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Given its antioxidant effects and central nervous system benefits, we hypothesized that RJ6601 should improve neurodegeneration in the hippocampus, a region critical for cognition and the maintenance of quality of life (QoL). To assure its safety, a single fixed dose of 2000 mg/kg BW was administered to female Wistar rats (250-450 g, 18 months old) to test the acute toxicity of RJ6601. No mortality and toxicity signs were observed. To prove that RJ6601 can protect against age-related neurodegeneration, RJ6601 at doses of 200 and 400 mg/kg BW was administered to the female Wistar rats once daily for 4 weeks. At the end of the study period, assessments were conducted to evaluate the neuron density; MDA levels; and activities of SOD, CAT, GSH-Px, AChE, total MAO, MAO-A, and MAO-B in the hippocampus. Our results reveal increased neuron density, SOD, CAT, and GSH-Px but decreased MDA, AChE, total MAO, MAO-A, and MAO-B in the hippocampi of female Wistar rats subjected to RJ6601 treatment at both doses used in this study. Therefore, RJ6601 is considered to have low toxicity and may improve neurodegeneration as well as cholinergic and monoaminergic dysfunctions. Subchronic toxicity studies and clinical trials are essential to confirm the safety of RJ6601 consumption and its health benefits.

We hypothesized that consumption of a diet containing the functional ingredient from black sticky rice, which is rich in anthocyanin, over a five-day period would improve anxiety, depression, and stress perception in adult volunteers based on the benefits of this compound. In this study, a total of 46 male and female adult volunteers with mild and moderate stress level were assigned to groups consuming a breakfast meal containing an anthocyanin-enriched functional ingredient at doses of 2 and 4 g per day for 5 days. The volunteers consumed three meals with a low DII but high DAQ-S, and the total calories consumed during the study period was 2000 kcal/day. Mental well-being, including depression, anxiety, and stress, together with AChE, MAO, Nrf2, 8OHdG, MDA, and the density of Lactobacillus and Bifidobacterium spp., were assessed at baseline and at the end of the study. Safety parameters were also examined. A diet containing both doses of the anthocyanin-enriched functional ingredient with a low DII but high DAQ-S was found to improve anxiety, depression, and stress, with changes in 8-OHdG and IL-6 levels. No other changes and toxicity-related parameters were observed. Our results show that the novel functional ingredient can improve anxiety, depression, and stress perception partly by decreasing oxidative stress and inflammation; however, randomized, double-blind, placebo-controlled studies with a larger sample size should be performed to confirm this benefit.

Backgrounds/Objectives: Despite the increasing importance of the condition of post-stroke cognitive impairment (PSCI), the current therapy efficacy is limited. Since oxidative stress and inflammation are targeted in anti-stroke therapy, we aimed to assess the protective effect against PSI of an orodispersible film loaded with silkworm pupae hydrolysate and a combined extract of holy basil and ginger (JP1), which show antioxidant, and anti-inflammation effects. Methods: Male Wistar rats (200-250 g) were administered JP1 at doses of 1, 10, and 100 mg/kg BW 45 min before a 6 h immobilization stress exposure for 14 days. Then, the right middle cerebral artery was permanently occluded (MCAO) and JP1 was continually administered for 21 days after MCAO. Spatial and non-spatial memory and the possible underlying mechanisms were also explored. Results: JP1 improved oxidative stress, inflammation, apoptosis, Erk signaling pathway, cholinergic function, and the growth of Lactobacillus and Bifidobacterium spp. in feces. These results suggest that JP1 improves PSCI, possibly involving the above mechanisms. Furthermore, serum corticosterone also decreased. Conclusions: Our results suggest that JP1 is a potential candidate for combating PSCI following exposure to stroke plus stress. However, a clear understanding of the precise active ingredient and the detailed mechanisms require further investigation.

Currently, the adjuvant therapy to optimize the restorative process after stroke is required due to the unsatisfied therapeutic efficacy. A combined extract of black sticky rice and dill showed potential in the preclinical state, so we hypothesized that it could provide clinical benefits. A three-arm, randomized, placebo-controlled study was set up to elucidate this issue. Both males and females (18-80 years old) who had experienced transient ischemic attacks or ischemic strokes within the last 5-10 days with an NIHSS score ≤ 7 and received standard treatment were randomly assigned to receive either a placebo or capsule containing a combined extract of black sticky rice and dill at a dose of 600 or 1200 mg per day. The safety parameters, movement control, and degree of disability were assessed 1, 2, and 6 weeks after the intervention, and serum stroke biomarkers were assessed at the mentioned time points, except at 2 weeks. After week 1, the high-dose (1200 mg/day) treatment group had improved NIHSSS, VCAM1, and MMP-9. Both S100β and VCAM1 also improved at week 6, while the low-dose treatment group (600 mg/day) only exhibited improved VCAM1. Therefore, a high dose of the developed adjuvant supplement improves stroke recovery by improving motor impairment by reducing endothelial dysfunction and inflammation.

Lung inflammation caused by fine particulate matter (PM), particularly PM2.5, poses a significant public health challenge, with oxidative stress and inflammation playing central roles in its pathophysiology. This study evaluates the protective effects of phytosome-encapsulated extract of purple waxy corn tassel (PPT) against PM2.5-induced lung inflammation. Male Wistar rats received PPT at doses of 100, 200, and 400 mg/kg BW for 21 days prior to exposure and continued to receive the same doses for 27 days during PM2.5 exposure. Significant reductions in inflammatory markers, including cyclooxygenase-2 (COX-II), various interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB), were observed, indicating that PPT effectively regulates the inflammatory response. Additionally, PPT improved oxidative stress markers by reducing malondialdehyde (MDA) levels and enhancing antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby restoring lung antioxidant defenses. Notably, the study revealed that PPT modulates epigenetic mechanisms, as evidenced by decreased histone deacetylase (HDAC) activity and upregulation of sirtuins in lung tissue. These epigenetic modifications likely contribute to the reduction in inflammation and oxidative stress, suggesting a multifaceted protective role of PPT that involves both direct biochemical pathways and epigenetic regulation. The interplay between reduced inflammatory signaling, enhanced antioxidant capacity, and epigenetic modulation underscores PPT's potential as a therapeutic agent for managing respiratory inflammation-related diseases and its promise for the development of future functional food products.

