Daily olive oil intake is feasible to reduce trigeminal neuralgia facial pain: A pilot study.

Extra virgin olive oil (EVOO) is thought to contribute to neuroprotection and, thus, may influence pain symptoms experienced by adults with demyelination-related trigeminal neuralgia (TN). This study aimed to determine the feasibility of daily intake of EVOO and its potential to alleviate facial pain of TN. Adults, self-reporting as female and affected by TN, were enrolled in a 16-week nonblinded, parallel study. After a 4-week baseline, participants were randomized to 60 mL/day EVOO or control (usual diet and no supplemental EVOO) for 12 weeks. Participants completed a daily questionnaire on pain intensity and compliance, the Penn Facial Pain Scale weekly, the 36-Item Short Form Survey monthly, and dietary assessment during baseline and intervention. Participants (n = 52; 53.3 ± 12.9 years) were recruited nationally; 42 completed the study. The EVOO group, with 90% intake compliance, showed significant decreases in the Penn Facial Pain Scale items of interference with general function, interference with orofacial function, and severity of pain from baseline, whereas the control group showed no improvements. EVOO benefit, compared with control, trended for the interference with orofacial function (P = .05). The 36-Item Short Form Survey items of role limitations resulting from emotional problems and role limitations from physical health favored EVOO. The EVOO group significantly improved their Healthy Eating Index 2015 component scores of fatty acids (primarily from increased oleic acid), sodium, and refined grains. EVOO intake of 60 mL/day was feasible for participants experiencing TN and may mitigate pain and improve quality of life. This trial was registered at clinicaltrials.gov (NCT05032573).

Cranberry extract initiates intrinsic apoptosis in HL-60 cells by increasing BAD activity through inhibition of AKT phosphorylation.

BACKGROUND: Cranberry has been studied as a potential anticancer agent as it is capable of inducing apoptosis within cancer cells. The aim of this study was to better define the mechanism by which cranberry triggers apoptosis in HL-60 cells. METHODS: The study was carried on cranberry extracts (CB). Anti-apoptotic B-cell lymphoma-2 (BCL-2) and pro-apoptotic BCL-2-associated death promoter death (BAD) proteins in cell lysates were detected through Western blotting techniques. Equivalent protein loading was confirmed through anti-α-tubulin antibody. RESULTS: The results showed that treatment of HL-60 cells with CB causes a significant increase in the levels of caspase-9 and caspases-3/7 and increased mitochondrial outer membrane permeability, leading to the release of cytochrome C and Smac. These apoptotic events were associated with a significant decrease in protein kinase B (AKT) phosphorylation, which caused significant increase in BAD de-phosphorylation and promoted a sequence of events that led to intrinsic apoptosis. CONCLUSION: The study findings have described a molecular framework for CB-initiated apoptosis in HL-60 cells and suggested a direction for future in vivo studies investigating the anticancer effect of cranberry.

Immunomodulatory Effects of Glutathione, Garlic Derivatives, and Hydrogen Sulfide.

Glutathione and aged garlic extract are sulfur-containing products that play important protective and regulatory roles within the immune system and in oxidative processes. Hydrogen sulfide (H2S), an endogenous, gaseous, signaling transmitter, has also been shown to be involved in the regulation of inflammation. Recent studies have shown that sulfur-containing compounds from garlic have beneficial effects in attenuating outcomes associated with cardiovascular disease and inflammation by a mechanism that may be related to the H2S signaling pathway. In this review, we summarize the main functions of glutathione (GSH), garlic derivatives and H2S and their role in the immune response and impact on health and disease.

Beyond Academics: A Model for Simultaneously Advancing Campus-Based Supports for Learning Disabilities, STEM Students' Skills for Self-Regulation, and Mentors' Knowledge for Co-regulating and Guiding.

