Effect of alkaloid extracted from Huperzia phlegmaria on cognitive deficits scopolamine-induced in mice

2020 ◽  
Vol 16 ◽  
Author(s):  
Dang Kim Thu ◽  
Dao Thi Vui ◽  
Nguyen Thi Ngoc Huyen ◽  
Nguyen Thi Thanh Binh ◽  
Nguyen Thi Huyen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Brain ◽  
Cognitive Deficits ◽  
Inhibitory Activity ◽  
Water Maze ◽  
Ache Activity ◽  
Y Maze ◽  
Ache Inhibitory Activity ◽  
Kinetic Inhibition ◽  
Brain Tissues

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had the strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpPAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 µg/mL. Scopolamine induced the cognitive impairment in Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both dose (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.

Pharmacological Inhibition of Transient Receptor Potential Melastatin 2 (TRPM2) Channels Attenuates Diabetes-induced Cognitive Deficits in Rats: A Mechanistic Study

2020 ◽  
Vol 17 (3) ◽  
pp. 249-258 ◽  
Author(s):  
Pavan Thapak ◽  
Mahendra Bishnoi ◽  
Shyam S. Sharma
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Ache Activity ◽  
Transient Receptor Potential ◽  
Mrna Level ◽  
Receptor Potential ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channels ◽  
Transient Receptor ◽  
Gsk 3Β

Background: Diabetes is a chronic metabolic disorder affecting the central nervous system. A growing body of evidence has depicted that high glucose level leads to the activation of the transient receptor potential melastatin 2 (TRPM2) channels. However, there are no studies targeting TRPM2 channels in diabetes-induced cognitive decline using a pharmacological approach. Objective: The present study intended to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB), a TRPM2 inhibitor, in diabetes-induced cognitive impairment. Methods: Streptozotocin (STZ, 50 mg/kg, i.p.) was used to induce diabetes in rats. Animals were randomly divided into the treatment group, model group and age-matched control and pre se group. 2-APB treatment was given for three weeks to the animals. After 10 days of behavioural treatment, parameters were performed. Animals were sacrificed at 10th week of diabetic induction and the hippocampus and cortex were isolated. After that, protein and mRNA expression study was performed in the hippocampus. Acetylcholinesterase (AchE) activity was done in the cortex. Results: : Our study showed the 10th week diabetic animals developed cognitive impairment, which was evident from the behavioural parameters. Diabetic animals depicted an increase in the TRPM2 mRNA and protein expression in the hippocampus as well as increased AchE activity in the cortex. However, memory associated proteins were down-regulated, namely Ca2+/calmodulin-dependent protein kinase II (CaMKII-Thr286), glycogen synthase kinase 3 beta (GSK-3β-Ser9), cAMP response element-binding protein (CREB-Ser133), and postsynaptic density protein 95 (PSD-95). Gene expression of parvalbumin, calsequestrin and brain-derived neurotrophic factor (BDNF) were down-regulated while mRNA level of calcineurin A/ protein phosphatase 3 catalytic subunit alpha (PPP3CA) was upregulated in the hippocampus of diabetic animals. A three-week treatment with 2-APB significantly ameliorated the alteration in behavioural cognitive parameters in diabetic rats. Moreover, 2-APB also down-regulated the expression of TRPM2 mRNA and protein in the hippocampus as well as AchE activity in the cortex of diabetic animals as compared to diabetic animals. Moreover, the 2-APB treatment also upregulated the CaMKII (Thr-286), GSK-3β (Ser9), CREB (Ser133), and PSD-95 expression and mRNA levels of parvalbumin, calsequestrin, and BDNF while mRNA level of calcineurin A was down-regulated in the hippocampus of diabetic animals. Conclusion: : This study confirms the ameliorative effect of TRPM2 channel inhibitor in the diabetes- induced cognitive deficits. Inhibition of TRPM2 channels reduced the calcium associated downstream signaling and showed a neuroprotective effect of TRPM2 channels in diabetesinduced cognitive impairment.