Due to the health benefits of polyphenols and dietary fiber in combating mental disorders, we hypothesized that a polyphenol- and dietary fiber-enriched soup (RJ6601) would improve mental wellness in a rat model of middle-aged women. To test this hypothesis, female Wistar rats aged 18 months (350-450 g) were orally administered RJ6601 at doses of 200 and 400 mg/kg BW for 28 days. The anxiolytic, antidepression, and memory-enhancing effects were assessed every 7 days throughout the study period. The neuron density and levels of activities of AChE, total MAO, MAO-A, MAO-B, MDA, SOD, CAT, GSH-Px, IL-1β, IL-6, and BDNF in the prefrontal cortex at the end of study were also investigated. Furthermore, the amounts of Lactobacillus spp. and Bifidobacterium spp. in their feces were also determined. The results revealed that the developed soup shows anxiolytic, antidepression, and memory-enhancing effects. An increased neuron density; reductions in AChE, total MAO, MAO-A, MAO-B, and MDA; and an elevation of serum BDNF, together with increased amounts of both bacterial species in feces, were also observed. Our results suggest that RJ6601 is a potential mental wellness promotion supplement that enhances BDNF levels, brain plasticity, neurotransmitter balance, and oxidative stress and inflammation status, along with improving microbiota.

To increase the value of the by-products of the canned tuna industry, the memory enhancement effect and the possible mechanisms of omega-3-rich tuna oil in bilateral ovariectomized (OVX) rats were assessed. Female rats were orally given tuna oil at doses of 140, 200, and 250 mg/kg of body weight (BW) for 28 days before OVX and for 21 days continually after OVX. Memory performance was assessed every week, whereas the parameters regarding mechanisms of action were assessed at the end of the study. All doses of tuna oil enhanced memory, docosahexaenoic acid (DHA) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities but decreased cortisol, acetylcholinesterase (AChE), malondialdehyde (MDA), and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Medium and high doses of tuna oil suppressed monoamine oxidase (MAO) but increased eNOS activity. A high dose of tuna oil suppressed gamma-aminotransferase (GABA-T) but increased glutamic acid decarboxylase (GAD) and sirtuin-1. A medium dose of tuna oil decreased homocysteine (Hcys) and C-reactive protein. No change in telomere or estradiol was observed in this study. Our results suggest the memory-enhancing effect of tuna oil in an OVX rat model of menopause. The main mechanisms may involve a reduction in oxidative stress, inflammation, and neurotransmitter regulation.

Background/objectives: Depression and anxiety are common mental health problems. Anthocyanins from berries might have an inhibitory effect on monoamine oxidase (MAO) enzymes and alleviate various mood and anxiety symptoms. This study examined the effects of a daily supplement of an anthocyanin-rich product on mental health problems., Subjects/methods: This study was a secondary analysis from a randomized, 6-week, open-label trial in 300 healthy participants aged 18-60 years who consumed 1 or 2 servings of anthocyanin-rich mulberry milk daily. The General Health Questionnaire-28 (GHQ-28) and Hospital Anxiety and Depression Scale (HADS) were used to monitor mental health problems. In addition, the saliva activity levels of MAO-A, MAO-B, and cortisol were examined at the baseline and after 6 weeks., Results: The total scores of the GHQ-28 and HADS and all their subscales decreased in both groups (all P < 0.05). The cortisol, MAO-A, and MAO-B activities decreased significantly (all P <0.05), but there were no significant differences between the groups (all P > 0.05). Significant correlations were noted between the decreased activity level of MAO-A enzyme and decreased scores from the GHQ-28 somatic subscale and the HADS depression subscale (all P < 0.05)., Conclusions: Daily consumption of anthocyanin-rich mulberry milk possibly improves mental health problems by reducing depressive and anxiety symptoms in the working population. The suppression of MAO-A activity is a possible underlying mechanism., Trial Registration: Thai Clinical Trial Registration: #TCTR20201031002., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Owing to the reputation of Kaempferia parviflora and the crucial role of oxidative stress on the disturbance of physical fitness, the effect of a functional drink containing K. parviflora extract (KP) on the physical fitness of healthy adult volunteers was assessed. Healthy male and female volunteers (19-60 years old) were randomly divided into placebo, KP90, and KP180 groups. All the subjects in KP90 and KP180 were directed to consume a functional drink containing K. parviflora extract at doses of 90 and 180 mg per serving per 80 mL, respectively. Parameters of physical fitness, including cardiovascular endurance, muscular strength and endurance, flexibility, and body composition, together with changes in lactate, creatinine kinase, and oxidative stress markers were assessed before the intervention, and at 6 and 12 weeks of intervention. The oxidative stress markers, creatine kinase, and lactate were also measured. Subjects who consumed the developed drink had increased VO 2 max and improved performance in a timed shuttle run test and 5 min distance run, and exhibited decreased oxidative stress and lactate; therefore, K. parviflora extract can be successfully used for developing a KP drink to improve cardiorespiratory fitness and physical performance by improving oxidative stress and lactate.

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.

The anti-dementia effect following ischemic stroke with metabolic syndrome (MetS) of the polyherbal functional ingredient comprising ginger, Chinese date, and wood ear mushroom (GCJ) was hypothesized due to its neuroprotective effect against stroke. This study was performed to test this hypothesis and to explore the underlying mechanism. Male Wistar rats weighing 180-220 g were induced metabolic syndrome (MetS) with a 16-week high-carbohydrate high-fat diet (HCHF) feeding. The rats with MetS characteristics were orally administered GCJ at various doses (GCJ100, GCJ200, and GCJ300 mg kg -1 BW) 21 days pre-induction and 21 days post-induction of reperfusion injury (I/R) at the right middle cerebral artery (MCAO). Memory was evaluated every 7 days during the study period. At the end of the study, neuron density, AChE activity, and the expressions of eNOS, BDNF, and pERK/ERK in the prefrontal cortex, and hippocampus were also determined. MetS rats with GCJ treatment improved memory impairment, enhanced neuron density, and increased the expressions of eNOS, BDNF, and pERK/ERK but suppressed AChE in both areas. Therefore, the anti-dementia effect following ischemic stroke with metabolic syndrome of GCJ may involve the improvement of AChE, eNOS, BDNF, pERK/ERK, and neural plasticity. However, this required confirmation by clinical study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 Thuntiva Nakyam et al.)

