Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice.

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Effects of endogenous DHA milk and exogenous DHA milk on oxidative stress and cognition in SAMP8 mice.

In this study, Senescence Accelerated Mice (SAMP8) were supplemented with exogenous DHA milk, endogenous DHA milk, normal milk, or 0.9 % saline solution. Enzyme-linked immunosorbent assay (ELISA), gas chromatography (GC), ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI MS/MS), and Morris water maze were used to characterize the effects of diet on oxidative stress and cognition in SAMP8 mice. Supplementation endogenous DHA milk or exogenous DHA milk can enhance the antioxidant capacity of mice organs. Endogenous DHA milk increased the superoxide dismutase (SOD) activity of mice brain and serum than normal milk and 0.9 % saline solution (P ≤ 0.05), as well as increased SOD activity of mice liver and glutathione peroxidase (GSH-Px) activity of mice brain than normal milk (P ≤ 0.05). Exogenous DHA milk increased SOD activity of mice brain than normal milk and 0.9 % saline solution, as well as increased SOD activity of mice serum than 0.9 % saline solution (P ≤ 0.05). Several polar lipid relative content, such as 18:0/18:2 PS, 17:0 Ceramide, and 20:4 LPC in mice brain was affected by dietary supplementation with DHA-containing milk. Lipid oxidation metabolites in mice brain were not affected by DHA-containing milk. Endogenous DHA milk increased the number of platform location crossing times of mice in the Morris water maze test, compared with Exogenous DHA milk, normal milk, and 0.9 % saline solution (P ≤ 0.05).

Lancao decoction alleviates cognitive dysfunction: A new therapeutic drug and its therapeutic mechanism.

BACKGROUND: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear. PURPOSE: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice. METHODS: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons. RESULTS: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice. CONCLUSION: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus.

Sesamol ameliorates dextran sulfate sodium-induced depression-like and anxiety-like behaviors in colitis mice: the potential involvement of the gut-brain axis.

Inflammatory bowel disease (IBD) is accompanied by some psychiatric disorders, including anxiety and depression. Sesamol has been reported to alleviate colitis symptoms and depression-like behaviors caused by chronic unpredictable mild stress, but its protective effect and underlying neurobiological mechanism on IBD induced by dextran sulfate sodium (DSS) accompanying depression-like and anxiety-like behaviors remains still unclear. Here, we found that a six-week sesamol treatment (100 mg per kg bodyweight per day) for DSS-induced mice predominantly prevented inflammatory response, epithelial barrier dysfunction and depression-like and anxiety-like behaviors via the gut-brain axis. Sesamol alleviated neuroinflammatory responses via suppressing the TLR-4/NF-κB pathway, protected against oxidative stress and upregulated the Nrf2 antioxidant signaling pathway. Moreover, sesamol treatment improved brain-derived neurotrophic factor (BDNF) by upregulating the BDNF/TrkB/CREB signaling pathway, restored synaptic impairments and enhanced norepinephrine (NE) and serotonin (5-HT) levels. Importantly, the correlation analysis showed that the gut barrier and lipopolysaccharide (LPS) content in the serum were highly associated with behavioral performance and the biochemical indexes of the brain. In summary, the present study indicates that sesamol is a novel nutritional intervention strategy for preventing IBD and its symptoms of anxiety and depression.

A Mixture of Ginkgo biloba L. Leaf and Hericium erinaceus (Bull.) Pers. Fruit Extract Attenuates Scopolamine-Induced Memory Impairments in Mice.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by loss of memory and cognitive impairment via dysfunction of the cholinergic nervous system. In cholinergic dysfunction, it is well known that impaired cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) signaling are major pathological markers and are some of the strategies for the development of AD therapy. Therefore, this study is aimed at evaluating whether a mixture comprising Ginkgo biloba L. leaf (GL) and Hericium erinaceus (Bull.) Pers. (HE) fruit extract (GH mixture) alleviated cognitive impairment induced in a scopolamine-induced model. It was discovered that GH reduced neuronal apoptosis and promoted neuronal survival by activating BDNF signaling in an in vitro assay. In addition, the GH (p.o. 240 mg/kg) oral administration group significantly restored the cognitive deficits of the scopolamine-induced mouse group (i.p. 1.2 mg/kg) in the behavior tests such as Y-maze and novel object recognition task (NORT) tests. This mixture also considerably enhanced cholinergic system function in the mouse brain. Furthermore, GH markedly upregulated the expressed levels of extracellular signal-regulated kinase (ERK), CREB, and BDNF protein levels. These results demonstrated that GH strongly exerted a neuroprotective effect on the scopolamine-induced mouse model, suggesting that an optimized mixture of GL and HE could be used as a good material for developing functional foods to aid in the prevention of neurodegenerative diseases, including AD.