scholarly journals Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhong-he Liu ◽  
Hong-guang Chen ◽  
Pan-feng Wu ◽  
Qing Yao ◽  
Hong-ke Cheng ◽  
...  
Keyword(s):  
Body Weight ◽  
Cerebral Cortex ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Ache Activity ◽  
Memory Deficits ◽  
Test Body ◽  
Morris Water Maze Test ◽  
Diabetic Mice ◽  
Mice Model

Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice.Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured.Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE.Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

scholarly journals The ApoE-dependent Neuroprotective Effects of Sesamol on Diet-induced Obese Mice: The Role of Gut Microbiota and SCFAs (P06-049-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tian Yuan ◽  
Zhigang Liu ◽  
Xuebo Liu
Keyword(s):  
Fatty Acids ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Short Chain Fatty Acids ◽  
Microbial Metabolites ◽  
Neuroprotective Effects ◽  
Y Maze ◽  
Plus Maze ◽  
Synapse Ultrastructure

Abstract Objectives Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain. Methods Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively. Results Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate. Conclusions To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China. Supporting Tables, Images and/or Graphs

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

2012 ◽  
Vol 30 (4) ◽  
pp. 339-345 ◽  
Author(s):  
Guomin Li ◽  
Xuezhu Zhang ◽  
Haiyan Cheng ◽  
Xuemei Shang ◽  
Hui Xie ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Neuron Loss ◽  
Neuron Density ◽  
Maze Test ◽  
Samp8 Mice

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.

scholarly journals Dimethyl fumarate prevents acute lung injury related cognitive impairment potentially via reducing inflammation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaowei Wang ◽  
Yanbo Wang ◽  
Haiyan Pan ◽  
Ci Yan
Keyword(s):  
Cognitive Impairment ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Maze ◽  
Dimethyl Fumarate ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Maze Test ◽  
Evans Blue Extravasation ◽  
Brain Tissues

Abstract Objective Dimethyl fumarate (DMF) has been reported to exert a protective role against diverse lung diseases and cognitive impairment-related diseases. Thus this study aimed to investigate its role on acute lung injury (ALI) and related cognitive impairment in animal model. Methods C57BL/6 mice were divided into four groups: control group, DMF group, ALI group, and ALI + DMF group. For ALI group, the ALI mice model was created by airway injection of LPS (50 μL, 1 μg/μL); for ALI + DMF group, DMF (dissolved in 0.08% methylcellulose) was treated twice a day for 2 days, and on the third day, mice were injected with LPS for ALI modeling. Mice pre-administered with methylcellulose or DMF without LPS injection (PBS instead) were used as the control group and DMF group, respectively. Morris water maze test was performed before any treatment (0 h) and 6 h after LPS-induction (54 h) to evaluate the cognitive impairment of mice. Next, the brain edema and blood brain barrier (BBB) permeability of ALI mice were assessed by brain water content, Evans blue extravasation and FITC-Dextran uptake assays. In addition, the effect of DMF on the numbers of total cells and neutrophils, protein content in BALF were quantified; the inflammatory factors in BALF, serum, and brain tissues were examined by ELISA, qRT-PCR, and Western blot assays. The effect of DMF on the cognitive impairment-related factor HIF-1α level in lung and brain tissues was also examined by Western blot. Results DMF reduced the numbers of total cells, neutrophils and protein content in BALF of ALI mice, inhibited the levels of IL-6, TNF-α and IL-1β in BALF, serum and brain tissues of ALI mice. The protein expressions of p-NF-κB/NF-κB and p-IKBα/IKBα was also suppressed by DMF in ALI mice. Morris water maze test showed that DMF alleviated the cognitive impairment in ALI mice by reducing the escape latency and path length. Moreover, DMF lessened the BBB permeability by decreasing cerebral water content, Evans blue extravasation and FITC-Dextran uptake in ALI mice. The HIF-1α levels in lung and brain tissues of ALI mice were also lessened by DMF. Conclusion In conclusion, DME had the ability to alleviate the lung injury and cerebral cognitive impairment in ALI model mice. This protective effect partly associated with the suppression of inflammation by DMF.

