Search Results (91)

Sleep deprivation (SD) induces cognitive impairment associated with gut microbiota dysbiosis, making it crucial to explore natural remedies targeting the microbiota–gut–brain axis. This study aims to investigate whether Ficus pandurata var. angustifolia W.C. Cheng (a traditional medicine–food plant rich in flavonoids) can mitigate cognitive impairment caused by SD by modulating the gut microbiota. The sleep-deprived mouse model was established using the multiple platform water environment method. This study investigated the effects of F. pandurata var. angustifolia flavonoids (FCFs) via behavioral tests, 16S rRNA sequencing, and biochemical analyses to assess cognitive function, gut microbiota, and related pathways. FCF alleviated SD-induced cognitive deficits, reversed gut microbiota dysbiosis (increased beneficial bacteria like Lactobacillus, reduced harmful ones like Desulfovibrio), promoted short-chain fatty acids production, improved colonic histopathology and intestinal barrier function, reduced serum lipopolysaccharide, inhibited glial cell activation and TLR4/NF-κB signaling, and regulated neurotransmitters. In conclusion, FCF ameliorates SD-induced cognitive impairment through regulating gut microbiota, enhancing intestinal barrier, and suppressing neuroinflammation via the microbiota–gut–brain axis, providing a theoretical basis for its application. Full article

Background/Objectives: The hippocampus is an essential part of the central nervous system (CNS); it plays a significant role in social–cognitive memory processing. Prenatal exposure to valproic acid (VPA) can lead to impaired hippocampal functions. In this study, we evaluated the effect of plumbagin (PLB) as a natural product on spatial learning and memory, neuro-morphological changes, and inflammation levels in a VPA-induced autism model during adolescence. Methods: Pregnant Wistar rats received a single intraperitoneal (i.p.) injection of VPA (600 mg/kg) or saline on gestational day 12.5. The male offspring were then categorized and assigned to five groups: Saline+DMSO-, VPA+DMSO-, and VPA+PLB-treated groups at doses of 0.25, 0.5, or 1 mg/kg. Spatial learning and memory were evaluated using the Morris water maze. Histopathological evaluations of the hippocampus were performed using Nissl and hematoxylin–eosin staining, as well as immunofluorescence. The pro-inflammatory cytokine levels were also quantified by quantitative real-time PCR. Results: The findings revealed that a VPA injection on gestational day 12.5 is associated with cognitive impairments in male pups, including a longer escape latency and traveled distance, as well as decreased time spent in the target quadrant. Treatment with PLB significantly enhanced the cognitive function, reduced dark cells, and ameliorated neuronal–morphological alterations in the hippocampus of VPA-exposed rats. Moreover, PLB was found to reduce astrocyte activation and the expression levels of pro-inflammatory cytokines. Conclusions: These findings suggest that PLB partly mitigates VPA-induced cognitive deficits by ameliorating hippocampal inflammation levels. Full article

Radiation exposure causes neuroinflammation, oxidative stress, and neuronal loss, leading to cognitive and behavioral impairments. This study aims to evaluate the effect of niacin interventions on whole-brain irradiation (WBI)-induced cognitive and behavioral impairment. Female Wistar rats were randomly assigned to Control (Group 1), Radiation +Saline (Group 2), and Radiation +niacin (Group 3) groups. Rats in the irradiated groups (Groups 2 and 3) received a single dose of 20 Gy photon irradiation. Group 2 received water seven days after irradiation, while Group 3 received niacin (60 mg/kg, 2 mL) oral gavage for 15 days. On days 22, 23, and 24, behavioral assessments were performed, including the Open Field Test, the Sociability Test, and the Passive Avoidance Learning (PAL) task. Biochemical analyses included MDA, BDNF, TNF-α, CREB), SIRT1, and SIRT6 measured by ELISA. Histological assessments included neuronal density and GFAP immunostaining in CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons. Radiation exposure importantly increased MDA and TNF-α levels, while SIRT1, SIRT6, BDNF, and CREB were notably reduced. This was accompanied by neuronal loss in the cerebellum and hippocampus, astrogliosis, and behavioral and cognitive deficits. Niacin treatment significantly decreased MDA and TNF-α levels while increasing BDNF, CREB, SIRT1, and SIRT6 expression, attenuating neuronal apoptosis. Immunohistochemical analysis demonstrated that niacin treatment enhanced neuronal density in the CA1 and CA3 regions of the hippocampus and cerebellar Purkinje neurons while reducing GFAP immunoreactivity in the CA1, CA3, and cerebellum following WBI. Behaviorally, niacin treatment improved social interaction, locomotor activity, and memory performance, underscoring its neuroprotective potential against WBI-induced damage. These findings suggest that niacin may ameliorate behavioral and cognitive impairments following whole brain irradiation by activating the SIRT1/CREB/BDNF or SIRT1/SIRT6/MDA/TNF-α signaling pathway. Full article

