Probiotic Bifidobacterium breve MCC1274 Mitigates Alzheimer’s Disease-Related Pathologies in Wild-Type Mice

Probiotics improve brain function, including memory and cognition, via the microbiome–gut–brain axis. Oral administration of Bifidobacterium breve MCC1274 (B. breve MCC1274) improves cognitive function in App^NL-G-F mice and mild cognitive impairment (MCI) subjects, and mitigates Alzheimer’s disease (AD)-like pathologies. However, its effects on wild-type (WT) mice have not yet been explored. Thus, the effects of B. breve MCC1274 on AD-like pathologies in two-month-old WT mice were investigated, which were orally administered B. breve MCC1274 for four months. Aβ levels, amyloid precursor protein (APP), APP processing enzymes, phosphorylated tau, synaptic protein levels, glial activity, and cell proliferation in the subgranular zone of the dentate gyrus were evaluated. Data analysis was performed using Student’s t-test, and normality was tested using the Shapiro–Wilk test. Oral administration of B. breve MCC1274 in WT mice decreased soluble hippocampal Aβ42 levels by reducing presenilin1 protein levels, and reduced phosphorylated tau levels. It also activated the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, which may be responsible for the reduction in presenilin1 levels and inhibition of tau phosphorylation. B. breve MCC1274 supplementation attenuated microglial activation and elevated synaptic protein levels in the hippocampus. These findings suggest that B. breve MCC1274 may mitigate AD-like pathologies in WT mice by decreasing Aβ42 levels, inhibiting tau phosphorylation, attenuating neuroinflammation, and improving synaptic protein levels.     

The Neuroprotection of Verbascoside in Alzheimer’s Disease Mediated through Mitigation of Neuroinflammation via Blocking NF-κB-p65 Signaling

Verbascoside (VB) is a phenylethanoid glycoside extracted from the herbaceous plant Verbascum sinuatum and plays a neuroprotective role in Alzheimer’s disease (AD). The goal of this study was to explore the neuroprotective mechanism of VB. Based on the proteomics analysis, immunohistochemistry, immunofluorescence, Western blot, and ELISA were utilized to explore the neuroprotective mechanism of VB in context of neuroinflammation in APP/PS1 mice, LPS-induced BV2 cells, and/or Aβ_1-42-stimulated N2a cells. Proteomic analysis demonstrated that the neuroprotection of VB correlated closely to its anti-inflammatory effect. VB significantly blocked microglia and astrocyte against activation in brains of APP/PS1 mice, suppressed the generation of IL-1β as well as IL-6, and boosted that of IL-4, IL-10 and TGF-β in vivo, which were analogous to results acquired in vitro. Furthermore, VB effectively restrained the phosphorylation of IKKα+β, IκBα, and NF-κB-p65 in APP/PS1 mice; LPS-induced BV2 cells, and Aβ_1-42-stimulated N2a cells and lowered the tendency of NF-κB-p65 translocation towards nucleus in vitro. These results demonstrate that the neuroprotective effect of VB correlates to the modulation of neuroinflammation via NF-κB-p65 pathway, making VB as a hopeful candidate drug for the prevention and treatment of AD.     

Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular amyloid-beta peptide (Aβ) and intracellular neurofibrillar tangles, associated with loss of neurons in the brain and consequent learning and memory deficits. Aβ is the major component of the senile plaques and is believed to play a central role in the development and progress of AD both in oligomer and fibril forms. Inhibition of the formation of Aβ fibrils as well as the destabilization of preformed Aβ in the Central Nervous System (CNS) would be an attractive therapeutic target for the treatment of AD. Moreover, a large number of studies indicate that oxidative stress and mitochondrial dysfunction may play an important role in AD and their suppression or reduction via antioxidant use could be a promising preventive or therapeutic intervention for AD patients. Many antioxidant compounds have been demonstrated to protect the brain from Aβ neurotoxicity. Ferulic acid (FA) is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger. Here we present the role of FA as inhibitor or disaggregating agent of amyloid structures as well as its effects on biological models.     