Insights into the neuroprotective effects of Salvia officinalis L. and Salvia microphylla Kunth in the memory impairment rat model.

Salvia species have a longstanding traditional culinary use, mostly being consumed in the Mediterranean diet as a common herb added to food. Salvia is commonly consumed as a herbal tea for memory enhancement. Alzheimer's disease (AD) is the most prevalent form of dementia affecting people worldwide Therefore, the current research aimed to investigate potential therapeutic benefits of Salvia officinalis (SOL) cultivated in Jordan and Salvia microphylla (SML) cultivated in Egypt with regard to acetylcholinesterase activity, ß-amyloid deposition and oxidative stress associated with scopolamine-induced AD. Metabolite profiling of the ethanol extracts of SOL and SML was performed using UPLC-ESI-MS/MS analysis. Methyl carnosate, carnosic acid, carnosol, rosmanol and salvianolic acids were the major secondary metabolites identified in SOL and SML extracts. In our study, scopolamine (1.14 mg kg-1, i.p.) was administered for 7 consecutive days to induce memory impairment in rats. SML and SOL (150 and 300 mg kg-1, p.o.) were tested for their effects to reduce the scopolamine-induced deficits. Donepezil (0.5 mg kg-1, i.p.) was used as a positive control. Scopolamine induced histopathological changes in rats' prefrontal cortex and hippocampus in addition to ß-amyloid plaque deposition. Furthermore, scopolamine treatment promoted oxidative stress and acetylcholinesterase activity. On the other hand, treatment with Salvia extracts corrected the histological changes induced by scopolamine and significantly reduced ß-amyloid deposition. Moreover, both oxidative stress markers and acetylcholinesterase activity were ameliorated by Salvia treatment. Using virtual docking to the active sites of the human acetylcholinesterase crystal structure, salvianolic acid K, rosmarinic acid and salvianolic acid C showed the best fitting binding modes to active sites of acetylcholinesterase. Accordingly, the present study demonstrates the beneficial effects of Salvia species from Egypt and Jordan against scopolamine-induced AD-like disorder.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

Cognitive improvement effect of nervonic acid and essential fatty acids on rats ingesting Acer truncatum Bunge seed oil revealed by lipidomics approach.

Acer truncatum Bunge seed oil (ASO) is rich in ω-9 (53.93%) and ω-6 (30.7%) fatty acids (FAs) and characterized by 3-7% nervonic acid (NA, C24:1ω-9). Evidence suggests that ω-9 FAs such as NA participate in processes of cognitive improvement; however, their mechanism remains ambiguous. In this study, we investigated the effect of ASO on rat memory and the change in lipid profiling and underlying metabolism. After ASO was administrated to rats for one, three and seven days, their capacity for learning and memory significantly increased via the MWM test. Lipid profiling showed alterations in a wide range of metabolic features after ASO was administrated to the rats, in which sphingolipids (SP) in the serum and glycerophospholipids (GP) in the brain were regulated significantly. The changes in the fatty acids in the serum and brain showed the synergetic effects of NA, EA, OA and DHA, where NA, EA and OA exhibited similar change trends. The enrichment analysis based on KEGG indicated that ASO supplementation evoked the pathways of neurotrophin signaling, glycerophospholipid metabolism and sphingolipid metabolism, which are related to memory and cognition improvement. Among the metabolites with different molecular forms, the biomarkers with C24:1ω-9 chains exhibited a positive correlation with others both in the serum SP and brain GP. These results suggest the synergistic effects of ω-9 FAs and that their conversion into each other may result in enhanced cognition in rats ingesting Acer truncatum Bunge seed oil.

