A Randomized, Double-Blind, Placebo-Controlled Study of an Anthocyanin-Rich Functional Ingredient on Cognitive Function and Eye Dryness in Late Adulthood Volunteers: Roles of Epigenetic and Gut Microbiome Modulations.

Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.

Effects of Irvingia gabonensis Extract on Metabolism, Antioxidants, Adipocytokines, Telomere Length, and Aerobic Capacity in Overweight/Obese Individuals.

We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p < 0.01) and 12 weeks (p < 0.05) and serum adiponectin after 3 weeks (p < 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.

Vitamin C supplementation improves blood pressure and oxidative stress after acute exercise in patients with poorly controlled type 2 diabetes mellitus: A randomized, placebo-controlled, cross-over study.

This study aimed to assess the effect of Vitamin C on blood pressure (BP), and subsequently on oxidative stress and nitric oxide (NO) release, following the low-intensity exercise in the patients. This study included 24 patients with type 2 diabetes mellitus (T2D) (age, 53 ± 7 years; hemoglobin A1c, 10.1% ± 0.9%) randomized into two 6-week daily arms based on the consumption of either placebo or 1000 mg Vitamin C. The crossover trial occurred after a 6-week washout. Before and after both supplementation arms, all patients performed cycling exercise at 33% of peak oxygen consumption for 20 min. BP was measured before, immediately, and 60 min after the exercise. Blood samples were drawn immediately before and after the exercise to determine plasma ascorbate, malondialdehyde (MDA), F2-isoprostanes (F2-IsoPs), and NO concentrations. Data showed significant lower BP in the Vitamin C arm when compared with the placebo arm (systolic BP [SBP] P < 0.001 at every time point, diastolic BP [DBP] P < 0.001 except at immediately after exercise, P < 0.05). Plasma ascorbate concentration (P < 0.05 at every time point) and plasma NO (at resting P < 0.001, immediately after exercise P < 0.05) were significantly increased in the Vitamin C arm than in the placebo arm. Plasma MDA (P < 0.05 at every time point) and F2-IsoPs (P < 0.05 at every time point) concentrations were significantly lower in the Vitamin C arm than in the placebo arm. In addition, data showed significantly lower SBP (P < 0.001 at every time point), DBP (P < 0.001 except at immediately after exercise P < 0.05), plasma MDA (P < 0.001 at every time point), and F2-IsoPs (P < 0.05 at every time point) at post-supplementation than at pre-supplementation. Besides, there were significantly higher plasma ascorbate (P < 0.05 at every time point) and NO (at rest P < 0.01, immediately after exercise P < 0.05) concentrations at post-supplementation than at pre-supplementation. This is in contrast to the placebo treatment arm which demonstrated no statistical difference in all outcomes throughout the experiment. This study suggests that 6-week Vitamin C supplementation decreased preexercise and postexercise BPs, possibly due to improved oxidative stress and NO release. However, exercise had no effect on any outcome measures.

Tangeretin ameliorates erectile and testicular dysfunction in a rat model of hypertension.

Tangeretin is a polymethoxyflavone concentrated in citrus peels and has several biological activities. This study examined whether tangeretin improved reproductive dysfunction in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats received L-NAME to induce hypertension and reproductive dysfunction for 5 w and were treated with tangeretin (15 or 30 mg/kg) or sildenafil citrate (10 mg/kg) for the final two weeks. Mean arterial pressure (MAP), intracavernosal pressure (ICP) response to cavernous nerve stimulation, endothelial nitric oxide synthase (eNOS), Angiotensin II receptor type 1 (AT1R) and gp91phox protein expressions and malondialdehyde (MDA) level in penile tissues were measured. Sperm concentrations and motility, seminiferous tubule morphology, serum testosterone, testicular eNOS and steroidogenic acute regulatory protein (StAR) expression were evaluated. Aortic superoxide generation, plasma and testicular MDA and plasma nitrate/nitrite levels were determined. Tangeretin reduced blood pressure and increased the maximum ICP/MAP associated with suppression of AT1R/gp91phox and upregulation of eNOS expression in hypertensive rats (P < 0.05). Furthermore, improvement of sperm quality relevant to increased testicular eNOS and StAR expression was found in tangeretin treated rats (P < 0.05). Changes in seminiferous tubule morphology in hypertensive rats were recovered by tangeretin (P < 0.05). It increased testosterone levels and reduced oxidative stress biomarkers and raised plasma nitrate/nitrite levels in L-NAME rats (P < 0.05). In conclusion, tangeretin improved maximum ICP/MAP and testicular dysfunction and morphology in rats treated with L-NAME. The molecular mechanisms are mediated by modulations of penile eNOS and AT1R/gp91phox expressions and testicular eNOS and StAR expression.