Protective effects of Acanthopanax divaricatus extract in mouse models of Alzheimer's disease

BACKGROUND

Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity.

MATERIALS/METHODS

We investigated the effects of ADA extract on two mouse models of Alzheimer''s disease (AD); intracerebroventricular injection of β-amyloid peptide (Aβ) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice.

RESULTS

Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Aβ1-42 until evaluation) effectively blocked Aβ1-42-induced impairment in passive avoidance performance, and Aβ1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1α in the hippocampus. In addition, it alleviated the Aβ1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1β in the brain.

CONCLUSIONS

The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD.     

Walnut Oil Reduces Aβ Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease

(1) Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ_1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ_1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.     

Integrative Metabolomic Characterization Reveals the Mediating Effect of Bifidobacterium breve on Amino Acid Metabolism in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is commonly accompanied by global alterations in metabolic profiles, resulting in cognitive impairment and neuroinflammation in the brain. Using ultraperformance liquid chromatography-mass spectrometry, we performed integrative untargeted metabolomic analysis of metabolite alterations in the serum and hippocampal tissues of amyloid-β (Aβ)-injected AD model mice and sham controls. Multivariate analysis revealed that a Bifidobacterium breve CCFM1025 intervention significantly restored the differential metabolites induced by Aβ-injection, resulting in B. breve CCFM1025 serum and hippocampal metabolomes clustering between control and model mice. Furthermore, pathway and metabolite set enrichment analysis found that these altered metabolites were predominantly linked to amino acid metabolism. Overall, the integrative metabolome analysis indicated that B. breve CCFM1025 supplementation could modulate serum and hippocampal metabolomes in the early stage of AD, with amino acids as a potential driver.     

Dietary Spray-Dried Porcine Plasma Reduces Neuropathological Alzheimer’s Disease Hallmarks in SAMP8 Mice

Alzheimer’s disease (AD) is characterized by the aberrant processing of amyloid precursor protein (APP) and the accumulation of hyperphosphorylated tau, both of which are accompanied by neuroinflammation. Dietary supplementation with spray-dried porcine plasma (SDP) has anti-inflammatory effects in inflammation models. We investigated whether dietary supplementation with SDP prevents the neuropathological features of AD. The experiments were performed in 2- and 6-month-old SAMP8 mice fed a control diet, or a diet supplemented with 8% SDP, for 4 months. AD brain molecular markers were determined by Western blot and real-time PCR. Senescent mice showed reduced levels of p-GSK3β (Ser9) and an increase in p-CDK5, p-tau (Ser396), sAPPβ, and the concentration of Aβ_40, (all p < 0.05). SDP prevented these effects of aging and reduced Bace1 levels (all p < 0.05). Senescence increased the expression of Mme1 and Ide1 and pro-inflammatory cytokines (Il-17 and Il-18; all p < 0.05); these changes were prevented by SDP supplementation. Moreover, SDP increased Tgf-β expression (p < 0.05). Furthermore, in aged mice, the gene expression levels of the microglial activation markers Trem2, Ym1, and Arg1 were increased, and SDP prevented these increases (all p < 0.05). Thus, dietary SDP might delay AD onset by reducing its hallmarks in senescent mice.     

Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model

BACKGROUND/OBJECTIVES

Alzheimer''s disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide (Aβ) and oxidative stress in the brain are the most common causes of AD.

MATERIALS/METHODS

Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an Aβ_25-35-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress.

RESULTS

In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the Aβ_25-35-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the Aβ_25-35-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day.

CONCLUSIONS

The present results suggest that CA improves Aβ_25-35-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.     

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [¹⁸F] ([¹⁸F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.     

Efficacy and Safety of Sesame Oil Cake Extract on Memory Function Improvement: A 12-Week,Randomized, Double-Blind,Placebo-Controlled Pilot Study

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer’s disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid β (Aβ) proteins and urine 8-OHdG (8-hydroxy-2′-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p < 0.05). Furthermore, plasma amyloid-β (1–40) and amyloid-β (1–42) levels in the SOCE group decreased significantly compared to that in the placebo group (p < 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p > 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma β-amyloid levels of older adults with memory impairment.     