Background: Alzheimer’s disease (AD) is the most common dementia, characterized by significant cognitive impairments and neural network dysfunction. Currently, multiple therapeutic strategies are being developed to design effective anti-AD drugs. Among them, Withaferin A (WA), a natural steroidal lactone extracted from Withania somnifera leaves, has been shown to reduce amyloid-β (Aβ) peptide levels in vitro. However, its potential to improve cognitive function in AD remains unclear. Methods: In this study, 5xFAD mice were administered WA (2 mg/kg intraperitoneally every 2 days) for 14 days, and its neuroprotective effects were evaluated through behavioral tests, wide-field imaging, immunohistochemistry, and ELISA. Results: WA significantly improved short-term memory, as evidenced by enhanced performance in the Novel Object Recognition Test (NORT) (p < 0.001, n = 10), Novel Location Recognition Test (NLRT) (p < 0.01, n = 14), and Three-Chamber Social Test (TCST) (p < 0.001, n = 8). WA also ameliorated long-term memory deficits in the Morris Water Maze Test (MWMT) (p < 0.05, n = 7). Furthermore, cortical wide-field Ca²⁺ imaging revealed that WA treatment rescued slow-wave impairments by enhancing long-range coherence (0.8363 ± 0.0185, p < 0.01, n = 8) and reducing the frequency of slow-wave activity (0.6578 ± 0.0512 Hz, p < 0.01, n = 8). Additionally, WA treatment significantly reduced Aβ plaque deposition in both cortical and hippocampal regions. Conclusions: These findings suggest that WA may be a promising therapeutic agent for AD, exerting neuroprotective effects. Full article

Memory impairment is a defining characteristic of Alzheimer’s disease (AD), with amnesia often appearing as its earliest symptom. Given the multifactorial nature of AD pathogenesis, this study investigates the multi-target therapeutic potential of sobrerol (coded as NRM-331) in a scopolamine-induced amnesia mouse model, focusing specifically on its effects in ameliorating memory deficits and enhancing neuronal plasticity. Sixty male C57BL/6NCrljOri mice were divided into six groups (10 mice/group): vehicle control (CTL, saline), scopolamine (SPA, 10 mg/kg/day), Aricept (APT, 2 mg/kg/day), and three treatment groups receiving NRM-331 at doses of 40, 80, and 100 mg/kg/day. Several behavioral tests were conducted, including the Y-maze test, passive avoidance test, and Morris water maze test. Additionally, biochemical assays were performed in serum (to measure Aß 1-40 and Aß 1-42) and in the brain (to assess ACh and AChE levels), along with histopathological examination of the brain using Nissl staining and p-tau IHC. No significant change was observed in the Y-maze test or the acquisition trial of the passive avoidance test. However, improvements were noted in the retention trial of the passive avoidance test and the Morris water maze test (including escape latency, swim distance, and number of platform crossed) for the NRM-331 groups compared to the SPA group. Serum levels of Aß 1-40 and Aß 1-42 decreased in the NRM-331 groups compared to the SPA group. In the brain, levels of ACh significantly increased, while AChE levels significantly decreased compared to the SPA group. The number of neuronal cells improved in the CA1, CA3, and DG regions of the hippocampus, as indicated by Nissl staining. A significant reduction in p-tau accumulation was also observed in the NRM-331 groups. In conclusion, NRM-331 demonstrated an anti-amnesic effect by enhancing hippocampal cholinergic signaling, alongside exhibiting anti-tau and anti-Aβ synthesis properties. These therapeutic effects suggest that NRM-331 significantly mitigates memory impairment induced by SPA through a neuroprotective mechanism. Full article