Learning disabilities are highly prevalent on college campuses, yet students with learning disabilities graduate at lower rates than those without disabilities. Academic and psychosocial supports are essential for overcoming challenges and for improving postsecondary educational opportunities for students with learning disabilities. A holistic, multi-level model of campus-based supports was established to facilitate culture and practice changes at the institutional level, while concurrently bolstering mentors' abilities to provide learning disability-knowledgeable support, and simultaneously creating opportunities for students' personal and interpersonal development. Mixed methods were used to investigate implementation of coordinated personal, interpersonal, and institutional level supports for undergraduate science, technology, engineering, and math (STEM) students with learning disabilities. A one-group pre-test post-test strategy was used to examine undergraduate outcomes. Participants included 52 STEM undergraduates with learning disabilities, 57 STEM graduate student mentors, 34 STEM faculty mentors, and 34 university administrators and personnel as members of a university-wide council. Enrolled for 2 years, undergraduates were engaged in group meetings involving psychoeducation and reflective discussions, development of self-advocacy projects, and individual mentorship. Undergraduates reported improved self-efficacy (p = 0.001), campus connection (p < 0.001), professional development (p ≤ 0.002), and self-advocacy (p < 0.001) after two academic years. Graduate student mentors increased their understanding about learning disabilities and used their understanding to support both their mentees and other students they worked with. Council members identified and created opportunities for delivering learning disability-related trainings to faculty, mentors and advisors on campus, and for enhancing coordination of student services related to learning and related disorders. Disability-focused activities became integrated in broader campus activities regarding diversity. This research explicates a role that college campuses can play in fostering the wellbeing and the academic and career development of its students with developmental learning and related disorders. It offers an empirically tested campus-based model that is multilevel, holistic, and strengths-based for supporting positive outcomes of young people with learning disabilities in STEM. Moreover, findings advance the knowledge of supports and skills that are important for self-regulating and navigating complex and multi-faceted disability-related challenges within both the postsecondary educational environment and the young adults' sociocultural context.

Aged garlic extract supplementation modifies inflammation and immunity of adults with obesity: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Obesity is a serious global health issue and often results in low-grade systemic inflammation, increasing the risk for several chronic diseases. If obesity-induced inflammation could be reduced, fewer complications and co-morbidities might occur. OBJECTIVE: To investigate whether daily supplementation with aged garlic extract (AGE) could reduce chronic inflammation and improve immune function in adults with obesity. METHODS: Fifty-one healthy adults with obesity (mean age 45.6 ± 1.6 years, mean BMI 36.1 ± 0.9 kg/m2) were recruited to participate in a parallel, double-blind, placebo-controlled, randomized study. After being matched by BMI, participants were randomized into the AGE supplementation or placebo group. Participants were asked to take a divided daily dose of 3.6 g AGE or placebo, with food for 6 weeks. Blood lipid and inflammatory markers were assessed at baseline and after 6 weeks of supplementation. Additionally, peripheral blood mononuclear cells (PBMC) were isolated from whole blood and used to detect changes in immune cell populations and levels of cytokine secretion. A one-way ANCOVA was performed to evaluate differences between the two groups, controlling for respective baseline values. RESULTS: At the end of study, serum IL-6 (p = 0.04) and TNF-α (p = 0.05) of participants consuming AGE were significantly lower than those consuming the placebo capsules. PBMC flow cytometry results showed that participants from the AGE group had a higher proportion of γδ-T cells (p = 0.03) and a lower proportion of NKT cells (p = 0.02) in the total population of lymphocytes. There was no difference in percentage of NK cells between the two groups. A significant difference in blood LDL concentration was also observed (p = 0.05). Total cholesterol and non-HDL cholesterol tended to differ between participants from the AGE group and those from the placebo group, although values did not achieve statistical significance. CONCLUSION: Six weeks of AGE consumption modulated immune cell distribution, prevented the increase of serum TNF-α and IL-6 concentrations and reduced blood LDL concentration in adults with obesity. AGE, taken consistently, may be beneficial in preventing the development of chronic diseases associated with low-grade inflammation in adults with obesity. Registered under ClinicalTrials.gov with the identifier code NCT01959646.

Aged Garlic Extract Modifies Human Immunity.