The prevalence of stroke under stress conditions is rising and the severity of stroke is increasing. Owing to the limitation of the current therapeutic strategy, a novel effective strategy for treating this condition is needed. In this study, we explored the neuroprotective effect of an orodispersible film derived from a rice polymer loaded with silkworm pupae and the combined extract of holy basil and ginger (JP1). Male Wistar rats weighing 200-250 g were administered JP1 at the doses of 1, 10, and 100 mg/kg BW 45 min prior to an exposure to a 6-h immobilization stress for 14 days. Permanent, occlusion of the right middle cerebral artery (MCAO) was performed, and JP1 was administered continually for 21 days after MCAO. Assessments of the brain infarction volume, oxidative stress, inflammation, and apoptosis in the cerebral cortex were carried out 24 h after MCAO. Neurological severity scores were also determined for the rats every 7 days after MCAO until the end of the study period. The results clearly showed that all doses of JP1 decreased the brain infarct volume, oxidative stress, inflammation, and apoptosis and improved neurological deficits. Therefore, JP1 is a potential novel neuroprotective supplement for combating ischemic stroke under stress conditions. However, a clinical trial is essential to confirm this beneficial effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study is aimed to investigate whether tuna protein hydrolysate (TPH) supplementation could alleviate cardiovascular complications induced by a high-fat diet (HFD) in rats. Rats were fed a HFD for 16 weeks and given TPH (100 mg/kg, 300 mg/kg, or 500 mg/kg) or metformin (100 mg/kg) (n = 8) for the last four weeks. TPH had the following effects: resolved their impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, and hypertension (p < 0.05); alleviated left ventricular dysfunction and hypertrophy (p < 0.05), and vascular dysfunction and hypertrophy (p < 0.05); adipocyte hypertrophy; increases in circulating leptin and tumor necrosis factor (TNF-α) were mitigated (p < 0.05); increased renin-angiotensin system (RAS), oxidative stress, and decreased nitric oxide metabolites were modulated (p < 0.05). TPH restored the expression of angiotensin II receptor type 1 (AT1R)/NADPH oxidase 2 (NOX2), endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor γ (PPARγ)/the nuclear factor kappa B (NF-κB) protein in cardiovascular tissue (p < 0.05). In metabolic syndrome (MS) rats, metformin and TPH had comparable effects. In conclusion, TPH alleviated cardiovascular complications related to MS. It suppressed RAS, oxidative stress, and inflammation that were associated with modulation of AT1R/NOX2, eNOS, Nrf2/HO-1, and PPARγ/NF-κB expression., (© 2023. The Author(s).)

The human microbiota-gut-brain axis has an enormous role in the maintenance of homeostasis and health. Over the last two decades, it has received concerted research attention and focus due to a rapidly emerging volume of evidence that has established that impairment within the microbiota-gut-brain axis contributes to the development and progression of various diseases. Stroke is one of the entities identified to be associated with microbiota-gut-brain axis impairment. Currently, there are still limitations in the clinical treatment of stroke, and the presence of a non-nervous factor from gut microbiota that can alter the course of stroke presents a novel strategy towards the search for a therapeutic silver bullet against stroke. Hence, the aim herein, was to focus on the involvement of microbiota-gut-brain axis impairment in the pathogenesis stroke as well as elucidate its implications as a potent therapeutic target against stroke. The findings of studies to date have revealed and extended the role microbiota-gut-brain axis impairment in the pathogenesis of stroke, and studies have identified from both clinical and pre-clinical perspectives targets within the microbiota-gut-brain axis and successfully modulated the outcome of stroke. It was concluded that the microbiota-gut-brain axis stands as potent target to salvage the neurons in the ischemic penumbra for the treatment of stroke. Assessment of the microbiota profile and its metabolites status holds enormous clinical potentials as a non-invasive indicator for the early diagnosis and prognosis of stroke., (©2023 BMFH Press.)

Despite an increase in the coexistence of metabolic syndrome (MetS) and psychological disorders, together with their great impact on socio-economic burdens, no protective strategies that focus on these situations are available. Due to the role of oxidative stress in the pathophysiology of metabolic syndrome (MetS) and psychological disorders, we hypothesized that substances possessing antioxidant activity such as the novel functional ingredients from Anacardium occidentale (AO) could mitigate common psychological disorders in MetS rats. Male Wistar rats, weighing 200-250 g, were induced with MetS through a 12-week high-fat and high-cholesterol diet (HFHC). Then, they were given AO orally via a gastric gavage needle at doses of 1, 10 and 100 mg/kg BW for 14 days. Spatial memory, anxiety, depression, and sleep behaviors, together with changes in oxidative stress status and neurotransmitters, were assessed. All doses of AO significantly improved memory, anxiety, and sleep, together with the suppression of oxidative stress, AChE, and GABA-T in the cerebral cortex and hippocampus. These results suggest the protective effect of AO against anxiety, insomnia, and memory impairment that coexist with the MetS condition via an improvement in oxidative stress and the functions of the cholinergic and GABAergic systems. However, this benefit requires clinical confirmation.

Due to great demand for memory enhancers, the memory-enhancing effects and the possible underlying mechanisms of the functional ingredients derived from the combined extract of Polygonum odoratum and Morus alba were investigated. A total of 45 participants randomly received either a placebo or the developed herbal supplement at a dose of 50 or 1500 mg/day. The consumption was done once daily for 8 weeks. Working memory was assessed via both an event-related potential and computerized battery tests at baseline and at the end of the 8-week study period. Acetylcholinesterase (AChE) and monoamine oxidase type A and type B (MAO-A, MAO-B) levels were also measured at the end of the study. The subjects who consumed the supplement containing a developed functional ingredient at a dose of 1500 mg/day showed reduced latencies but increased amplitudes of N100 and P300. An improvement in working memory and the suppression of AChE, MAO-A, and MAO-B activities were also observed. Therefore, this study clearly demonstrates the cognitive enhancing effect of the developed herbal congee, which may be associated with the suppressions of AChE and both types of MAO.