Cerebroprotective Effect against Cerebral Ischemia of the Combined Extract of Oryza sativa and Anethum graveolens in Metabolic Syndrome Rats.

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract of Oryza sativa and Anethum graveolens, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract of Oryza sativa L. and Anethum graveolens Linn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions of proinflammatory cytokines (NF-κB, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

Cashew apple juice supplementation enhances leukocyte count by reducing oxidative stress after high-intensity exercise in trained and untrained men.

BACKGROUND: Cashew apple juice (CAJ) was shown to improve immunological mechanisms by regulating a balance between reactive oxygen species and antioxidant concentrations. However, no study exploring the effects of the CAJ and training status on the immune system and oxidative stress induced by exercise. Therefore, we investigated the effects of CAJ supplementation primarily on leukocyte counts and secondary on oxidative stress and cortisol changes after high-intensity exercise in trained and untrained men. METHODS: Ten moderately (endurance) trained (Age = 21.5 ± 0.97 yr., VO2max = 45.6 ± 4.12 mL/kgBM/min) and ten sedentary men (Age = 20.4 ± 2.72 yr., VO2peak = 32.2 ± 7.26 mL/kgBM/min) were randomized to ingest either daily CAJ or a placebo at 3.5 mL/kgBM/day for 4 weeks, with a four-week washout period. Before and after each period, they performed 20-min, high-intensity cycling (85% VO2max), with blood samples collected immediately preceding and the following exercise. Samples were analyzed to determine leukocyte counts, malondialdehyde, 8-isoprostane, and cortisol concentrations. A repeated measures analysis of variance was used to examine the effects of supplement and training status over time with an alpha level of 0.05. RESULTS: There was no interaction between supplement and training status on those variables before and after exercise. However, CAJ raised resting neutrophil counts and exercise-induced leukocyte counts in the trained group (all p < 0.05). Besides, CAJ significantly reduced plasma malondialdehyde concentrations at rest and after exercise and reduced the post-exercise plasma 8-isoprostane concentration in both groups of subjects (p < 0.05). Moreover, CAJ reduced plasma cortisol after exercise in the untrained subjects. CONCLUSIONS: We suggest that 4-week CAJ supplementation can enhance exercise-induced leukocyte and resting neutrophil counts in trained men. The possible mechanism is a reduction in oxidative stress. However, the supplementation did not change the immune responses of untrained men, but it did reduce stress hormone concentrations. TRIAL REGISTRATION NUMBER: TCTR20181127002 Registered 26 November 2018 "retrospectively registered".

Toxicity Evaluation of Anacardium occidentale, the Potential Aphrodisiac Herb.

Anacardium occidentale L. leaf demonstrates sexual enhancement effect. Therefore, it can be used as the potential supplement and functional ingredient. However, the ethanolic leaf extract of this plant is a modified form of traditional application and the toxicity evaluation is required. To assess cytotoxicity of the extract, RAW 264.7 cells were treated with A. occidentale leaf extract in the concentration range between 0.625 and 10 mg/mL. Our results showed that the extract showed more than 90% cell viability at the concentration of 2.5 mg/mL after 24-hour exposure. To assure the consumption safety, the acute and subchronic toxicity must be studied. Acute toxicity showed that the extract is safe even at the highest dose of 2 g/kg in both sexes of Wistar rats. No changes in behavior, physiology, gross pathology, and histology were observed. To determine the subchronic toxicity of extract, both sexes of Wistar rats were orally given the extract at doses of 20, 100, and 500 mg/kg once daily for 90 days. No changes in body weight, food, and water intake, motor coordination, behavior, and mental alertness were observed. The significant reduction of white blood cell, platelet, and cholesterol together with increase in MCHC was observed in male rats. The reductions of white blood cell and platelet together with the elevations of hemoglobin and hematocrit were also observed in female rats. However, all changes were in normal range. The current results revealed that an ethanolic extract of A. occidentale leaf was well tolerated via oral consumption up to dose of 500 mg/kg BW for 90 days and did not produce any toxicity. Our in vitro cytotoxicity test also confirmed this safety.

Morinda citrifolia L. Leaf Extract Protects against Cerebral Ischemia and Osteoporosis in an In Vivo Experimental Model of Menopause.