Garlic contains numerous compounds that have the potential to influence immunity. Immune cells, especially innate immune cells, are responsible for the inflammation necessary to kill pathogens. Two innate lymphocytes, γδ-T and natural killer (NK) cells, appear to be susceptible to diet modification. The purpose of this review was to summarize the influence of aged garlic extract (AGE) on the immune system. The author's laboratory is interested in AGE's effects on cell proliferation and activation and inflammation and to learn whether those changes might affect the occurrence and severity of colds and flu. Healthy human participants (n = 120), between 21 and 50 y of age, were recruited for a randomized, double-blind, placebo-controlled parallel-intervention study to consume 2.56 g AGE/d or placebo supplements for 90 d during the cold and flu season. Peripheral blood mononuclear cells were isolated before and after consumption, and γδ-T and NK cell function was assessed by flow cytometry. The effect on cold and flu symptoms was determined by using daily diary records of self-reported illnesses. After 45 d of AGE consumption, γδ-T and NK cells proliferated better and were more activated than cells from the placebo group. After 90 d, although the number of illnesses was not significantly different, the AGE group showed reduced cold and flu severity, with a reduction in the number of symptoms, the number of days participants functioned suboptimally, and the number of work/school days missed. These results suggest that AGE supplementation may enhance immune cell function and may be partly responsible for the reduced severity of colds and flu reported. The results also suggest that the immune system functions well with AGE supplementation, perhaps with less accompanying inflammation. This trial was registered at clinicaltrials.gov as NCT01390116.

Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy Leukemia Cell Line.

BACKGROUND: Red-fleshed sweet orange juice (ROJ) comes from a new variety of citrus cultivated in Brazil that contains high levels of ß-carotene and lycopene, and similar amounts of hesperidin (HSP) and nutrients, equivalently to blond orange juice (BOJ). Such bioactive compounds are associated with chemopreventive actions in several cancer cell lines. The purpose of this study was to examine the cytotoxicity, cell cycle, apoptosis, and cytokine secretion after BOJ, ROJ, and HSP treatment of a novel T acute lymphoblastic leukemia cell line, Loucy. MATERIALS AND METHODS: Loucy cells were incubated for 24-h with BOJ, ROJ, and HSP, and the viability was measured using trypan blue. Cell cycling and apoptosis were assessed by propidium iodide (PI) and annexin V-FITC/PI flow cytometry, respectively. Secretion of cytokines IL-1α, IL1-ß, IL-2, IL-4, IL-6, IL-10, IL-17A, IFNγ, TNFα, TGFß, MIPα, and MIPß was determined by ELISA array. RESULTS: BOJ and ROJ treatments promoted Loucy cell cytotoxicity. Additionally, BOJ induced cell cycle arrest in the G0/G1 phase, and decreased the cell accumulation in the G2/M. ROJ decreased only the G0/G1 fraction, while HSP did not change the cell cycle. BOJ led to apoptosis in a different fashion of ROJ, while the first treatment induced apoptosis by increase of late apoptosis and primary necrotic fractions, the second increased early and late apoptosis, and primary necrotic fraction compared to positive controls. HSP had no effect on apoptosis. IL-6 and IL-10 were abrogated by all treatments. CONCLUSIONS: Taking together, these results suggest potential chemopreventive effects of BOJ and ROJ on Loucy cells.

Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

OBJECTIVE: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community. METHODS: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing. RESULTS: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo. CONCLUSIONS: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults.