Currently, the prevalence of stroke with metabolic syndrome (MetS) is increasing and the current therapeutic efficiency is still limited. Therefore, the applications of herbal recipes have gained much attention. The polyherbal recipe containing ginger, Chinese date, and wood ear mushroom is reputed for atherosclerosis and stroke prevention. It has been long-term consumed without scientific support. Therefore, this study was carried out to determine the neuroprotective effect and its mechanisms in animal model of ischemic stroke with MetS. Male Wistar rats weighing 180-220 g were exposed to a 16-week high-fat high-carbohydrate feeding. The rats with the MetS characteristic were exposed to a temporary occlusion of the right middle cerebral artery (MCAO) for 90 minutes. They were orally fed with the polyherbal recipe (GCJ) at the doses of 100, 200, and 300 mg/kg BW for 21 days and assessed the neurological deficit, ion volume, cortical neuron density in the cerebral cortex, oxidative stress status, inflammation, and expressions of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1). The results showed that GCJ significantly improved all mentioned parameters. Therefore, GCJ is the potential neuroprotectant against ischemic stroke with MetS. The underlying mechanisms may involve the reduction of oxidative stress, inflammation, and the modification of epigenetic mechanism via the reduction of HDAC3 and DNMT1. However, further clinical investigation is essential to confirm this positive modulation effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thuntiva Nakyam et al.)

The cassava root is an important global agro-industrial crop that yields cassava leaf as a left-over co-product of interest for further development as a sustainable resource of health and cosmeceutical active compounds. This work aimed to investigate the cosmeceutical potential and chemical composition of an ethanolic cassava leaf extract (BM). rutin, apigenin, and kaempferol were found to be major constituents via HPLC-DAD UV analysis. Interestingly, the multiple beneficial bioactivities of BM for cosmeceutical applications were manifested in a dose-dependent manner, including anti-oxidation in a 2,2-diphenyl-1-picrylhydrazyl assay, anti-melanogenesis in B16 melanoma cells, collagen synthesis enhancement in human fibroblasts, and anti-adipogenesis in 3T3-L1 adipocytes. Furthermore, the potential of the collagen synthesis enhancement of BM and rutin was significant when compared to ascorbic acid. Additionally, a UV filter property comparable to BEMT with characteristics of board spectral absorption and constant high absorptivity throughout all UV wavelength ranges was exhibited by UV-visible spectrophotometric analysis. In conclusion, the cassava leaf was found to be a potential natural cosmeceutical active agent with multiple cosmeceutical-related bioactivities with respect to a substantial composition of bioactive flavonols. These obtained data will support and encourage the further study and development of cassava leaves as potential economic and sustainable sources of bioactive agents for health and cosmeceutical applications.

Due to the increase of stress-related memory impairment accompanying with the COVID-19 pandemic and financial crisis, the prevention of cognitive decline induced by stress has gained much attention. Based on the evidence that an anthocyanin-rich mulberry milk demonstrated the cognitive enhancing effect, we hypothesized that it should be able to enhance memory in working-age volunteers who are exposed to working stress. This study is an open-label, two-arm randomized study. Both men and women volunteers at age between 18 and 60 years old were randomly assigned to consume the tested product either 1 or 2 servings daily for 6 weeks. All subjects were assessed for cortisol, acetylcholinesterase (AChE), monoamine oxidase (MAO), monoamine oxidase type A (MAO-A), and monoamine oxidase type B (MAO-B) in saliva, and their working memory was determined both at baseline and at a 6-week period. The results showed that the working memory of subjects in both groups was enhanced at the end of the study period together with the reduction of saliva cortisol. The suppression of AChE, MAO, and MAO-A was also observed in subjects who consumed the tested product 2 servings daily. Therefore, we suggest the memory enhancing effect of an anthocyanin-rich mulberry milk. The possible mechanism may occur primarily via the suppression of cortisol. In addition, the high dose of mulberry milk also suppresses AChE, MAO, and MAO-A., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wipawee Thukham-mee et al.)

The prevalence of dementia following cerebral ischemia in metabolic syndrome (MetS) condition is increasing, and most of the cases are often severe. Unfortunately, no effective strategy for treating this condition is available. Based on the positive modulation effect of a polyphenol-rich substance on dementia and the improvement in bioavailability and stability of polyphenols induced by the phytosome technique together with the use of the synergistic concept, we hypothesized that a phytosome containing the combined extract of mulberry fruit and ginger (PMG) should mitigate dementia and memory impairment following ischemic stroke in MetS. MetS was induced in male Wistar rats weighing 180-200 g by exposure to a 16-week feeding period of high-carbohydrate high-fat (HCHF) diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg·kg -1 BW 21 days before and 21 days after the occlusion of the right middle cerebral artery (Rt. MCAO). Then, their spatial memory was determined and the possible underlying mechanisms explored via the alterations of acetylcholinesterase (AChE), neuron density, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and signal transduction via extracellular signal-regulated kinase (ERK) pathway in both the cerebral cortex and the hippocampus. It was found that PMG significantly enhanced memory. It also decreased AChE, IL-6, and MDA but increased SOD, CAT, GSH-Px, neuron density, and phosphorylation of ERK. These data suggested the cognitive enhancing effect of PMG. The possible underlying mechanisms might occur partly via the improvement of cholinergic function via the ERK pathway together with the decrease in neurodegeneration induced by the reduction of oxidative stress and inflammation. However, a subchronic toxicity study is also required to assure the safety of PMG consumption before moving forward to a clinical trial study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jintanaporn Wattanathorn et al.)