Elevated hippocampal mGlut2 receptors in rats with metabolic syndrome-induced-memory impairment, possible protection by vitamin D.

BACKGROUND: Metabolic syndrome patients are commonly prone to major health problems as cardiovascular diseases, diabetes mellitus, chronic kidney disease, cancer and neuropsychological complications including dementia. OBJECTIVES: This research investigates mechanisms linking metabolic syndrome to cognitive impairment and possible impact of vitamin D supplementation. METHODS: Forty male Wistar rats were divided into 4 groups. Control, metabolic syndrome (20% fructose solution in drinking water for 12 weeks, vitamin D supplemented (500 IU/kg/day)) and metabolic syndrome supplemented with vitamin D. Animals were assessed for spatial memory, hippocampal expression of SNAP 25, VAMP and mGlut2 receptor and hippocampus histological examination. Animals with metabolic syndrome showed prolonged acquisition and retention latencies in morris water maze, decreased hippocampal expression of SNAP 25 and VAMP and increased mGlut2 expression. Histologically CA1, CA3 regions and dentate nucleus revealed increase in degenerated neurons and glia cells with decreased pyramidal cell layer thickness. Vitamin D supplementation mitigated alterations induced by metabolic syndrome. CONCLUSIONS: Metabolic syndrome decreased hippocampal synaptic proteins and altered glutamatergic transmission and increased hippocampal neuronal degeneration. Vitamin D supplementation offered neuroprotective effects.

Neuropsychopharmacological profiling of scoparone in mice.

Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5-25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC-ESI-MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans.

Analysis of the therapeutic effect of Dimu Ningshen (TCM formula) on attention deficit hyperactivity disorder based on gut microbiota and serum metabolomics.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder diagnosed during adolescence and adulthood. Assessment of the long-term risks of the current drugs for ADHD treatment has been insufficient, and little is known concerning the long-term therapeutic effects of psychostimulants. Commercially available traditional Chinese medicine compound oral preparations [e.g., Dimu Ningshen (DMNS)] have been widely used in the clinical treatment of ADHD, but their influence on the interaction between gut microbes and potential metabolomes remains inconclusive. METHODS: We used a series of behavioral experiments to evaluate the behavioral effects of DMNS on adolescent and adult ADHD rats and used 16S rDNA sequencing of gut microbes and nontarget metabolomics to evaluate the potential pathogenesis of ADHD and explore the biological mechanism of DMNS in ADHD treatment. RESULTS: For the first time, DMNS was shown to reduce the excessive activity of adult and adolescent ADHD rats and improve the attention deficit of adult ADHD rats. DMNS improved the structural composition of the ADHD gut microbiota and reduced the abundance of Ruminococcaceae_NK4A214_group, Ruminococcus_2, and Eubacterium_nodatum_group. Simultaneously, DMNS increased the circulating levels of peripheral monoamine neurotransmitter precursors (e.g., phenylalanine) and reduced the circulating levels of peripheral fatty acid amides (e.g., oleamide). Finally, the changes in the ADHD serum metabolites were strongly correlated with the gut microbiota. CONCLUSION: DMNS has a good effect in treating ADHD, and it may exert this effect by regulating the gut microbiota and affecting metabolites in the peripheral circulation.

Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. AIM OF THE STUDY: To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. MATERIALS AND METHODS: 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. RESULTS: The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. CONCLUSION: The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms.

Qisheng Wan formula ameliorates cognitive impairment of Alzheimer's disease rat via inflammation inhibition and intestinal microbiota regulation.