BACKGROUND: Mushrooms are widely cited for their medicinal qualities, yet very few human intervention studies have been done using contemporary guidelines. OBJECTIVE: The aim of this study was to determine whether consumption of whole, dried Lentinula edodes (shiitake) mushrooms could improve human immune function. Primary objectives were to ascertain whether L. edodes consumption would improve γδ-T cell proliferation and activation responses, quantify a dose response, and elicit cytokine secretion patterns. Secondary objectives included determining changes in natural killer T (NK-T) cell proliferation and activation, secretory immunoglobulin A (sIgA) in saliva, and C-reactive protein (CRP) in serum. DESIGN: Fifty-two healthy males and females, aged 21-41 years, participated in a 4-week parallel group study, consuming either 5 or 10 g of mushrooms daily. Each subject had blood drawn before and after 4 weeks of daily L. edodes consumption. Saliva and serum were also collected. Peripheral blood mononuclear cells were cultured in autologous serum for 24 hours or 6 days, stained, and examined by flow cytometry. RESULTS: Eating L. edodes for 4 weeks resulted in increased ex vivo proliferation of γδ-T (60% more, p < 0.0001) and NK-T (2-fold more, p < 0.0001) cells. Both cell types also demonstrated a greater ability to express activation receptors, suggesting that consuming mushrooms improved cell effector function. The increase in sIgA implied improved gut immunity. The reduction in CRP suggested lower inflammation. The pattern of cytokines secreted before and after mushroom consumption was significantly different; consumption resulted in increased interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and IL-1α levels, a decreased macrophage inflammatory protein-1α/chemokine C-C ligand 3 (MIP-1α/CCL3) level, and no change to IL-6, IL-1ß, MIP-1ß, IL-17 and interferon (IFN)-γ levels. CONCLUSIONS: Regular L. edodes consumption resulted in improved immunity, as seen by improved cell proliferation and activation and increased sIgA production. The changes observed in cytokine and serum CRP levels suggest that these improvements occurred under conditions that were less inflammatory than those that existed before consumption.

Mushrooms and Health Summit proceedings.

The Mushroom Council convened the Mushrooms and Health Summit in Washington, DC, on 9-10 September 2013. The proceedings are synthesized in this article. Although mushrooms have long been regarded as health-promoting foods, research specific to their role in a healthful diet and in health promotion has advanced in the past decade. The earliest mushroom cultivation was documented in China, which remains among the top global mushroom producers, along with the United States, Italy, The Netherlands, and Poland. Although considered a vegetable in dietary advice, mushrooms are fungi, set apart by vitamin B-12 in very low quantity but in the same form found in meat, ergosterol converted with UV light to vitamin D2, and conjugated linoleic acid. Mushrooms are a rare source of ergothioneine as well as selenium, fiber, and several other vitamins and minerals. Some preclinical and clinical studies suggest impacts of mushrooms on cognition, weight management, oral health, and cancer risk. Preliminary evidence suggests that mushrooms may support healthy immune and inflammatory responses through interaction with the gut microbiota, enhancing development of adaptive immunity, and improved immune cell functionality. In addition to imparting direct nutritional and health benefits, analysis of U.S. food intake survey data reveals that mushrooms are associated with higher dietary quality. Also, early sensory research suggests that mushrooms blended with meats and lower sodium dishes are well liked and may help to reduce intakes of red meat and salt without compromising taste. As research progresses on the specific health effects of mushrooms, there is a need for effective communication efforts to leverage mushrooms to improve overall dietary quality.

Consumption of cranberry polyphenols enhances human γδ-T cell proliferation and reduces the number of symptoms associated with colds and influenza: a randomized, placebo-controlled intervention study.

BACKGROUND: Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity, specifically γδ-T cell proliferation, after daily consumption of a cranberry beverage, and its effect on health outcomes related to cold and influenza symptoms. METHODS: The study was a randomized, double-blind, placebo-controlled, parallel intervention. Subjects drank a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n = 22) or a placebo beverage (n = 23), daily, for 10 wk. PBMC were cultured for six days with autologous serum and PHA-L stimulation. Cold and influenza symptoms were self-reported. RESULTS: The proliferation index of γδ-T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption (p <0.001). In the cranberry beverage group, the incidence of illness was not reduced, however significantly fewer symptoms of illness were reported (p = 0.031). CONCLUSIONS: Consumption of the cranberry beverage modified the ex vivo proliferation of γδ-T cells. As these cells are located in the epithelium and serve as a first line of defense, improving their function may be related to reducing the number of symptoms associated with a cold and flu.

Hyaluronic Acid (HA) Viscosupplementation on Synovial Fluid Inflammation in Knee Osteoarthritis: A Pilot Study.