The prevalence of ischemic stroke in metabolic syndrome (MetS) is continually increasing and produces a great impact on both qualities of life and annual healthcare budget. Due to the efficiency limitation of the current therapeutic strategy, the poor availability of polyphenol substances induced by the first pass effect and the beneficial effects of mulberry fruit and ginger on brain and MetS-related diseases together with the synergistic concept, the neuroprotective effect against ischemic stroke in MetS condition of phytosome containing the combined extract of mulberry fruit and ginger (PMG) has been considered. To explore the neuroprotective effect and possible underlying mechanism of PMG on brain damage in cerebral ischemic rat with MetS, male Wistar rats were induced MetS by high-carbohydrate high-fat diet (HCHF) for 16 weeks and subjected to the cerebral ischemia/reperfusion injury (CIRI) at the right middle cerebral artery (Rt. MCAO). PMG at doses of 50, 100, and 200 mg/kg were orally fed with for 21 days, and they were assessed brain damage, neurological deficit score, and the changes of oxidative stress markers, inflammatory markers, PPAR γ expression, and epigenetic modification via DNMT-1 were performed. All doses of PMG significantly improved brain infarction, brain edema, and neurological deficit score. In addition, the reduction in DNMT-1, MDA level, NF- κ B, TNF α , and C-reactive protein together with the increase in SOD, CAT, and GPH-Px activities, and PPAR γ expression in the lesion brain were also observed. The current data clearly revealed the neuroprotective effect against cerebral ischemia with MetS condition. The possible underlying mechanism might occur partly via the suppression of DNMT-1 giving rise to the improvement of signal transduction via PPAR γ resulting in the decreasing of inflammation and oxidative stress. In conclusion, PMG is the potential neuroprotectant candidate against ischemic stroke in the MetS condition. However, the clinical trial is still essential., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Nut Palachai et al.)

Members of the China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research used the video conference platform to exchange and discuss the advantages of traditional medicine through the form of score exchange and report, and research and develop the amount and issues of the therapeutic COVID-19 products of concern. This paper mainly reviews the achievements of the implementation of the epidemic prevention and control plan, advances of scientific basic studies on SARS-CoV-2, analysis and screening of potential targets and pathways of antiviral compounds based on network pharmacology and development of antiviral food dual-use products. The authors believe that the declaration of the (10 + 3) special meeting of national leaders on epidemic prevention and control should raise the medical and pharmaceutical issues of common concern. It is the responsibility of our joint laboratory members to accelerate the development of traditional medicine research and industry. Also the authors believe that this exchange will certainly promote the development of the cause of cooperation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Currently, cognitive enhancers are considered necessary because they play a critical role in daily and social behaviors. The cognitive-enhancing effect of mulberry milk has gained attention due to the cognitive-enhancing effect of this anthocyanin-rich substance and the cognitive-enhancing effect of mulberry fruit in animal models. However, the effect of anthocyanin-rich mulberry milk in clinical trials especially in children is still unknown. This study was a randomized double-blind crossover intervention. A total of forty-six healthy, normal, cognitive subjects aged 6-12 years old were provided mulberry milk (containing mulberry 10 g) or placebo milk (50 mL). Attention and cognitive function were assessed using the auditory odd ball paradigm of event-related potential, whereas working memory was assessed using a computerized battery test. The assessment was performed at baseline and then at 1.5 and 3 hours postdosing. At the end of study period, the activities of acetylcholinesterase (AChE) and monoamine oxidase (MAO) together with that of saliva cortisol were determined. Following mulberry milk intervention, the decreased N100 latency and the increased P300 amplitude were increased both at 1.5 and 3 hours after dosing. The decreased response time of digit updating was observed both at 1.5 and 3 hours after dosing, whereas the decreased response time of picture updating was observed at 3 hours after dosing. In addition, the reduction of saliva cortisol was also observed at both periods. The improvement of attention and cognitive processing capabilities together with the working memory suggests the cognitive-enhancing potential of mulberry milk for school-age children. The possible underlying mechanism may be associated partly with the reduction of cortisol, a stress hormone., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Wipawee Thukham-mee et al.)

Many studies have been conducted on the bioactive compounds of rice seeds, however, there is limited information on the bioactive compounds of rice sprouts. This study focused on the age effect on the phytochemical content of white and black glutinous rice sprouts harvested between 5 and 25 days old. We assessed yield, total phenolic content, total flavonoid content, total anthocyanin content, total chlorophyll content, and proximate analysis. HPLC results identified protocatechuic acid, vanillic acid, and rutin in the sprouts of both cultivars, ranging between 0.56-1.58, 0.65-7.69, and 0.47-1.68 mg/g extract, respectively. The amount of bioactive compounds and proximate compositions in black glutinous rice were generally higher than white glutinous rice in an age-dependent manner ( p < 0.05). At 5-7 days, black glutinous rice contained the highest total anthocyanin content, while white glutinous rice contained the highest total phenolic content and total flavonoid content ( p < 0.05). High total chlorophyll content was initially detected in white glutinous rice at a younger age than black glutinous rice ( p < 0.05), while total chlorophyll content in both cultivars was not significantly different. Our study confirms the presence of phytoconstituents in the rice sprouts of white and black glutinous rice and their potential as functional foods and for being further development as natural health products.

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- κ B, 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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Jintanaporn Wattanathorn et al.)

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF- α , oxidative stress status, PPAR- γ , and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF- α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR- γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR- γ , and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Nut Palachai et al.)

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".

Currently, the therapeutic strategy against metabolic syndrome and its complications is required due to the increasing prevalence and its impact. Due to the benefits of both mulberry fruit extract and encapsulation technology, we hypothesized that encapsulated mulberry fruit extract (MME) could improve metabolic parameters and its complication risk in postmenopausal metabolic syndrome. To test this hypothesis, female Wistar rats were induced experimental menopause with metabolic syndrome by bilateral ovariectomy (OVX) and high-carbohydrate high-fat (HCHF) diet. Then, they were orally given MME at doses of 10, 50, and 250 mg/kg BW for 8 weeks and the parameters, such as percentage of body weight gain, total cholesterol, triglycerides, HDL-C, LDL-C, atherogenic index, fasting blood glucose, plasma glucose area under the curve, serum angiotensin-converting enzyme (ACE), oxidative stress status, histology, and protein expression of PPAR- γ , TNF- α , and NF- κ B in adipose tissues were determined. MME improved body weight gain, adiposity index, glucose intolerance, lipid profiles, atherogenic index, ACE, oxidative stress status, and protein expression of TNF- α and NF- κ B. Moreover, MME attenuated adipocyte hypertrophy and enhanced PPAR- γ expression. Taken altogether, MME decreased metabolic syndrome and its complication via the increased PPAR- γ expression. Therefore, MME is the potential candidate for improving metabolic syndrome and its related complications. However, further research in clinical trial is still necessary.