(-)-Oleocanthal Nutraceuticals for Alzheimer’s Disease Amyloid Pathology: Novel Oral Formulations,Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model

Alzheimer’s disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aβ-amyloid (Aβ) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(–)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of β-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (ScEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aβ plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.     

Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer’s Disease-Related Pathways in the SH-SY5Y Neural Cell Line

Here, we present the first in silico and in vitro evidence of Aβ-like peptides released from meaningful members of the gut microbiome (mostly from the Clostridiales order). Two peptides with high homology to the human Aβ peptide domain were synthesized and tested in vitro in a neuron cell-line model. Gene expression profile analysis showed that one of them induced whole gene pathways related to AD, opening the way to translational approaches to assess whether gut microbiota-derived peptides might be implicated in the neurodegenerative processes related to AD. This exploratory work opens the path to new approaches for understanding the relationship between the gut microbiome and the triggering of potential molecular events leading to AD. As microbiota can be modified using diet, tools for precise nutritional intervention or targeted microbiota modification in animal models might help us to understand the individual roles of gut bacteria releasing Aβ-like peptides and therefore their contribution to this progressive disease.     

Antioxidant and Anti-Inflammatory Properties of Rubber Seed Oil in Lipopolysaccharide-Induced RAW 267.4 Macrophages

Rubber seed oil (RSO) is a typical PUFA-enriched plant oil, but it has not been widely used as a healthy edible oil resource due to the lack of understanding of its nutritional values, health biological effects, and action mechanisms. This work was conducted to characterize the basic physicochemical properties, evaluate the antioxidant and anti-inflammatory properties, and explore the involved mechanisms of RSO in LPS-induced RAW 264.7 cells. In the present study, the basic physicochemical parameters of RSO indicated that RSO has good qualities as a potential edible plant oil resource. In LPS-induced macrophages, RSO supplementation displayed a significant antioxidant effect by decreasing ROS and MDA levels as well as elevating T-AOC. In addition, RSO supplementation showed an anti-inflammatory effect by reducing the production of NO, IL-1β, IL-6, and TNF-α while promoting the production of IL-10. Moreover, RSO supplementation decreased the mRNA expression of IL-6, IL-1β, TNF-α, iNOS, and MCP-1 genes while increasing the mRNA expression of the IL-10 gene. Furthermore, RSO supplementation increased Nrf2 protein expression and up-regulated antioxidant genes (HO-1 and NQO-1), which was accompanied by the decrease in TLR4 protein expression and NF-κB p65 phosphorylation as well as IκBα phosphorylation. This study provided some insight into the applications of RSO as a healthy edible oil resource.     

Dietary Glycemic Load and Plasma Amyloid-β Biomarkers of Alzheimer’s Disease

Previous studies have highlighted links between a high-glycemic-load (GL) diet and Alzheimer’s disease in apolipoprotein E ε4 (APOE4) carriers. However, the impact of high-GL diet on plasma amyloid-β (Aβ), an Alzheimer’s disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aβ peptides (Aβ₄₀, Aβ₄₂ concentration and Aβ₄₂/Aβ₄₀ ratio) and GL. The influence of the GL of four meal types (breakfast, lunch, afternoon snack, and dinner) was also determined. From the prospective Three-City study, 377 participants with plasma Aβ measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aβ and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aβ₄₂ concentration (β = −2.2 [CI = −4.27, −0.12], p = 0.038) and lower Aβ₄₂/Aβ₄₀ ratio (β = −0.009 [CI = −0.0172, −0.0007], p = 0.034) in the model adjusted for center, age, sex, education level, APOE4 status, energy intake, serum creatinine, total cholesterol, and Mediterranean-like diet. No significant association was found with the GL of the other meal types. These results suggest that dietary GL may independently modulate the plasma Aβ of the APOE4 status. The mechanism underlying diet, metabolic response, and Aβ peptide regulation must be elucidated.     