OBJECTIVE: This study examined the changes in synovial fluid levels of cytokines, oxidative stress and viscosity six months after intraarticular hyaluronic acid (HA) treatment in adults and elderly adults with knee osteoarthritis (OA). DESIGN: This was a prospective, repeated-measures study design in which patients with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were stratified by age (adults, 50-64 years and elderly adults, ≥65 years). Ambulatory knee pain values and self-reported physical activity were collected at baseline and month six. MATERIALS AND METHODS: Knee synovial fluid aspirates were collected at baseline and at six months. Fluid samples were analyzed for pro-inflammatory cytokines (interleukins 1ß, 6,8,12, tumor necrosis factor-α, monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10 13), oxidative stress (4-hydroxynonenal) and viscosity at two different physiological shear speeds 2.5Hz and 5Hz. RESULTS: HA improved ambulatory knee pain in adults and elderly groups by month six, but adults reported less knee pain-related interference with participation in exercise than elderly adults. A greater reduction in TNF-α occurred in adults compared to elderly adults (-95.8% ± 7.1% vs 19.2% ± 83.8%, respectively; p=.044). Fluid tended to improve at both shear speeds in adults compared to the elderly adults. The reduction in pain severity correlated with the change in IL-1ß levels by month six (r= -.566; p=.044). CONCLUSION: Reduction of knee pain might be due to improvements in synovial fluid viscosity and inflammation. Cartilage preservation may be dependent on how cytokine, oxidative stress profiles and viscosity change over time.

Metabolite profile analysis reveals functional effects of 28-day vitamin B-6 restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy men and women.

Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate (PLP) concentration, is associated with increased risk of vascular disease. PLP plays many roles, including in one-carbon metabolism for the acquisition and transfer of carbon units and in the transsulfuration pathway. PLP also serves as a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of these metabolites can provide information reflecting the functional impact of marginal vitamin B-6 deficiency. We report here the concentration of major constituents of one-carbon metabolic processes and the tryptophan catabolic pathway in plasma from 23 healthy men and women before and after a 28-d controlled dietary vitamin B-6 restriction (<0.35 mg/d). liquid chromatography-tandem mass spectrometry analysis of the compounds relevant to one-carbon metabolism showed that vitamin B-6 restriction yielded increased cystathionine (53% pre- and 76% postprandial; P < 0.0001) and serine (12% preprandial; P < 0.05), and lower creatine (40% pre- and postprandial; P < 0.0001), creatinine (9% postprandial; P < 0.05), and dimethylglycine (16% postprandial; P < 0.05) relative to the vitamin B-6-adequate state. In the tryptophan pathway, vitamin B-6 restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P < 0.01) and higher 3-hydroxykynurenine (39% pre- and 34% postprandial; P < 0.01). Multivariate ANOVA analysis showed a significant global effect of vitamin B-6 restriction and multilevel partial least squares-discriminant analysis supported this conclusion. Thus, plasma concentrations of creatine, cystathionine, kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6 restriction on the profiles of one-carbon and tryptophan metabolites and serve as biomarkers of functional effects of marginal vitamin B-6 deficiency.

Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease.

Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of ß-amyloid (Aß) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on Aß generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of Aß(1-40) and Aß(1-42) that is necessary for the formation of neurotoxic oligomeric Aß species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.

Preparation, characterization, and induction of cell apoptosis of cocoa procyanidins-gelatin-chitosan nanoparticles.

Cocoa procyanidins (CPs)-gelatin-chitosan nanoparticles were fabricated based on the procyanidin-protein and electrostatic interactions, with an objective to enhance the stability and bioactivity of CPs. The CPs were purified using chromatographic methods and analyzed using HPLC equipped with a fluorescence detector (FLD) and mass spectrometer (MS). The purified CPs had a purity of 53.1% (w/w) and contained procyanidin oligomers (from monomer to decamers) and polymers, with polymers being the predominant component (26.4%, w/w). Different CPs-gelatin-chitosan mass ratios were tested to investigate the effects of formulation on the nanoparticle fabrication. Using CPs-gelatin-chitosan mass ratio of 0.75:1:0.5, the resultant nanoparticles had a particle size of 344.7 nm, zeta-potential of +29.8 mV, particle yield of 51.4%, loading efficiency of 50.1%, and loading capacity of 20.5%. The CPs-gelatin-chitosan nanoparticles were spherical as observed by scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) suggested that the primary interaction between the CPs and gelatin was hydrogen bond and hydrophobic interaction, while electrostatic interaction was the main binding force between chitosan and CPs-gelatin nanoparticles. Nanoencapsulation of the CPs significantly improved the stability of the CPs at 60°C. The CPs-gelatin-chitosan nanoparticles showed the same apoptotic effects at lower concentrations in human acute monocytic leukemia THP-1 cells compared with the CPs in solution.