Despite the increase in cognitive deficit following stroke in metabolic syndrome (MetS) condition, the therapeutic strategy is still limited. Since oxidative stress and neuroinflammation play the crucial roles on the pathophysiology of aforementioned conditions, the cognitive enhancing effect of the combined extract of Oryza sativa and Anethum graveolens was considered based on their antioxidant, anti-inflammation, and neuroprotective effects together with the synergistic effect concept. Male Wistar rats weighing 180-220 g were induced metabolic syndrome-like condition by using a high-carbohydrate high-fat diet (HCHF diet). Then, reperfusion injury following cerebral ischemia was induced by the occlusion of right middle cerebral artery and treated with the combined extract of O. sativa and A. graveolens (OA extract) at doses of 0.5, 5, and 50 mg/kg BW once daily for 21 days. Spatial memory was assessed every 7 days throughout the experimental period. At the end of the study, neuron and glial fibrillary acidic protein- (GFAP-) positive cell densities, the oxidative stress status, AChE, and the expression of proinflammatory cytokines (TNF- α , IL-6) in the hippocampus were determined. The results showed that OA extract at all doses used in this study significantly improved memory together with the reductions of MDA, TNF- α , IL-6, AChE, and density of GFAP-positive cell but increased neuron density in the hippocampus. Taken together, OA is the potential cognitive enhancer in memory impairment following stroke in MetS condition. The possible underlying mechanism may occur partly via the reductions of oxidative stress status, GFAP-positive cell density, and neuroinflammatory cytokines such as TNF- α and IL-6 together with the suppression of AChE activity in the hippocampus. This study suggests that OA is the potential functional ingredient to improve the cognitive enhancer. However, further clinical research is required.

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.

Based on the benefit of polyphenolic compounds on osteoporosis, we hypothesized that the polyphenol-rich herbal congee containing the combined extract of Morus alba and Polygonum odoratum leaves should improve bone turnover markers in menopausal women. To test this hypothesis, a randomized double-blind placebo-controlled study was performed. A total of 45 menopausal participants were recruited in this study. They were randomly divided into placebo, D1, and D2 groups, respectively. The subjects in D1 and D2 groups must consume the congee containing the combined extract of M. alba and P. odoratum leaves at doses of 50 and 1500 mg/day, respectively. At the end of an 8-week consumption period, all subjects were determined serum bone markers including calcium, alkaline phosphatase, osteocalcin, and beta CTX. In addition, the hematological and blood clinical chemistry changes, and total phenolic content in the serum were also determined. The results showed that the menopausal women in D2 group increased serum alkaline phosphatase, osteocalcin, and total phenolic compounds content but decreased CTX level. Clinical safety assessment failed to show toxicity and adverse effects. Therefore, herbal congee containing the combined extract of M. alba and P. odoratum leaves is the potential functional food that can decrease the risk of osteoporosis.

In this study, we aimed to assess the effect and possible underlying mechanism of Anacardium occidentale leaves extract on male sexual behaviors in stress-exposed rats. Male Wistar rats were orally given A. occidentale extract at doses of 25, 100, and 200 mg/kg BW before 12-hour-immobilization exposure for 14 days. Sexual behaviors, serum testosterone and corticosterone levels, TH-positive cells density in nucleus accumbens (NAc) and ventral tegmental area (VTA), MAO-B activity in NAc and medial preoptic area (MPOA), testis histology together with phosphodiesterase type-5 ( PDE-5) activity, and endothelial nitric oxide synthase (eNOS) expression in penis were evaluated after treatment. All doses of extract improved male sexual behaviors, suppressed MAO-B in NAc, enhanced TH-positive cells density in NAc, suppressed PDE-5 in penis, and enhanced interstitial cell of Leydig. The increase of serum testosterone, TH-positive cells density in VTA, eNOS expression in penis, and the decreased serum corticosterone were observed at some doses. Therefore, the sexual enhancing effect of extract occurred mainly via the improved dopaminergic and testicular functions. PDE-5 suppression in penis also played the role especially in the increased intromission behavior. Therefore, A. occidentale leaves extract is the potential protective agent against sexual dysfunction. However, further researches are necessary.

Currently, the suppression of oxidative stress and inflammation is considered as the treatment targets of spinal cord injury due to their roles on the hindrance of recovery process. Since laser acupuncture decreased oxidative stress and enhanced the survival of neurons from oxidative stress damage and GV2 stimulation was selected as one stimulated acupoint in order to enhance the recovery of spinal cord injury, we hypothesized that laser acupuncture at GV2 should enhance the recovery of spinal cord injury. To test this hypothesis, male Wistar rats were induced spinal cord injury at T10 level and they were exposed to a 10 minute-stimulation at GV2 by yellow laser. Laser acupuncture was performed at 0.25 and 1, 2, 6, and 12 hours after spinal cord injury. Then, the stimulation was performed once daily for 7 days. Locomotor assessment was carried out on days 3 and 7 after injury. At the end of study period, the densities of polymorphonuclear of leukocyte, Bax, Caspase-3, Bcl-2, and BDNF positive stained cells in ventral horn of spinal cord were determined. Cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and oxidative stress status was also assessed. The results showed that laser acupuncture at GV2 increased BBB score, gross motor score, and densities of Bcl-2 and BDNF positive stained cells but decreased density with polymorphonuclear leukocyte, the densities of Bax and Caspase-3 positive stained cells, COX-2 level, and oxidative stress status in ventral horn of the lesion spinal cord. The reduction of serum COX-2 was also decreased. Therefore, GV2 stimulation by yellow laser might enhance the recovery of spinal cord via the increase in BDNF and the decrease in inflammation, apoptosis, and oxidative stress status in the lesion spinal cord.

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.