We aimed to determine the protective effects against cerebral ischemia and osteoporosis of Morinda citrifolia extract in experimental menopause. The neuroprotective effect was assessed by giving M. citrifolia leaf extract at doses of 2, 10, and 50 mg/kg BW to the bilateral ovariectomized (OVX) rats for 7 days. Then, they were occluded in the right middle cerebral artery (MCAO) for 90 minutes. The neurological score, brain infarction volume, oxidative stress status, and ERK1/2 and eNOS activities were assessed 24 hours later. M. citrifolia improved neurological score, brain infarction, and brain oxidative stress status in the cortex of OVX rats plus the MCAO. No changes in ERK 1/2 signal pathway and NOS expression were observed in this area. Our data suggested that the neuroprotective effect of the extract might occur partly via the improvement of oxidative stress status in the cortex. The antiosteoporotic effect in OVX rats was also assessed after an 84-day intervention of M. citrifolia. The serum levels of calcium, osteocalcin, and alkaline phosphatase and osteoblast density in the tibia were increased, but the density of osteoclast was decreased in OVX rats which received the extract. Therefore, the current data suggested that the extract possessed antiosteoporotic effect by increasing bone formation but decreasing bone resorption.

Anticataractogenesis and Antiretinopathy Effects of the Novel Protective Agent Containing the Combined Extract of Mango and Vietnamese Coriander in STZ-Diabetic Rats.

The novel protectant against diabetic cataract and diabetic retinopathy is currently required due to the increased prevalence and therapeutic limitation. Based on the advantage of polyphenol on diabetic eye complications, we hypothesized that the combined extract of mango seed Vietnamese coriander (MPO), a polyphenol-rich substance, should possess anticataractogenesis and antiretinopathy in streptozotocin- (STZ-) diabetic rats. MPO at doses of 2, 10, and 50 mg/kg·BW were orally given to STZ-diabetic rats for 10 weeks. Lens opacity was evaluated every week throughout a study period whereas the evaluation of cataract severity and histological changes of both rat lens epithelium and retina together with the biochemical assays of oxidative stress status, aldose reductase, p38MAPK, ERK1/2, and VEGF were performed at the end of experiment. Our data showed that MPO improved cataract and retinopathy in STZ-diabetic rats. The improved oxidative stress status and the decreased p38MAPK, ERK1/2, and VEGF were also observed. Therefore, anticataractogenesis and antiretinopathy of MPO might occur partly via the decreased oxidative stress status and the suppression of aldose reductase, p38MAPK, ERK1/2, and VEGF. This study points out that MPO is the potential candidate protectant against diabetic cataract and diabetic retinopathy. However, the exploration for possible active ingredient (S) still requires further researches.

Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion.

The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg(-1) was orally given to male Wistar rats (300-350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

Laser acupuncture improves memory impairment in an animal model of Alzheimer's disease.

The burden of Alzheimer's disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer's disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180-220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days. Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer's disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential.

Cashew apple juice supplementation enhanced fat utilization during high-intensity exercise in trained and untrained men.

BACKGROUND: Exercise training is known to increase fat utilization during exercise. Diets containing antioxidants and branch chain amino acids (BCAAs) are also reported to have potential effects on fat utilization. Cashew apple juice (CAJ) comprises many nutritional components including vitamin C and BCAAs. This study aimed to investigate the effect of CAJ supplementation on substrate utilization during high-intensity exercise in trained and untrained subjects. METHODS: Ten trained and ten untrained men were randomly supplemented with either placebo (PLA) or CAJ at 3.5 ml/kg body mass (BM) /day for 4 weeks with a 4-week washout between treatments in a randomized cross-over design. Before and after the 4-week supplementations all subjects performed cycling exercise at 85% of maximal oxygen consumption for 20 minutes. At rest, before, and immediately after the exercise, venous blood samples were taken to determine glucose, insulin and lipid concentrations. Expired air was collected during the 20 minutes of exercise to calculate substrate utilization. RESULTS: During the exercise in both trained and untrained groups, there were lower carbohydrate (CHO) and higher fat oxidation rates and contributions to total energy expenditure after the CAJ supplementation compared to the PLA supplementation (p<0.05). These values were greater in the trained group than the untrained group except CHO oxidation rates (p<0.05), which were not significantly different. Moreover, in both trained and untrained groups, resting plasma vitamin C concentrations were significantly higher after the CAJ supplementation compared to the PLA supplementation, without any change after the PLA supplementation. These values were greater in the trained group than the untrained group (p<0.05). There were no significant differences in glucose, insulin or lipid concentrations between the groups' blood samples. CONCLUSION: The findings of this study suggest that CAJ supplementation enhanced fat oxidation during exercise may enhance endurance performance, but specific studies are needed to assess this possibility.

Mulberry Fruit Extract Protects against Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia.