Background/Objectives: Brain insulin resistance is a potential causal factor for dementia in Alzheimer’s disease (AD). Insulin-like growth factor-1 (IGF-1), a neurotrophin, plays a key role in central insulin signaling and neuroprotection. Intracerebrovenitricular (ICV) administration of streptozotocin (STZ) disrupts insulin signal transduction, leading to brain insulin resistance, which may mimic the early pathophysiological changes in sporadic AD (sAD). In this study, we investigated whether restoring insulin signaling through ICV injection of IGF-1 could ameliorate spatial memory deficits during sAD progression in a rat model induced by ICV STZ injection. Methods: Male Wistar rats (n = 40) were subjected to double ICV injections of STZ (0.75 mg/kg/ventricle, days 2 and 4) and IGF-1 (1 μg/single injection, days 1 and 3), and placed at the Morris water maze (MWM) at baseline, 7, 45 and 90 days after injections. Reference (days 1–3 and day 4 MWM)) and working (days 5–8 MWM) memory, microglia activation (CD68⁺ cells), and amyloid β (Aβ) deposition (immunohistochemistry) were measured. Results: We found that ICVIGF-1 administration protected working memory demonstrated as (1) reduced latency to reach the platform, and reduced swimming distance in trials 3 (p < 0.05) and 4 (p < 0.01) on days 45 and 90 post-injection and (2) a short-term (up to 45 days post-injection) enhancement of reference memory, manifested by a reduction in swimming distance and latency (p < 0.05). Furthermore, IGF-1 treatment reduced neuroinflammation in CA2 (p < 0.05) and Aβ deposition in CA1(p < 0.01) of the hippocampus. Conclusions: Central IGF-1 attenuates spatial memory deficits in the ICVSTZ-induced sAD model by reducing neuroinflammation and Aβ accumulation in the hippocampus. Full article

Weizmannia coagulans BC99, a Gram-positive, spore-forming, lactic acid-producing bacterium is renowned for its resilience and health-promoting properties, W. coagulans BC99 survives harsh environments, including high temperatures and gastric acidity, enabling effective delivery to the intestines. The consequences of chronic sleep deprivation (SD) include memory deficits and gastrointestinal dysfunction. In this study, a chronic sleep deprivation cognitive impairment model was established by using a sleep deprivation instrument and W. coagulans BC99 was given by gavage for 4 weeks to explore the mechanism by which BC99 improves cognitive impairment in sleep-deprived mice. BC99 improved cognitive abnormalities in novel object recognition tests induced by chronic sleep deprivation and showed behavior related to spatial memory in the Morris water maze test. W. coagulans BC99 reduced the heart mass index of sleep-deprived mice, increased the sleep-related neurotransmitters 5-HT and DA, decreased corticosterone and norepinephrine, and increased alpha diversity and community similarity. It reduced the abundance of harmful bacteria such as Olsenella, increased the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium, and promoted the production of short-chain fatty acids (SCFAs). W. coagulans BC99 also inhibits LPS translocation and the elevation of peripheral inflammatory factors by maintaining the integrity of the intestinal barrier and inhibiting the expression of the NLRP3 signaling pathway in the jejunum, thereby inhibiting the NLRP3 inflammasome in the brain of mice and reducing inflammatory factors in the brain, providing a favorable environment for the recovery of cognitive function. The present study confirmed that W. coagulans BC99 ameliorated cognitive impairment in chronic sleep-deprived mice by improving gut microbiota, especially by promoting SCFAs production and inhibiting the NLRP3 signaling pathway in the jejunum and brain. These findings may help guide the treatment of insomnia or other sleep disorders through dietary strategies. Full article

Plants face various stresses, particularly water deficit, which negatively impacts photosynthesis, growth, and development, thereby limiting agricultural production. Utilizing growth regulators, such as amino acids and polyamines, to enhance osmotic stress tolerance is a crucial area of research in sustainable agriculture. This study investigates the impact of arginine and spermine treatments on various growth attributes, enzymatic and non-enzymatic antioxidants, photosynthetic pigments, protein and lipid peroxidation, and yield traits of fenugreek plants under both normal and drought conditions. The results indicate that drought conditions significantly reduce morphological characteristics, leaf pigments, and yield traits. However, the application of arginine and spermine enhances these parameters, with spermine showing a more pronounced effect. Additionally, treatments boost antioxidant enzymes activities and improve the levels of non-enzymatic antioxidants and osmolytes, contributing to better stress tolerance and growth performance. Principal component analysis confirms that drought significantly alters plant physiology, increasing proline and malondialdehyde levels, while arginine and spermine alleviate drought stress by enhancing antioxidant activity and osmolyte accumulation. The current investigation aims to evaluate the effectiveness of spermine and arginine treatments on various growth attributes and stress tolerance of fenugreek plants under normal and drought conditions, focusing on their comparative efficacy. Full article