The novel therapeutic strategy against autism is essential due to the limited therapeutic efficacy. Based on the benefit of laser acupuncture at HT7 acupoint on the neurological disorders related with oxidative stress and inflammation, its benefit on oxidative stress, neuroinflammation, and GABAergic/glutamatergic imbalance in cerebellum of autism have been considered. To elucidate this issue, male rat pups were induced autistic-like conditions by valproic acid (VPA) and treated with laser acupuncture at HT7 acupoint once daily between postnatal Day 14 and Day 40. At the end of study, the changes of oxidative stress markers, the expressions of cytokines interleukin 6 (IL-6) and glutamic acid decarboxylase (GAD) proteins (65 kDa and 67 kDa) together with gamma-aminobutyric acid transaminase (GABA-T) activity and density of Purkinje cell in the cerebellum were assessed. The results showed that laser acupuncture HT7 decreased oxidative stress, IL-6 expression, and GABA-T activity but increased the expressions of GAD 65 kDa together with the density of Purkinje cells in the cerebellum. Therefore, laser acupuncture at HT7 is the potential strategy to improve the cerebellar disorders in VPA-rat model of autism. The mechanism may occur partly via the decrease of oxidative stress status, inflammation, and the improved GABAergic function., (Copyright © 2017. Published by Elsevier B.V.)

Background: Currently, food supplements to improve age-related dementia are required. Therefore, we aimed to determine the effect of the combined extract of Cyperus rotundus and Zingiber officinale (CP1) on the improvement of age-related dementia in rats with AF64A-induced memory deficits., Methods: Male Wistar rats weighing 180-200 g were orally given CP1 at doses of 100, 200 and 300 mg.kg -1 BW for a period of 14 days after bilateral intracerebroventricular administration of AF64A. Spatial memory was assessed in all rats every 7 days throughout the 14 day-experimental period. At the end of the study, neuronal density, acetylcholinesterase (AChE) activity, oxidative stress status and the activation of MAPK cascades in the hippocampus were determined., Results: Enhanced memory, increased neuronal density, decreased AChE activity and decreased oxidative stress status together with activated pERK1/2 were observed in the hippocampus of CP1-treated rats. These results suggested that CP1 might improve memory via enhanced cholinergic function and decreased neurodegeneration and oxidative stress., Conclusions: CP1 is a potential novel food supplement for dementia. However, further investigations on the subchronic toxicity of CP1 and drug interactions are required.

This study aimed to determine the protective effect of cashew nut-derived protein hydrolysate with high dietary fiber (AO) in cerebral ischemic rats induced by the occlusion of right middle cerebral artery (Rt.MCAO). Acute toxicity was determined and data showed that LD 50 of AO > 5000 mg/kg BW. To determine the cerebroprotective effect of AO, male Wistar rats were orally given AO at doses of 2, 10, and 50 mg/kg for 14 days and subjected to Rt.MCAO. Brain infarction volume, neurological score, spatial memory, serum lipid profiles, and C-reactive protein together with the brain oxidative stress status were assessed. All doses of AO significantly decreased brain infarction in cortex, hippocampus, and striatum together with the decreased oxidative stress status. The improvement of spatial memory and serum C-reactive protein were also observed in MCAO rats which received AO at all doses. In addition, the decreased serum cholesterol, TG, and LDL but increased HDL were observed in MCAO rats which received high dose of AO. Taken all together, AO is the potential protectant against cerebral ischemia. The improvement of oxidative stress, inflammation, and dyslipidemia might play roles in the actions. However, further researches are required to understand the precise underlying mechanism.

Currently, the neuroprotectant and memory-enhancing agent for menopausal women with metabolic syndrome is required. Based on the advantages of polyphenolics on numerous changes observed in menopause with metabolic syndrome and the encapsulation method, we hypothesized that microencapsulated mulberry fruit extract (MME) could protect brain damage and improve memory impairment in an animal model of menopause with metabolic syndrome. To test this hypothesis, MME at doses of 10, 50, and 250 mg/kg was given to female Wistar rats which were induced experimental menopause with metabolic syndrome by bilateral ovariectomy (OVX) and fed with high-carbohydrate high-fat (HCHF) diet for 8 weeks. Spatial memory together with neuron density, oxidative stress status, acetylcholinesterase, and phosphorylation of Erk in the hippocampus was assessed at the end of the study. It was found that MME decreased memory impairment, oxidative stress status, and AChE activity but increased neuron density and Erk phosphorylation in the hippocampus. Therefore, the neuroprotective and memory-enhancing effects of MME might partly involve the enhanced cholinergic function and Erk phosphorylation but decreased oxidative stress status in hippocampus. Therefore, MME is the potential novel neuroprotectant and memory-enhancing agent for menopause with metabolic syndrome. However, further research especially clinical trial is still necessary.

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.

The neuroprotectant and memory enhancer supplement for menopause is required due to the side effects of hormone replacement therapy. Since purple waxy corn cob and pandan leaves exert antioxidant and acetylcholinesterase inhibition (AChEI) effects, we hypothesized that the combined extract of both plants (PCP) might provide synergistic effect leading to the improved brain damage and memory impairment in experimental menopause. To test this hypothesis, female Wistar rats were ovariectomized bilaterally and orally given various doses of the functional drink at doses of 20, 40, and 80 mg/kg for 28 days. The animals were assessed nonspatial memory using object recognition test every 7 days throughout the study period. At the end of study, they were assessed with oxidative stress status, AChEI, neuron density, and ERK1/2 signal in the prefrontal cortex (PFC). Interestingly, all doses of PCP increased object recognition memory and neuron density but decreased oxidative stress status in PFC. Low dose of PCP also decreased AChE activity while medium dose of PCP increased phosphorylation of ERK1/2 in PFC. Therefore, the improved oxidative stress status and cholinergic function together with signal transduction via ERK in PFC might be responsible for the neuroprotective and memory-enhancing effects of PCP.

In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Due to the crucial role of oxidative stress in the stress-induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect of Nelumbo nucifera flowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250-350 g, were orally given N. nucifera extract at doses of 10, 10, and 200 mg·kg(-1) 45 minutes before the exposure to 12-hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO-A and MAO-B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed that N. nucifera extract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO-A and MAO-B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress-related brain damage and dysfunction of the extract. Therefore, N. nucifera extract is the potential neuroprotective and memory enhancing agent. However, further researches are still required.

Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg(-1) BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect.