Nowadays, the preventive strategy of vascular dementia, one of the challenge problems of elderly, has received attention due to the limitation of therapeutic efficacy. In this study, we aimed to determine the protective effect and possible mechanism of action of mulberry fruit extract on memory impairment and brain damage in animal model of vascular dementia. Male Wistar rats, weighing 300-350 g, were orally given mulberry extract at doses of 2, 10 and 50 mg/kg at a period of 7 days before and 21 days after the occlusion of right middle cerebral artery (Rt.MCAO). It was found that rats subjected to mulberry fruits plus Rt.MCAO showed the enhanced memory, the increased densities of neuron, cholinergic neuron, Bcl-2-immunopositive neuron together with the decreased oxidative stress in hippocampus. Taken all data together, the cognitive enhancing effect of mulberry fruit extract observed in this study might be partly associated with the increased cholinergic function and its neuroprotective effect in turn occurs partly via the decreased oxidative stress and apoptosis. Therefore, mulberry fruit is the potential natural cognitive enhancer and neuroprotectant. However, further researches are essential to elucidate the possible active ingredient.

Positive Modulation Effect of 8-Week Consumption of Kaempferia parviflora on Health-Related Physical Fitness and Oxidative Status in Healthy Elderly Volunteers.

Health-related physical fitness declines as the age advances. Oxidative stress is reported to contribute the crucial role on this phenomenon. This condition is also enhanced by antioxidant. Therefore, we aimed to determine the effect of Kaempferia parviflora, a plant reputed for antifatigue, longevity promotion, and antioxidant effects, on health-related quality physical fitness and oxidative status of the healthy elderly volunteers. Total 45 subjects had been randomized to receive placebo or K. parviflora extract at doses of 25 or 90 mg once daily for 8 weeks. They were determined baseline data of physical performance using 30 sec chair stand test, hand grip test, 6 min walk test, and tandem test. Serum oxidative stress markers including malondialdehde (MDA) level and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were also assayed. All assessments were performed every 4 weeks throughout the 8-week study period. The results showed that K. parviflora increased performance in 30-second chair stand test and 6 min walk test together with the increased all scavenger enzymes activities and the decreased MDA level. Therefore, K. parviflora can enhance physical fitness partly via the decreased oxidative stress. In conclusion, K. parviflora is the potential health supplement for elderly. However, further study is required.

Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers.

At present, the scientific evidence concerning the effect of Bacopa monnieri on brain activity together with working memory is less available. Therefore, we aimed to determine the effect of B. monnieri on attention, cognitive processing, working memory, and cholinergic and monoaminergic functions in healthy elderly. A randomized double-blind placebo-controlled design was utilized. Sixty healthy elderly subjects (mean age 62.62 years; SD 6.46), consisting of 23 males and 37 females, received either a standardized extract of B. monnieri (300 and 600 mg) or placebo once daily for 12 weeks. The cholinergic and monoaminergic systems functions were determined using AChE and MAO activities. Working memory was assessed using percent accuracy and reaction time of various memory tests as indices, whereas attention and cognitive processing were assessed using latencies and amplitude of N100 and P300 components of event-related potential. All assessments were performed before treatment, every four weeks throughout study period, and at four weeks after the cessation of intervention. B. monnieri-treated group showed improved working memory together with a decrease in both N100 and P300 latencies. The suppression of plasma AChE activity was also observed. These results suggest that B. monnieri can improve attention, cognitive processing, and working memory partly via the suppression of AChE activity.

Purple rice berry is neuroprotective and enhances cognition in a rat model of Alzheimer's disease.

Alzheimer's disease, a neurodegenerative disease characterized by progressive memory loss and cognitive impairment, is the most common type of dementia in aging populations due to severe loss of cholinergic neurons in a specific area. Oxidative stress is known to be involved in the pathogenesis of this condition. Therefore, the cognition-enhancing and neuroprotective effects of rice berry (Oryza sativa), a purple-pigmented rice that is rich in antioxidant substances, was evaluated. Young adult male Wistar rats, weighing 180-220 g, were orally given rice berry once daily at doses of 180, 360, and 720 mg/kg of body weight for a period of 2 weeks before and 1 week after the induction of memory deficit and cholinergic lesions with AF64A, a specific cholinotoxin, via bilateral intracerebroventricular administration. One week following AF64A administration the rats were evaluated for spatial memory, neuron density, acetylcholinesterase activity, and hippocampal lipid peroxidation products. Our results showed that rice berry could significantly prevent memory impairment and hippocampal neurodegeneration in hippocampus. Moreover, it also decreased hippocampal acetylcholinesterase activity and lipid peroxidation product formation. These results suggest that rice berry has potential as an effective agent for neurodegeneration and memory impairment in Alzheimer's disease.