Anxiolytic, Antidepression, and Memory-Enhancing Effects of the Novel Instant Soup RJ6601 in the Middle-Aged of Female Rats.

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-1ß, 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.

Omega-3-Rich Tuna Oil Derived from By-Products of the Canned Tuna Industry Enhances Memory in an Ovariectomized Rat Model of Menopause.

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.

Positive effects of anthocyanin-rich mulberry milk on mental health problems in the working population: an open-label study.

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.

A Functional Drink Containing Kaempferia parviflora Extract Increases Cardiorespiratory Fitness and Physical Flexibility in Adult Volunteers.

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 VO2 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.

The Polyherbal Functional Ingredient Containing Ginger, Chinese Date, and Wood Ear Mushroom Protects against Dementia following Metabolic Syndrome.

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.

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.

Cardiovascular complications are resolved by tuna protein hydrolysate supplementation in rats fed with a high-fat diet.

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.

Microbiota-gut-brain axis impairment in the pathogenesis of stroke: implication as a potent therapeutic target.

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.

The potential role of the novel orodispersible film from rice polymer loaded with silkworm pupae hydrolysate and the combined extract of holy basil and ginger for the management of stroke with stress.

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.

Anxiety, Insomnia, and Memory Impairment in Metabolic Syndrome Rats Are Alleviated by the Novel Functional Ingredients from Anacardium occidentale.

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.

Memory-Enhancing Effect of 8-Week Consumption of the Quercetin-Enriched Culinary Herbs-Derived Functional Ingredients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

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.

Corrigendum to "Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat".

[This corrects the article DOI: 10.1155/2011/429505.].

Multiple Bioactivities of Manihot esculenta Leaves: UV Filter, Anti-Oxidation, Anti-Melanogenesis, Collagen Synthesis Enhancement, and Anti-Adipogenesis.

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.

Seed extract of Thai Mucuna pruriens (L.) DC. var. pruriens enhances sexual performance and improves male reproductive damages in ethanol-induced rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Thai Mucuna pruriens (L.) DC. var. pruriens (T-MP) has been traditionally used in treating depressive disorders, dysuria and enhancing male sexual desire. Although T-MP seed is demonstrated to have antioxidant capacity, its aphrodisiac and protective tissue damage properties have never been documented. Recently, ethanol (Eth) is known to cause sexual behavior dysfunction and damage reproductive system. This study aimed to investigate the protective effects of T-MP seed extract on sexual behavior dysfunction and reproductive damages in male rats admisted with Eth. MATERIALS AND METHODS: T-MP possessing antioxidant activity was determined for L-DOPA content using NMR analysis. Thirty-six male rats were divided into four groups (9 animals/group). Control rats received DW and the ethanol (Eth) group was given with Eth (3 g/kgBW; 40%v/v). In preventive groups (T-MP150 + Eth and MP300 + Eth groups), animals were treated with T-MP extract at a dose of 150 and 300 mg/kgBW before Eth administration for consecutive 56 days. Sexual behaviors including mounting frequency (MF), intromission frequency (IF), mounting latency (ML), intromission latency (IL), ejaculation latency (EL), post-ejaculatory interval (PEI), and ejaculation frequency (EF) were evaluated. Epididymal sperm quality and daily sperm production (DSP) were examined. Testicular histology was observed using Masson's trichrome staining. The malondialdehyde (MDA) levels and expressions of androgen receptor (AR), heat shock protein 70 (HSP70), steroidogenic acute regulatory (StAR), and tyrosine-phosphorylated (TyrPho) proteins in testis were also determined. RESULTS: T-MP extract contained L-DOPA and improved sexual behaviors including increased MF and IF and decreased ML and IL in Eth treated rats. Significantly, sperm quality, DSP, and testicular histopathology observed in Eth group were improved after T-MP treatment. T-MP also decreased the testicular MDA levels. Additionally, T-MP could correct testicular functional proteins of AR and StAR except HSP70 expression in Eth group. Expressions of TyrPho proteins in testicular and sperm lysates were improved in co-administered groups. CONCLUSIONS: T-MP seed extract possessing L-DOPA could enhance the sexual behaviors and protect reproductive damages via improvement of testicular functional proteins.

Impact of Pineapple Juice on Expression of CYP3A4, NAT2, SULT1A1 and OATP1B1 mRNA in HepG2 Cells.