Upregulation of Vitamin C Transporter Functional Expression in 5xFAD Mouse Intestine

The process of obtaining ascorbic acid (AA) via intestinal absorption and blood circulation is carrier-mediated utilizing the AA transporters SVCT1 and SVCT2, which are expressed in the intestine and brain (SVCT2 in abundance). AA concentration is decreased in Alzheimer’s disease (AD), but information regarding the status of intestinal AA uptake in the AD is still lacking. We aimed here to understand how AA homeostasis is modulated in a transgenic mouse model (5xFAD) of AD. AA levels in serum from 5xFAD mice were markedly lower than controls. Expression of oxidative stress response genes (glutathione peroxidase 1 (GPX1) and superoxide dismutase 1 (SOD1)) were significantly increased in AD mice jejunum, and this increase was mitigated by AA supplementation. Uptake of AA in the jejunum was upregulated. This increased AA transport was caused by a marked increase in SVCT1 and SVCT2 protein, mRNA, and heterogeneous nuclear RNA (hnRNA) expression. A significant increase in the expression of HNF1α and specific protein 1 (Sp1), which drive SLC23A1 and SLC23A2 promoter activity, respectively, was observed. Expression of hSVCT interacting proteins GRHPR and CLSTN3 were also increased. SVCT2 protein and mRNA expression in the hippocampus of 5xFAD mice was not altered. Together, these investigations reveal adaptive up-regulation of intestinal AA uptake in the 5xFAD mouse model.     

Vitamin E status of 20- to 59-year-old adults living in the Seoul metropolitan area of South Korea

BACKGROUND/OBJECTIVES

Vitamin E is a fat-soluble vitamin and functions primarily as a lipid antioxidant. Inadequate vitamin E status may increase risk of several chronic diseases. Thus, the objectives of this study were to estimate intake and plasma concentration of each tocopherol and to evaluate vitamin E status of Korean adults.

SUBJECTS/METHODS

Three consecutive 24-h food recalls and fasting blood samples were collected from healthy 20- to 59-y-old adults (33 males and 73 females) living in the Seoul metropolitan area, South Korea. α-, β-, δ-, and γ-tocopherol intakes and plasma concentrations of tocopherols (α-, δ-, and γ-tocopherol) were analyzed by gender.

RESULTS

Dietary vitamin E and total vitamin E intake (dietary plus supplemental vitamin E) was 17.68 ± 14.34 and 19.55 ± 15.78 mg α-tocopherol equivalents, respectively. The mean daily α-tocopherol, and γ-tocopherol intakes were 3.07 ± 2.27 mg and 5.98 ± 3.74 mg, respectively. Intakes of total vitamin E and each tocopherol of males were significantly higher than those of females (P < 0.05). Plasma α-tocopherol concentration was 15.45 ± 10.16 of males and 15.00 ± 4.54 µmol/L of females, respectively. There were no significant differences in plasma tocopherol concentrations by gender (P ≥ 0.05). Plasma α-tocopherol was negatively correlated with γ-tocopherol intake (P < 0.05). Twenty-three percent of the subjects had plasma α-tocopherol concentrations < 12 µmol/L indicating a biochemical deficiency of vitamin E. Approximately 8% and 9% of these participants had plasma α-tocopherol:total lipid ratio less than 1.59 µmol/mmol and plasma α-tocopherol:total cholesterol ratio less than 2.22 µmol/mmol, respectively, which are also indicative of vitamin E deficiency.

CONCLUSIONS

Vitamin E intakes of Korean adults were generally adequate with the Korean Dietary Reference Intakes for vitamin E. However, α-tocopherol intake was lower than that reported in other countries, and 23% of the subjects in the current study were vitamin E deficient based on plasma α-tocopherol concentrations.     

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta25–35-induced Alzheimer's disease mouse model

BACKGROUND/OBJECTIVESAlzheimer''s disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD.MATERIALS/METHODSWe orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ_25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues.RESULTSPT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress.CONCLUSIONSOur study demonstrated that administration of PT improved Aβ_25–35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.