ETHNOPHARMACOLOGY RELEVANCE: Qisheng Wan formula (QWF) was first described in the book Sheng Ji Zong Lu in 1117. The book states that QWF can cure forgetfulness, improve the mind, and make people smart. Hence, QWF has been widely used to treat patients with forgetfulness or dementia. QWF, a classic Chinese formulation, comprises seven herbal drugs: the sclerotium of Poria cocos (Schw.) Wolf, bark of Cinnamomum cassia Presl, root of Polygala tenuifolia Willd., root and rhizome of Panax ginseng C. A. Mey., root of Asparagus cochinchinensis (Lour.) Merr., root and rhizome of Acorus tatarinowii Schott, and root bark of Lycium chinense Mill. AIM OF THE STUDY: This study aimed to utilize modern pharmacological methods to evaluate the therapeutic effects and explore the underlying mechanism of QWF action on rats with Alzheimer's disease (AD). MATERIALS AND METHODS: The chemical profile of QWF was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The AD rat model was established via a bilateral intraventricular injection of amyloid-ß (1-42) (Aß1-42). The rats were subsequently treated daily with QWF for 4 weeks. The Morris water maze test was performed to evaluate the cognition processes in the rats, whereas histological changes in the hippocampus were observed using hematoxylin and eosin staining. The expression levels of Aß1-42, nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the hippocampus and colon were assessed. Moreover, the diversity and composition of the intestinal microbiota were analyzed using 16S rDNA gene sequencing. RESULTS: One hundred and fourteen compounds were characterized in QWF. QWF significantly ameliorated the cognition processes and histopathological damages due to AD in rats by decreasing the deposition of Aß1-42 and downregulating the expression of NF-κB, TNF-α, and IL-6. QWF also modulated changes in the diversity and composition of intestinal microbiota to suppress the relative abundance of inflammation-associated microbiota. CONCLUSION: This study showed that QWF can suppress proinflammatory factors and modulate the intestinal microbiota in AD rats.

Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi Regulate the Brain Tau Hyperphosphorylation at Multiple Sites Induced by Composited Aß in Rats.

BACKGROUND: Neurofibrillary Tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's Disease (AD), arethe main pathomechanisms of neuronal degeneration, which indicate a sign of brain disorder. NFTs are positively correlated with the degree of cognitive impairment in AD. OBJECTIVE: The objective of this study isto investigate the effect of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by ß-amyloid protein 25-35 (Aß25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-ß1(RHTGF-ß1) (composited Aß) in rats. METHODS: The AD rat models were established by intracerebroventricular injection of Aß25-35 and AlCl3 combined with RHTGF-ß1. On day 45, after the operation, the Morris water maze test was conducted to screen the memory impairment of AD models. The successful model rats were randomly divided into the model group and the three-dose drug group. The drug group rats were orally administered SSF daily for 38 days. Western blotting was performed to detect the protein expression of P-Tau (Thr 181), P-Tau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-- Tau (Ser 396), and P-Tau (Ser 404) in the hippocampus and cerebral cortex of rats. RESULTS: Compared with the sham group, the expression of P-Tau (Thr 181), P-Tau (Thr 217), P-- Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404)was significantly increased in the hippocampus and cerebral cortex of the model group (P < 0.01). However, the three doses of SSF, i.e., 35, 70, and 140 mg/kg, regulated the expression of phosphorylated Tau proteinto varying degrees in the hippocampus and cerebral cortex of AD model rats (P < 0.01). CONCLUSION: SSF could significantly reduce the protein expression levels of P-Tau (Thr 181), PTau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404), induced by the intracerebroventricular injection of composited Aß, in rats' brain. These results indicated that the neuro-protection and the improvement in the impaired memory of rats by SSF were due to the inhibition of hyperphosphorylation of Tau protein at multiple sites in rats' brain.

Conifer Essential Oils Reversed Amyloid Beta1-42 Action by Modulating BDNF and ARC Expression in The Rat Hippocampus.

