mitigate neurodegeneration in the brains of patients.

Multiple Myeloma, Hyperviscosity, Hemodialysis Filter Clogging, and Antigen Excess Artifact: A Case Report.

Kidney involvement in multiple myeloma can result in kidney failure. Unlike Waldenström macroglobulinemia, hyperviscosity syndrome is a rare occurrence in multiple myeloma. Timely detection of hyperviscosity syndrome and initiation of plasma exchange to remove paraproteins can significantly alter the clinical course and be potentially lifesaving. We report a case of hospitalized patient with kidney failure due to multiple myeloma not in remission who experienced shortened hemodialysis sessions due to early dialysis filter failure due to hyperviscosity, which was later corrected with plasmapheresis. When confirmation of high levels of serum free light chains (sFLCs) was attempted, sFLC was initially reported as "not detectable." This false-negative result reflected a laboratory artifact caused by a high abundance of sFLCs, known as antigen excess or hook phenomenon. Manual serial dilutions led to unmasking of markedly elevated κ light chain levels. This case exemplifies that patients with multiple myeloma can exhibit clinically challenging kidney manifestations even after becoming dialysis dependent.

Optimization of probiotic therapeutics using machine learning in an artificial human gastrointestinal tract.

The gut microbiota's metabolome is composed of bioactive metabolites that confer disease resilience. Probiotics' therapeutic potential hinges on their metabolome altering ability; however, characterizing probiotics' metabolic activity remains a formidable task. In order to solve this problem, an artificial model of the human gastrointestinal tract is introduced coined the ABIOME (A Bioreactor Imitation of the Microbiota Environment) and used to predict probiotic formulations' metabolic activity and hence therapeutic potential with machine learning tools. The ABIOME is a modular yet dynamic system with real-time monitoring of gastrointestinal conditions that support complex cultures representative of the human microbiota and its metabolome. The fecal-inoculated ABIOME was supplemented with a polyphenol-rich prebiotic and combinations of novel probiotics that altered the output of bioactive metabolites previously shown to invoke anti-inflammatory effects. To dissect the synergistic interactions between exogenous probiotics and the autochthonous microbiota a multivariate adaptive regression splines (MARS) model was implemented towards the development of optimized probiotic combinations with therapeutic benefits. Using this algorithm, several probiotic combinations were identified that stimulated synergistic production of bioavailable metabolites, each with a different therapeutic capacity. Based on these results, the ABIOME in combination with the MARS algorithm could be used to create probiotic formulations with specific therapeutic applications based on their signature metabolic activity.

Assessment of lemon juice quality and adulteration by ultra-high performance liquid chromatography/triple quadrupole mass spectrometry with interactive and interpretable machine learning.

A total of 81 lemon juices samples were detected using an optimized UHPLC-QqQ-MS/MS method and colorimetric assays. Concentration of 3 organic acids (ascorbic acid, malic acid and citric acid), 3 saccharides (glucose, fructose and sucrose) and 6 phenolic acids (trans-p-coumaric acid, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, caffeic acid) were quantified. Their total polyphenol, antioxidant activity and Ferric reducing antioxidant power were also measured. For the prediction of authentic and adulterated lemon juices and commercially sourced lemonade beverages based on the acquired metabolic profile, machine learning models including linear discriminant analysis, Gaussian naïve Bayes, lasso-regularized logistic regression, random forest (RF) and support vector machine were developed based on training (70%)-cross-validation-testing (30%) workflow. The predicted accuracy on the testing set is 73-86% for different models. Individual conditional expectation analysis (how predicted probabilities change when the feature magnitude changes) was applied for model interpretation, which in particular revealed the close association of RF-probability prediction with nuance characteristics of the density distribution of metabolic features. Using established models, an open-source online dashboard was constructed for convenient classification prediction and interactive visualization in real practice.

Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles.

Bioactive dietary polyphenols in grape (Vitis vinifera) have been used in Dietary Supplements (DSs) with the aim to prevent numerous diseases, including cardiovascular and neurodegenerative diseases, and to reduce depression and anxiety. Given prior recognition that DSs can be quality challenged from the purity, authentication, adulteration, and actual concentration of targeted bioactives, to ensure consumer health protection as well as the quality and safety of grape polyphenol-based DSs, the present investigation was aimed at establishing a comprehensive quality control (QC) approach for grape polyphenol-based DSs in support of a human clinical study. In this study, the manufactured grape seed polyphenol extract (GSPE) and trans-resveratrol (RSV) capsules and Concord Grape Juice (CGJ) along with the corresponding original drug materials were analyzed using the developed different liquid chromatography/UV-visible spectroscopy/mass spectrometry (LC/UV-Vis/MS) methods. The weight variation of GSPE and RSV capsules was also evaluated according to the US Pharmacopeia (USP) tests. The results indicate that the total identified polyphenol content in each grape seed extract (GSE) capsule/CGJ is very similar and all GSE/RSV capsules pass the content/weight uniformity test. Given the complexity of these and many botanical products from the issues of purity, quality, adulteration, consistency, and their coupling to the complex chemistry in each grape-derived botanical, quality assurance and the steps needed to ensure grape-derived DSs being well homogeneous and stable and containing the known and expected bioactives at specific concentration ranges are fundamental to any research study and in particular to a clinical trial. Each of these issues is essential to provide a solid foundation upon which clinical trials with botanicals can be conducted with the goal of realizing measurable mental health outcomes such as reducing depression and anxiety as well as understanding of their underlying biological mechanisms.

Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors.

Chronic stress disrupts immune homeostasis while gut microbiota-derived metabolites attenuate inflammation, thus promoting resilience to stress-induced immune and behavioral abnormalities. There are both peripheral and brain region-specific maladaptations of the immune response to chronic stress that produce interrelated mechanistic considerations required for the design of novel therapeutic strategies for prevention of stress-induced psychological impairment. This study shows that a combination of probiotics and polyphenol-rich prebiotics, a synbiotic, attenuates the chronic-stress induced inflammatory responses in the ileum and the prefrontal cortex promoting resilience to the consequent depressive- and anxiety-like behaviors in male mice. Pharmacokinetic studies revealed that this effect may be attributed to specific synbiotic-produced metabolites including 4-hydroxyphenylpropionic, 4-hydroxyphenylacetic acid and caffeic acid. Using a model of chronic unpredictable stress, behavioral abnormalities were associated to strong immune cell activation and recruitment in the ileum while inflammasome pathways were implicated in the prefrontal cortex and hippocampus. Chronic stress also upregulated the ratio of activated proinflammatory T helper 17 (Th17) to regulatory T cells (Treg) in the liver and ileum and it was predicted with ingenuity pathway analysis that the aryl hydrocarbon receptor (AHR) could be driving the synbiotic's effect on the ileum's inflammatory response to stress. Synbiotic treatment indiscriminately attenuated the stress-induced immune and behavioral aberrations in both the ileum and the brain while in a gut-immune co-culture model, the synbiotic-specific metabolites promoted anti-inflammatory activity through the AHR. Overall, this study characterizes a novel synbiotic treatment for chronic-stress induced behavioral impairments while defining a putative mechanism of gut-microbiota host interaction for modulating the peripheral and brain immune systems.

Simultaneous quantification of polyphenols, glycoalkaloids and saponins in African nightshade leaves using ultra-high performance liquid chromatography tandem mass spectrometry with acid assisted hydrolysis and multivariate analysis.

This study developed comprehensive quantification methods for major nutritive and antinutritive phytochemical aglycones in edible African nightshade leaves, an underutilized food resource in the sub-Saharan area. A simultaneous hydrolysis and extraction method was developed using methanol with 2 M sulfuric acid with incubation at 65 °C for 60 min. UHPLC-QqQ-MS/MS methods were developed and validated for hydrolysis optimization and for quantification of eight major aglycones of polyphenols, alkaloids and sapogenins in 20 differently sourced nightshade leaves, comprising two African species Solanum scabrum and S. nigrum, and from two distinct cultivation sites, one in New Jersey, US and the other in Kenya Eldoret. Variation in species, accessions and cultivation environment played an important role in affecting the phytochemical profile. Total antinutritive alkaloids and sapogenins in all nightshade leaves were evaluated and found to be safe for consumption. This work provides evidence that the consumption of African nightshade leaves as a nutrient rich leafy green vegetable is safe and can contribute to food security and nutritional improvement in the sub-Saharan area.

Pine Bark Polyphenolic Extract Attenuates Amyloid-ß and Tau Misfolding in a Model System of Alzheimer's Disease Neuropathology.

Plant-derived polyphenolic compounds possess diverse biological activities, including strong anti-oxidant, anti-inflammatory, anti-microbial, and anti-tumorigenic activities. There is a growing interest in the development of polyphenolic compounds for preventing and treating chronic and degenerative diseases, such as cardiovascular disorders, cancer, and neurological diseases including Alzheimer's disease (AD). Two neuropathological changes of AD are the appearance of neurofibrillary tangles containing tau and extracellular amyloid deposits containing amyloid-ß protein (Aß). Our laboratory and others have found that polyphenolic preparations rich in proanthocyanidins, such as grape seed extract, are capable of attenuating cognitive deterioration and reducing brain neuropathology in animal models of AD. Oligopin is a pine bark extract composed of low molecular weight proanthocyanidins oligomers (LMW-PAOs), including flavan-3-ol units such as catechin (C) and epicatechin (EC). Based on the ability of its various components to confer resilience to the onset of AD, we tested whether oligopin can specifically prevent or attenuate the progression of AD dementia preclinically. We also explored the underlying mechanism(s) through which oligopin may exert its biological activities. Oligopin inhibited oligomer formation of not only Aß1-40 and Aß1-42, but also tau in vitro. Our pharmacokinetics analysis of metabolite accumulation in vivo resulted in the identification of Me-EC-O-ß-Glucuronide, Me-(±)-C-O-ß-glucuronide, EC-O-ß-glucuronide, and (±)-C-O-ß-glucuronide in the plasma of mice. These metabolites are primarily methylated and glucuronidated C and EC conjugates. The studies conducted provide the necessary impetus to design future clinical trials with bioactive oligopin to prevent both prodromal and residual forms of AD.