In many sustainable agricultural systems, combining soil ameliorants with deficit irrigation is a viable strategy. However, little is known about how this approach affects soil quality, crop water productivity (CWP), and sugar beet (Beta vulgaris L.) yield in sandy soils. This study investigates the effects of different soil ameliorants―potassium polyacrylate (PPA), polyacrylamide (PAM), and humus (HA)―on the soil chemical properties, water productivity, and sugar beet yield under three irrigation regimes (100%, 80%, and 50% of crop water requirement (CWR). The results demonstrated that applying these amendments signficantly enhances soil pH, cation exchange capacity (CEC), organic matter (OM), and the availability of essential nutrients (N, P, and K). Notably, the combination of PAM and HA under 50% CWR resulted in the highest improvements in sugar beet biomass, increasing shoot and root growth by 73.43% and 71.68%, respectively. It also led to a 97.91% increase in sugar yield and a 4.22% improvement in sugar quality. However, this treatment had the lowest economic benefit, with a negative outcome. In contrast, PAM treatment under 50% CWR produced a 61.49% increase in sugar yield and a 2.44% improvement in sugar quality, ensuring economic viability. These findings suggest that the use of PAM under reduced irrigation conditions can optimize water use efficiency and sustain crop productivity in sandy soils. Full article

Enhancing global agricultural sustainability critically requires improving the physicochemical properties of saline–alkali soil. Biochar has gained increasing attention as a strategy due to its unique properties. However, its effect on the physicochemical properties of saline–alkali soil varies significantly. This study uses psychometric meta-analysis across 137 studies to synthesize the findings from 1447 relatively independent data sets. This study investigates the effects of biochar with different characteristics on the top 20 cm of various saline–alkali soils. In addition, aggregated boosted tree (ABT) analysis was used to identify the key factors of biochar influencing the physicochemical properties of saline soils. The results showed that biochar application has a positive effect on improving soil properties by reducing the sodium adsorption ratio (SAR) and the exchangeable sodium percentage (ESP) by 30.31% and 28.88%, respectively, with a notable 48.97% enhancement in cation exchange capacity (CEC). A significant inverse relationship was found between soil salinity (SC) and ESP, while other factors were synergistic. Biochar application to mildly saline soil (<0.2%) and moderately saline soil (0.2–0.4%) demonstrated greater improvement in soil bulk density (SBD), total porosity (TP), and soil moisture content (SMC) compared to highly saline soil (>0.4%). However, the reduction in SC in highly saline soil was 4.9 times greater than in moderately saline soils. The enhancement of soil physical properties positively correlated with higher biochar application rates, largely driven by soil movements associated with the migration of soil moisture. Biochar produced at 401–500 °C was generally the most effective in improving the physicochemical properties of various saline–alkali soils. In water surplus regions, for mildly saline soil with pH < 8.5, mixed biochar (pH 6–8) at 41–80 t ha⁻¹ was the most effective in soil improvement. Moreover, in water deficit areas with soil at pH ≥ 8.5, biochar with pH ≤ 6 applied at rates of >80 t ha⁻¹ showed the greatest benefits. Agricultural residue biochar showed superior efficiency in ameliorating highly alkaline (pH ≥ 8.5) soil. In contrast, the use of mixed types of biochar was the most effective in the amelioration of other soil types. Full article

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by β-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut–brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections. Full article

Background/Objectives: Alzheimer’s disease (AD) is an age-related degenerative brain disorder characterized by a progressive decline in cognitive function and memory. This study aimed to evaluate whether rutin hydrate (RH) has neuroprotective effects in an AD-like learning and memory impairment rat model induced by scopolamine (SCO). Methods: The rats were administered with RH (100 mg/kg) and SCO (1.5 mg/kg) and underwent behavioral tests, including the Morris water maze test, Y-maze test, and passive avoidance test, to evaluate their learning and memory abilities. Additionally, long-term potentiation (LTP) was induced to observe changes in the field excitatory postsynaptic potential (fEPSP) activity. Results: RH treatment attenuated the SCO-induced shortening of step-through latency in the passive avoidance (PA) test, increased the percentage of alternation in the Y-maze, and increased the time spent in the target zone in the Morris water maze (MWM). Moreover, RH increased the total activity of fEPSP following theta burst stimulation and attenuated the SCO-induced blockade of fEPSP. RH also ameliorated the SCO-induced decrease in the expression levels of the BDNF, TrkB, ERK, CREB, and Bcl-2 proteins and the increase in the Bax protein level in the rat hippocampus. This demonstrates that RH has beneficial neuroprotective effects in the brain, improving learning, memory, and synaptic plasticity in rats. Conclusions: Our results highlight the molecular and cellular mechanisms through which RH exerts its neuroprotective effects in the prevention and treatment of learning and memory deficit disorders. RH could potentially be used as a therapeutic strategy for the restoration of learning and memory function and the prevention of the progression of AD. Full article