BACKGROUND: The conifer species Pinus halepensis (Pinaceae) and Tetraclinis articulata (Cupressaceae) are widely used in traditional medicine due to their beneficial health properties. OBJECTIVE: This study aimed to investigate the mechanisms by which P. halepensis and T. articulata essential oils (1% and 3%) could exhibit neuroprotective effects in an Alzheimer's disease (AD) rat model, induced by intracerebroventricular (i.c.v.) administration of amyloid beta1-42 (Aß1-42). METHODS: The essential oils were administered by inhalation to the AD rat model, once daily, for 21 days. DNA fragmentation was assessed through a Cell Death Detection ELISA kit. Brainderived neurotrophic factor (BDNF), activity-regulated cytoskeleton-associated protein (ARC), and interleukin-1ß (IL-1ß) gene expressions were determined by RT-qPCR analysis, while BDNF and ARC protein expressions were assessed using immunohistochemistry technique. RESULTS: Our data showed that both essential oils substantially attenuated memory impairments, with P. halepensis mainly stimulating ARC expression and T. articulata mostly enhancing BDNF expression. Also, the inhalation of essential oils reduced IL-1ß expression and induced positive effects against DNA fragmentation associated with Aß1-42-induced toxicity, further contributing to the cognitive improvement in the rats with the AD-like model Conclusion: Our findings provide further evidence that these essential oils and their chemical constituents could be natural agents of therapeutic interest against Aß1-42-induced neurotoxicity.

Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine.

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is a neurological disorder of the brain characterized by periodic and unpredictable occurrence of a transient behavior alteration due to the rhythmic, synchronous and disordered firing of brain neuron. Worldwide, approximately 50 million people currently live with epilepsy and close to 80% of people with epilepsy live in poor countries. However, it was noticed in many countries worldwide that people with epilepsy and their families suffer from stigma and discrimination and that situation exposes them to high psychological conditions such as depression and anxiety as well as more physical problems including bruising and fractures from injuries related to seizures. However, several plants-based products used for epilepsy and anxiety treatments in different system of folk medicine have exhibited a significant anti-epileptic and antianxiety activities using animal models with fewer side effects. AIM OF THE STUDY: The study aimed at evaluating the antiepileptic, status post-epilepticus and anxiolytic effects of Cymbopogon giganteus decoction in rat model induced by pilocarpine. MATERIALS AND METHODS: A total of 90 rats were partitioned into 7 groups and treated as follow: animals of groups I (normal control) and II (considered the negative control) received distilled water (10 mL/kg); while groups III, IV, V, and VI were treated with the C. giganteus extract at 34, 85, 170 and 340 mg/kg p.o, respectively; and the group VII (considered positive control) received sodium valproate at 300 mg/kg, i.p. After 40 min post-treatment, a single dose of n-methyl-scopolamine (1 mg/kg, i.p) was administered to animals of groups (II, III, IV, V, VI, VII) followed by pilocarpine (360 mg/kg, i.p). Animal of group I (normal group) received distilled water. Rats were further observed for 6 h to evaluate the severity and the duration of the acute seizures of epilepsy according to Racine scale. Anxious behavior status post-epilepticus was also assessed in the same rats used above in the Elevated Plus Maze and number of entries into the open or closed arms and the time spent on either open or closed arms of the platform were recorded. Animals were also evaluated on Open Field Test and the number of rearing, crossing, grooming, defecation and center time were registered. RESULTS: C. giganteus decoction significantly (P < 0.05) reduced the animal mortality, the number and duration of convulsions and effectively increased the latency of convulsions. The plant extract significantly (P < 0.05) improved GSH level and SOD activity, reduced MDA and CAT activity, increased GABA level and decreased GABA-t activity in hippocampus. The anxiety induced by pilocarpine was also significantly (P < 0.05) inhibited by the extract of the plant. CONCLUSIONS: Thus, C. giganteus has demonstrated its antiepileptic and anxiolytic activities in rat model and may be used as preventive measure for patients suffering from epilepsy seizures and anxiety.

Origanum vulgare ssp. hirtum (Lamiaceae) Essential Oil Prevents Behavioral and Oxidative Stress Changes in the Scopolamine Zebrafish Model.