Transport of cranberry A-type procyanidin dimers, trimers, and tetramers across monolayers of human intestinal epithelial Caco-2 cells.

A-type procyanidin oligomers in cranberries are known to inhibit the adhesion of uropathogenic bacteria. B-type procyanidin dimers and trimers are absorbed by humans. The absorption of A-type procyanidins from cranberries in humans has not been demonstrated. This study examined the transport of A-type cranberry procyanidin dimers, trimers, and tetramers on differentiated human intestinal epithelial Caco-2 cell monolayers. Procyanidins were extracted from cranberries and purified using chromatographic methods. Fraction I contained predominantly A-type procyanidin dimer A2 [epicatechin-(2-O-7, 4-8)-epicatechin]. Fraction II contained primarily A-type trimers and tetramers, with B-type trimers, A-type pentamers, and A-type hexamers being minor components. Fraction I or II in solution was added onto the apical side of the Caco-2 cell membranes. The media at the basolateral side of the membranes were analyzed using HPLC-MS(n) after 2 h. Data indicated that procyanidin dimer A2 in fraction I and A-type trimers and tetramers in fraction II traversed across Caco-2 cell monolayers with transport ratio of 0.6%, 0.4%, and 0.2%, respectively. This study demonstrated that A-type dimers, trimers, and tetramers were transported across Caco-2 cells at low rates, suggesting that they could be absorbed by humans after cranberry consumption.

Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention.

BACKGROUND & AIMS: Earlier studies show that dietary bioactive compounds can modify proliferation of γδ-T cells. Garlic contains numerous compounds that have this potential and, in addition, has been shown to influence NK cell function. Our primary aim was to demonstrate that aged garlic extract could modify these immune cells. METHODS: A randomized, double-blind, placebo-controlled parallel intervention study recruited 120 healthy subjects (60 per group) to determine the effect of aged garlic extract supplementation (2.56 g/d) on immune cell proliferation and cold and flu symptoms. RESULTS: After 45 d of consuming an encapsulated aged garlic extract, γδ-T cells (p = 0.039, n = 56) and NK cells (p = 0.043, n = 56) were shown to proliferate better compared to placebo. After 90 d of supplementation, illness diary entries showed that the incidence of colds and flu, a secondary outcome, were not statistically different; however, the group consuming the aged garlic extract appeared to have reduced severity as noted by a reduction in the number of symptoms reported (21% fewer, p < 0.001, z-test of proportions), a reduction in the number of days (61% fewer, p < 0.001, z-test) and incidences (58% fewer p < 0.001, z-test) where the subjects functioned sub-optimally and the number of work/school days missed due to illness (58% fewer, p = 0.035, z-test). CONCLUSIONS: These results suggest that supplementation of the diet with aged garlic extract may enhance immune cell function and that this may be responsible, in part, for reduced severity of colds and flu.

Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks.