The maintenance of proper brain function relies heavily on the balance of excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor of synapse formation by interfering with Neuroligin-mediated interactions, crucial for maintaining the excitatory–inhibitory (E/I) balance. Mdga1^−/− mice exhibit selectively enhanced inhibitory synapse formation in their hippocampal pyramidal neurons, leading to impaired hippocampal long-term potentiation (LTP) and hippocampus-dependent learning and memory function; however, it has not been fully investigated yet if the reduction in MDGA1 protein levels would alter brain function. Here, we examined the behavioral and synaptic consequences of reduced MDGA1 protein levels in Mdga1^+/− mice. As observed in Mdga1^−/− mice, Mdga1^+/− mice exhibited significant deficits in hippocampus-dependent learning and memory tasks, such as the Morris water maze and contextual fear-conditioning tests, along with a significant deficit in the long-term potentiation (LTP) in hippocampal Schaffer collateral CA1 synapses. The acute administration of D-cycloserine, a co-agonist of NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated memory impairments and restored LTP deficits specifically in Mdga1^+/− mice, while having no such effect on Mdga1^−/− mice. These results highlight the critical role of MDGA1 in regulating inhibitory synapse formation and maintaining the E/I balance for proper cognitive function. These findings may also suggest potential therapeutic strategies targeting the E/I imbalance to alleviate cognitive deficits associated with neuropsychiatric disorders. Full article

The increasing prevalence of age-related neurodegenerative disorders owing to the aging population worldwide poses substantial challenges. This study investigated the neuroprotective effects of protocatechuic acid (PCA), a compound found in various fruits, vegetables, and grains, using a scopolamine-induced hypomnesia mouse model. Six-week-old male C57BL/6J mice were orally administered PCA at doses of 10 and 100 mg/kg body weight per day for two weeks, along with intraperitoneal injections of scopolamine. Learning and memory abilities were assessed using the passive avoidance, Morris water maze, and Y-maze behavioral assays. Biochemical analyses evaluated the levels of oxidative stress markers, including 8-hydroxydeoxyguanosine (8-OHdG) in the blood and malondialdehyde (MDA) in the brain, as well as phase II antioxidant proteins in the hippocampus. Histological examination was conducted to determine hippocampal integrity. Our results demonstrated that PCA administration at 10 mg/kg body weight per day or higher for two weeks (i) significantly ameliorated scopolamine-induced learning and memory impairments, as evidenced by improved performance in behavioral tasks, (ii) reduced plasma 8-OHdG levels and cerebral MDA levels in a dose-dependent manner, (iii) increased antioxidant protein expressions in the hippocampal tissue, and (iv) mitigated histological damage in the hippocampal region of the brain. These findings suggest that oral administration of PCA provides neuroprotective effects against oxidative stress-induced learning and memory impairments, possibly through upregulating antioxidant machinery. Therefore, PCA may serve as a promising dietary supplement for mitigating cognitive deficits associated with neurodegenerative diseases. Full article

The management of invasive plants is a challenge when using traditional control methods, which are ineffective for large areas, leading to the abandonment of invaded areas and the subsequent worsening of the situation. Finding potential uses for waste resulting from invaders’ management could motivate their control in the long-term, concurrently providing new bio-based resources with different applications. Oxalis pes-caprae is an invasive plant, widely distributed worldwide, which spreads aggressively through bulbils, creating a dense ground cover. This study was designed to assess the potential of Oxalis aboveground waste for use as fertilizer and in ameliorating deficit irrigation effects in growing crops. Diplotaxis tenuifolia (wild rocket) seedlings were planted in pots with soil mixed with Oxalis waste at 0, 2.2 and 4.3 kg m⁻² or with commercial fertilizer, left to grow for 27 days and then irrigated at 100% or 50% field capacity for 14 days. The incorporation of the Oxalis waste improved the biomass, photosynthesis, sugars, total phenols and total antioxidant capacity in the crop, achieving commercial fertilization values, as well as increasing the phosphorus in soils. However, Oxalis waste seems not to directly affect plants’ relative water contents. Our results support the use of Oxalis waste as fertilizer, which can encourage the long-term control of this invasive species. Full article