Origanum vulgare ssp. hirtum has been used as medicinal herbs promoting antioxidant, anti-inflammatory, antimicrobial, and neuroprotective activities. We investigated the protective effects and the mechanism of O. vulgare ssp. hirtum essential oil (OEO) on cognitive impairment and brain oxidative stress in a scopolamine (Sco)-induced zebrafish (Danio rerio) model of cognitive impairment. Our results show that exposure to Sco (100 µM) leads to anxiety, spatial memory, and response to novelty dysfunctions, whereas the administration of OEO (25, 150, and 300 µL/L, once daily for 13 days) reduced anxiety-like behavior and improved cognitive ability, which was confirmed by behavioral tests, such as the novel tank-diving test (NTT), Y-maze test, and novel object recognition test (NOR) in zebrafish. Additionally, Sco-induced brain oxidative stress and increasing of acetylcholinesterase (AChE) activity were attenuated by the administration of OEO. The gas chromatography-mass spectrometry (GC-MS) analyses were used to elucidate the OEO composition, comprising thymol (38.82%), p-cymene (20.28%), and γ-terpinene (19.58%) as the main identified components. These findings suggest the ability of OEO to revert the Sco-induced cognitive deficits by restoring the cholinergic system activity and brain antioxidant status. Thus, OEO could be used as perspective sources of bioactive compounds, displaying valuable biological activities, with potential pharmaceutical applications.

Ganoderic acid improves 5-fluorouracil-induced cognitive dysfunction in mice.

5-Fluorouracil (5-FU) is a chemotherapeutic drug with a good anti-cancer effect on various types of cancers, such as colorectal cancer and breast cancer. However, previous studies have found that 5-FU could induce cognitive deficit in clinics. As ganoderic acid, isolated from Ganoderma lucidum, has a protective effect on neurons, this study investigated the effects of ganoderic acid (GA) against 5-FU-induced cognitive dysfunction with a series of behavioral tests and related indicators. Experimental results showed that GA significantly prevented the reduction of spatial and non-spatial memory in 5-FU-treated mice. In addition, GA not only ameliorated the damage to hippocampal neurons and mitochondrial structure, but also significantly improved abnormal protein expression of mitochondrial biogenesis related marker PGC-1α, and mitochondrial dynamics related markers MFN2, DRP1 and FIS1 in the hippocampi of 5-FU-treated mice. Moreover, GA could up-regulate the expression of neuronal survival and growth-related proteins, such as BDNF, p-ERK, p-CREB, p-Akt, p-GSK3ß, Nrf2, p-mTOR, and p-S6, in the hippocampi of 5-FU-treated mice. These results suggest that GA could prevent cognitive dysfunction in mice treated with 5-FU via preventing mitochondrial impairment and enhancing neuronal survival and growth, which provide evidence for GA as a promising adjunctive therapy for chemotherapy related cognitive impairment in clinics.

Adaptogenic activity of Cinnamomum camphora, Eucalyptus globulus, Lavandula stœchas and Rosmarinus officinalis essential oil used in North-African folk medicine.

Depressive anxiety is one of the most emotional disorders in our industrial societies. Many treatments of phobias exist and are based on plant extracts therapies, which play an important role in the amelioration of the behavior. Our study aimed to evaluate the adaptogenic activity of different essential oils provided from local plants: Cinnamomum camphora (Camphora), Eucalyptus globulus (Blue gum), Lavandula stœchas (Topped lavender) and Rosmarinus officinalis (Rosemary) on Wistar rats. The adaptogenic activity was evaluated on the elevated plus-maze. The efficacy of the extract (200 mL/kg) was compared with the standard anxiolytic drug Diazepam® 1 mg. Animals administered by the essential oil of Lavandula stœchas, Cinnamomum camphora, Rosmarinus officinalis and Eucalyptus globulus showed a behavior similar to those treated with Diazepam®. For groups treated with the following essential oils: Rosmarinus officinalis, Lavandula stoechas and Cinnamomum camphora at a dose of 200 mL/kg, we notice an increase in the time spent on the open arms of the elevated plus-maze and a decrease in time spent on the closed arms of the elevated plus-maze, especially for Rosmarinus officinalis, which explains the anxiolytic effect of these plants. We also notice a decrease in the number of entries in closed arms, open arms and the number of passing to the central square. The increase in the number of entries to open arms with Eucalyptus globulus essential oil shows a reduction in anxiety behavior in rodents and this shows that these plants have an inhibitory effect.