A critical review on grape polyphenols for neuroprotection: Strategies to enhance bioefficacy.

The aging of populations worldwide is driving greater demands for dietary polyphenols which have been recognized as promising prophylactic and/or therapeutic agents in the context of neurodegeneration, and are ubiquitously present in plant-based diets. In particular, grape-derived products encompass a wide array of phenolic compounds purported with multiple health benefits including neuroprotective efficacy. Despite the increasing preclinical and clinical evidence demonstrating high potential of grape polyphenol (GPP)-rich botanicals in preventing and attenuating diverse neurodegenerative disorders, the limited bioavailability of GPPs, especially in the brain, generates questions as to their applications and effectiveness in neuroprotection. To address this issue, significant research efforts have been made to enhance oral bioavailability of GPPs via application of novel strategies. This review highlights some critical issues related to the bioavailability and neuroprotective efficacy of GPPs and GPP-rich botanicals. The representative bioavailability-enhancing strategies are critically reviewed to provide practical solutions for augmenting the bioefficacy of GPP-rich botanicals. Synergistic applications of encapsulation techniques (for physiochemical protection and bypassing xenobiotic metabolism) and dietary intervention strategies involving modulation of gut microbiota (for generating more bioavailable phenolic metabolites) appear promising, and may substantially enhance the bioefficacy, especially the neuroprotective efficacy, of orally consumed GPPs.

Quantity assessment of polyphenols, glycoalkaloids and saponins in Solanum scabrum berries of different genetic sources and maturity by HPLC/UV-visible/MS methods.

BACKGROUND: Solanum scabrum berries in sub-Saharan Africa are prolific but neglected as an agricultural resource. Recognition and application of such underutilized resources rely on systematic study of the relevant phytochemicals of commercial value. RESULTS: The quantities of a total of 54 phytochemicals in Solanum scabrum berries were assessed using HPLC-MS methods. Berries from eight different genetic sources were analyzed with two entries monitored across different maturation stages. There was a significant variation among mature berries in the accumulation of phenolic acids, 91.5-794 mg·100 g-1 dry weight (DW); flavonols, 76.3-897 mg·100 g-1 DW; anthocyanins, 178-4650 mg·100 g-1 DW; glycoalkaloids, 1.76-1630 mg·100 g-1 DW; and saponins, 82.2-606 mg·100 g-1 DW. Fruit development from immature to post-frost harvest featured dynamic changes in phytochemical composition and, despite remarkable differences in the absolute magnitude of content, the trend of change was generally similar in different genetic sources. CONCLUSIONS: The genotype-dependent difference in toxic glycoalkaloids in mature berries may partially explain the consumption controversy as it reflects glycoalkaloid content. The analytical methods applied in this work should serve for quality control of glycoalkaloids thereby improving the safe utilization of this berry. In addition, the selection and breeding of new genotypes with low and safe levels of glycoalkaloids and saponins in the berry could be of value in sub-Saharan Africa to increase nutrition and generate new income opportunities for growers. © 2019 Society of Chemical Industry.

Identification of Polyphenols, Glycoalkaloids, and Saponins in Solanum scabrum Berries Using HPLC-UV/Vis-MS.

Consumption safety of Solanum scabrum berries is controversial in different cultural practices and evaluation of the toxicity as well as micronutrition value relies on relevant phytochemical study. Thus, this study aimed to systematically profile the phytochemicals in the berries from different genetic sources and maturity. Using a combination of three different and complementary methods of HPLC-UV/Vis-MS or MS/MS with acid-assisted hydrolysis, a total of 54 phytochemicals were identified including polyphenols, saponins and toxic glycoalkaloids. Particularly, a broad range of glycoalkaloids of solasodine and its uncommon or potentially novel hydroxylated and methylated derivatives were reported, with the structure putatively identified based on the known scaffold-fragmentation pattern. Other identified phytochemicals included phenolic acids of chlorogenic acid and neochlorogenic acid, flavonol glycosides of quercetin and isorhamnetin, anthocyanins of petunidin, malvidin and delphinidin, and saponins of diosgenin and tigogenin. PRACTICAL APPLICATION: This study provides solutions for identifying the phytochemicals of S. scabrum berries, and unveiled for the first time a wide range of toxic glycoalkaloids of solasodine and analogues in the berries from different genetic sources and maturation stages. This work laid the foundation for prospective quantitative determination of berry phytochemicals and future toxicity and nutrition evaluation, and could also apply to facilitate screening or breeding for glycoalkaloid-deficient genotypes that can be used as new food supply.