OBJECTIVE: The aim of this work was to determine the bioavailability of herbs and spices after human consumption by measuring the ability to protect lymphocytes from an oxidative injury and by examining the impact on inflammatory biomarkers in activated THP-1 cells. METHODS: Ten to 12 subjects in each of 13 groups consumed a defined amount of herb or spice for 7 days. Blood was drawn from subjects before consumption and 1 hour after taking the final herb or spice capsules. Subject serum and various extractions of the herbs and spices were analyzed for antioxidant capacity by oxygen radical absorbance capacity (ORAC) analysis or by 1,1-diphenyl-2-picrylhydrzyl (DPPH). Subject peripheral blood mononuclear cells (PBMCs) in medium with10% autologous serum were incubated with hydrogen peroxide to induce DNA strand breaks. Subject serum was also used to treat activated THP-1 cells to determine relative quantities of 3 inflammatory cytokine (tumor necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and IL-6) mRNAs. RESULTS: Herbs and spices that protected PBMCs against DNA strand breaks were paprika, rosemary, ginger, heat-treated turmeric, sage, and cumin. Paprika also appeared to protect cells from normal apoptotic processes. Of the 3 cytokine mRNAs studied (TNF-α, IL-1α, and IL-6), TNF-α was the most sensitive responder to oxidized LDL-treated macrophages. Clove, ginger, rosemary, and turmeric were able to significantly reduce oxidized LDL-induced expression of TNF-α. Serum from those consuming ginger reduced all three inflammatory biomarkers. Ginger, rosemary, and turmeric showed protective capacity by both oxidative protection and inflammation measures. CONCLUSIONS: DNA strand breaks and inflammatory biomarkers are a good functional measure of a food's bioavailability.

Fabrication of nanoparticles using partially purified pomegranate ellagitannins and gelatin and their apoptotic effects.

SCOPE: Nanoparticles possess unique chemical and biological properties compared to bulk materials. Bioactive food components encapsulated in nanoparticles may have increased bioavailability and bioactivities. METHODS AND RESULTS: Self-assembled nanoparticles made of partially purified pomegranate ellagitannins (PPE) and gelatin were fabricated using three PPE-to-gelatin mass ratios (1:5, 5:5, and 7:5). The PPE contained 16.6% (w/w) of punicalagin A, 32.5% (w/w) of punicalagin B, and a small amount of ellagic acid-hexoside and ellagic acid (1%, w/w). Nanoparticles fabricated using the ratio 5:5 had a particle size of 149.3±1.8 nm, positive zeta-potential of 17.8±0.9 mV, production efficiency 53.0±4.2%, and spherical morphology under scanning electron microscopy. Loading efficiency of punicalagin A and punicalagin B in these particles were 94.2±0.4% and 83.8±0.5 %, respectively. Loading capacity was 14.8±1.5% and 25.7±2.2%, respectively. Only punicalagin anomers were able to bind with gelatin to form nanoparticles, whereas ellagic acid-hexoside or ellagic acid could not. Fourier transform infrared spectroscopy suggested that the interactions between ellagitannins and gelatin were hydrogen bonding and hydrophobic interactions. PPE-gelatin nanoparticle suspension was less effective than PPE in inducing the early stage of apoptosis on human promyelocytic leukemia cells HL-60. But they had similar effects in inducing late stage of apoptosis and necrosis. CONCLUSION: Pomegranate ellagitannins bind with gelatin to form self-assembled nanoparticles. Ellagitannins encapsulated in nanoparticles had decreased apoptotic effects on leukemia cells HL-60.

Regular consumption of concord grape juice benefits human immunity.

γδ T cells are important immune surveillance cells residing in epithelial layers lining the intestine, lung, and reproductive tract. The main objective of this study was to test the hypothesis that consumption of dietary compounds from grapes would modify γδ T-cell function. Other factors related to immune function after grape juice consumption were also tested. A randomized, double-blind, placebo-controlled, parallel intervention was conducted: 100% grape juice made from Concord grapes or a placebo beverage was consumed by 85 individuals daily for 9 weeks. Subjects were asked not to consume other red, blue, and purple fruits during the study. Blood samples, taken at the beginning and the end, were analyzed for γδ T-cell numbers and proliferation, vitamin C, antioxidant capacity, and the ability to protect DNA from strand breaks. Those consuming the grape juice had significantly greater numbers of circulating γδ T cells and higher serum vitamin C levels compared to the placebo by two-way repeated-measure analysis of variance (P < .05). Individuals consuming the placebo had lower serum antioxidant activity, less γδ T-cell proliferation, and increased DNA strand breaks when challenged with H(2)O(2). Analysis of the data by structural equation modeling confirmed that 61% of the variance in biological functions at 9 weeks was due to grape juice consumption. Based on conventional statistical analyses, as well as on sophisticated modeling techniques, regular consumption of purple grape juice in the absence of other red, blue, or purple fruits benefited immunity in healthy, middle-aged human subjects.