<b>Background and Objective:</b> Pineapple (<i>Ananas comosus</i>) is a popular fruit worldwide with natural antioxidant properties. This study examined how pineapple modified the expression of drug-metabolizing enzymes (CYP1A2, CYP2C9, CYP3A4, UGT1A6, NAT2 and SULT1A1) and a drug transporter (OATP1B1) in human hepatocarcinoma (HepG2) cells. <b>Materials and Methods:</b> HepG2 cells (2.5×10⁵ cells/well in a 24-well plate) were incubated with pineapple juice extract (125-1,000 µg mL¹) for 48 hrs in phenol red-free medium. Resazurin reduction, ROS, AST and ALT assays were performed. The mRNA expression of target genes was determined by RT/qPCR. <b>Results:</b> Pineapple juice slightly reduced HepG2 cell viability to 80% of the control, while ROS, AST and ALT levels were not changed. Pineapple juice did not alter the expression of CYP1A2, CYP2C9 and UGT1A6 mRNA. All tested concentrations of pineapple juice suppressed CYP3A4, NAT2 and OATP1B1 expression, while SULT1A1 expression was induced. <b>Conclusion:</b> Though pineapple juice slightly decreased the viability of HepG2 cells, cell morphology and cell function remained normal. Pineapple juice disturbed the expression of phase I (CYP3A4) and phase II (NAT2 and SULT1A1) metabolizing genes and the drug transporter OATP1B1. Therefore, the consumption of excessive amounts of pineapple juice poses a risk for drug interactions.

Neuroprotective Effect of Polyherbal Recipe Containing Ginger, Chinese Date, and Wood Ear Mushroom against Ischemic Stroke with Metabolic Syndrome Condition via Epigenetic Modification of Inflammation and Oxidative Stress.

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.

The Positive Modulation Effect of a 6-Week Consumption of an Anthocyanin-Rich Mulberry Milk on Working Memory, Cholinergic, and Monoaminergic Functions in Healthy Working-Age Adults.

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.

Integrated molecular network and HPLC-UV-FLD analysis to explore antioxidant ingredients in camellia nitidissima Chi.

At present, screening of active ingredients from natural products for pharmacological and clinical research is mostly time-consuming and costly. In this study, a molecular network (MN) guided high performance liquid chromatography-ultraviolet-fluorescence detector (HPLC-UV-FLD) method was carried out to profile the global antioxidant activity compounds, including the trace amount ingredients in Camellia nitidissima Chi (CNC). Firstly, HPLC-UV-FLD postcolumn derivatization system was utilized to screen the antioxidants. Then the MN of CNC was established via mass spectrometry (MS) data for getting the connection between ingredient structures. As a result, HPLC-UV-FLD indicated three antioxidant ingredients: gallic acid (126.3 mg/g), catechin (564.8 mg/g), and salicylic acid (24.3 mg/g). Combined with the MN, the actives' precise location and connection relationship were clarified based on the structural similarities. A new antioxidant ingredient, okicamelliaside, was suggested and evaluated at free radical scavenging and enzymatic protection. The novel method of activity and structural correlation analysis based on MN could provide a useful guide for screening trace active ingredients in natural products. PRACTICAL APPLICATION: Three main ingredients were screened out from Camellia nitidissima Chi by HPLC-UV-FLD postcolumn derivatization system. Integrated molecular network and HPLC-UV-FLD analysis, a new type of antioxidant okicamelliaside was selected. The novel method of activity and structural correlation analysis based on molecular network could provide a useful guide for screening trace active ingredients in natural products.

Impact of Pineapple on Mitochondrial Permeability Transition and Drug Metabolizing Genes in Caco-2 Cells.

<b>Background and Objective:</b> Pineapple (<i>Ananas comosus</i> L.) has antioxidant and other pharmacological properties. This study examined how pineapple modified mitochondrial permeability transition and expression of drug-metabolizing enzymes, i.e., CYP1A2, CYP2C9, CYP3A4, UGT1A6, NAT2 and the drug transporter OATP1B1 in human colorectal adenocarcinoma (Caco-2) cells. <b>Materials and Methods:</b> Caco-2 cells (2.5×10⁵ cells well¹ in 24-well plates) were incubated with pineapple (125 to 1,000 µg mL¹) for 48 hrs in a phenol red-free medium. Mitochondrial permeability transition, resazurin cell viability and AST and ALT levels were investigated. The mRNA expression of target genes was determined by RT/qPCR. <b>Results:</b> Pineapple significantly reduced depolarized mitochondria, slightly decreased cell viability and did not change AST and ALT levels. Pineapple did not modify the mRNA expressions of CYP1A2, CYP2C9 and CYP3A4 but markedly induced UGT1A6 expression. The highest tested concentration of pineapple (1,000 µg mL¹) significantly suppressed NAT2 and OATP1B1 expression. <b>Conclusion:</b> Although pineapple slightly decreased cell viability to ~80% of control, the morphology and functions of the cells were unaffected. Pineapple showed a beneficial effect to reduce depolarized mitochondria, which consequently decreased reactive oxygen species production. Pineapple did not modify the expression of CYPs, whilst it altered the expression of phase 2 metabolizing genes UGT1A6 and NAT2 and the transporter OATP1B1. Therefore, the consumption of large amounts of pineapple is of concern for the risk of drug interaction via alteration of UGT1A6, NAT2 and OATP1B1 expression.

Memory-Enhancing Effect of a Phytosome Containing the Combined Extract of Mulberry Fruit and Ginger in an Animal Model of Ischemic Stroke with Metabolic Syndrome.

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.