The therapeutic strategy against autism, a severe neurological development disorder, is one of the challenges of this decade. Recent findings show that oxidative stress plays a crucial role on the pathophysiology of autism, and laser acupuncture at Shenmen (HT7) can improve oxidative status in many neurological disorders. Therefore, we aimed to assess the effect of laser acupuncture at HT7 on behavior disorders and oxidative stress status in the cortex, striatum, and hippocampus of the valproic acid rat model of autism. Laser acupuncture was performed once daily during postnatal day (PND) 14-PND 40. Behavioral tests including rotarod, open-field, learning and memory, and social behavior tests were performed during PND 14-PND 40. At the end of study, brain oxidative status including malondialdehyde levels and the activities of superoxide dismutase, catalase, and glutathione peroxidase were determined in the cortex, striatum, and hippocampus. Laser acupuncture at HT7 significantly improved autistic-like behaviors. Decreased malondialdehyde levels were observed in all areas mentioned above, however, increased glutathione peroxidase activity was observed only in the striatum and hippocampus. No changes in superoxide dismutase and catalase activities were observed in any investigated area of the brain. Therefore, our study suggests that laser acupuncture at HT7 partly mitigates autistic-like symptoms via improved oxidative status., (Copyright © 2015. Published by Elsevier B.V.)

[Purpose] We aimed to evaluate the effects of Phyllanthus amarus (PA) on oxidative stress and damage, inflammation, and soreness in muscle after a single session of moderate-intensity exercise. [Subjects and Methods] Twelve men randomly participated in 2, three-day phases with a one-week washout period. On the first day, participants consumed two capsules of PA or placebo control (CTL) before 20 min of cycling. They then consumed four capsules on the same day after exercise and six capsules/day for the next two days. Blood samples were obtained before, immediately after exercise and 24 h and 48 h after exercise. The pain tolerance was measured at both legs. [Results] Plasma vitamin C levels in the PA group were higher than those in the CTL group after exercise. At 48 h after exercise, vitamin C levels were higher in the PA group, but those in the CTL group were lower than the pre-exercise levels. However, plasma levels of creatine kinase were increased in both groups after exercise compared with the pre-exercise levels. The neutrophil count was higher immediately after exercise than the pre-exercise levels in the CTL group. [Conclusion] Acute supplementation with PA improves antioxidant status after a single session of moderate-intensity exercise.

Aphrodisiacs are required to improve male sexual function under stressful conditions. Due to the effects of oxidative stress and dopamine on male sexual function, we hypothesized that Moringa oleifera leaves might improve male sexual dysfunction induced by stress. Therefore, the effects on various factors playing important roles in male sexual behavior, such as antioxidant effects, the suppression of monoamine and phosphodiesterase type 5 (PDE-5) activities, serum testosterone and corticosterone levels, and histomorphological changes in the testes, of a hydroethanolic extract of M. oleifera leaves were investigated. Various doses of extract including 10, 50, and 250 mg/kg body weight (BW) were given orally to male Wistar rats before exposure to 12 h-immobilization stress for 7 d. The results demonstrated that the extract showed both antioxidant and monoamine oxidase type B (MAO-B) suppression activities. At 7 d of treatment, the low dose of extract improved sexual performance in stress-exposed rats by decreasing intromission latency and increasing intromission frequency. It also suppressed PDE-5 activity, decreased serum corticosterone level, but increased serum testosterone, numbers of interstitial cells of Leydig and spermatozoa. The increased numbers of interstitial cells of Leydig and spermatozoa might have been due to the antioxidant effect of the extract. The increased sexual performance during the intromission phase might have been due to the suppression of MAO-B and PDE-5 activities and increased testosterone. Therefore, M. oleifera is a potential aphrodisiac, but further research concerning the precise underlying mechanisms is still needed.

Currently, the therapeutic strategy against memory deficit induced by alcoholism is not satisfactory and is expensive. Therefore, an effective, low-cost strategy is required. On the basis of the memory-enhancing effect of stimulation of the HT7 acupoint, we aimed to determine whether acupuncture at the HT7 acupoint can reduce alcoholism-induced memory impairment. The possible underlying mechanism was also explored. Alcoholism was induced in male Wistar rats weighing 180-220 g. The alcoholic rats received either acupuncture at HT7 or sham acupuncture for 1 minute bilaterally once daily for 14 days. Their spatial memory was assessed after 1 day, 7 days, and 14 days of treatment. At the end of the study, the malondialdehyde level and the activities of catalase, superoxide dismutase, glutathione peroxidase, and acetylcholinesterase enzymes in the hippocampus were determined using colorimetric assays. The results showed that acupuncture at HT7 significantly decreased the acetylcholinesterase activity and the malondialdehyde level, but increased the activities of catalase, superoxide dismutase, and glutathione peroxidase in the hippocampus. These results suggest that acupuncture at HT7 can effectively reduce the alcoholism-induced memory deficit. However, further studies concerning the detailed relationships between the location of the HT7 acupoint and the changes in the observed parameters are required., (Copyright © 2015. Published by Elsevier B.V.)

Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg(-1)BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

Based on the protective effect of the combined extract of purple waxy corn and ginger (PWCG) on oxidative stress related disorders in diabetic condition, we aimed to determine the effect of PWCG on the functional, biochemical, and structural change of the lesion nerve in streptozotocin- (STZ-) diabetic rats. PWCG at doses of 100, 200, and 300 mg·kg(-1) BW were orally given to STZ-diabetic rats which were subjected to chronic constriction (CCI) at right sciatic nerve for 21 days. The blood sugar was assessed before and at the end of study whereas the sciatic function index (SFI), paw withdrawal threshold intensity (PWTI), and paw withdrawal latency (PWL) were assessed every 3 days until the end of study. At the end of study, the determination of nerve conduction velocity (NCV), axon density, oxidative stress status, and aldose reductase (AR) activity of the lesion nerve were performed. It was found that PWCG improved SFI, PWTI, PWL, and NCV together with the improved oxidative stress status and the axon density in the lesion nerve. No changes of AR activity or blood sugar level were observed. Therefore, PWCG might improve the functional and structural changes in STZ-diabetic rats plus CCI via the improved oxidative stress status.