scholarly journals Subarachnoid hemorrhage leads to early and persistent functional connectivity and behavioral changes in mice

2019 ◽  
Author(s):  
David Y Chung ◽  
Fumiaki Oka ◽  
Gina Jin ◽  
Andrea Harriott ◽  
Sreekanth Kura ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Connectivity ◽  
Open Field ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Time Points ◽  
Rotarod Performance ◽  
Optical Intrinsic Signal ◽  
Y Maze

AbstractAneurysmal subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits. Studies in survivors of SAH show an association between persistent cognitive deficits and alterations in resting state functional connectivity (RSFC). However, modalities commonly used to assess RSFC in humans, such as fMRI, have practical limitations in small animals. Therefore, we used non-invasive functional optical intrinsic signal imaging to determine the effect of SAH on measures of RSFC in mice at early (day 4), intermediate (1 month), and late (3 months) time points after prechiasmatic arterial blood injection. We assessed Morris water maze, open field test, Y-maze, and rotarod performance from approximately 2 weeks to 3 months after SAH induction. We found qualitative and quantitative differences in seed-based connectivity maps between sham and SAH mice. SAH reduced motor, retrosplenial and visual seed-based connectivity indices, which persisted in retrosplenial and visual cortex seeds at 3 months. Seed-to-seed connectivity analysis confirmed attenuation of correlation coefficients in SAH mice, which persisted in predominantly posterior network connections at later time points. Seed-independent global and interhemispheric indices of connectivity revealed decreased correlations following SAH for at least 1 month. SAH led to Morris water maze hidden platform and open field deficits at 2 weeks, and Y-maze deficits for at least 3 months, without altering rotarod performance. In conclusion, experimental SAH leads to early and persistent alterations both in hemodynamically-derived measures of RSFC and in cognitive performance.

scholarly journals Trigeminal Neuralgia Induced by Cobra Venom Leads to Cognitive Deficits Associated with Downregulation of CREB/BDNF Pathway

2017 ◽  
Vol 2 (20;2) ◽  
pp. 53-67
Author(s):  
Jianxiong An
Keyword(s):  
Cognitive Impairment ◽  
Trigeminal Neuralgia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Memory Deficits ◽  
Cobra Venom ◽  
Spatial Learning And Memory ◽  
Bdnf Pathway

Background: Chronic pain often results in cognitive impairment. Our previous study showed that trigeminal neuralgia induced by cobra venom leads to spatial learning and memory deficits, although the underlying mechanism remains unclear. However, recent evidence indicates that the c-AMP-responsive element binding protein (CREB)/brain derived neurotrophic factor (BDNF) pathway plays a critical role in various etiologies of cognitive deficits. Objectives: Our aim was to explore the CREB/BDNF pathway to determine the molecular mechanisms involved in the pathogenesis of cognitive impairment caused by cobra venominduced trigeminal neuralgia. Study Design: A randomized, controlled animal study. Setting: Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University. Methods: Fifty male Sprague–Dawley rats were randomly divided into 3 groups: cobra venom group, sham group, and control group. Cobra venom or saline was injected into the sheath of the infraorbital nerve (ION), respectively. Video recordings and mechanical thresholds were used to analyze changes in behavioral activity 3 days before surgery and 4, 7, 14, 21, 28, and 56 days after surgery. Morris water maze tests were conducted at 4- and 8-week time points after surgery to evaluate spatial learning and memory. We also investigated expression changes of phosphorylated CREB (p-CREB) and BDNF in the hippocampus and prefrontal cortex (PFC) using western blotting and immunohistochemistry. Results: Cobra venom-treated rats exhibited significant changes in face grooming, as well as exploratory and resting behaviors, compared with the control group and sham group (both P < 0.001). Rats in the cobra venom group exhibited slightly impaired acquisition (P < 0.05) without memory deficits (P > 0.05) in the first water maze protocol. In the second water maze test, rats in the cobra venom group exhibited spatial learning and memory deficits, with fewer platform site crossings during the probe trial (P < 0.05). Moreover, results showed decreased p-CREB and BDNF expressions in the hippocampus and PFC in the cobra venom group, with significant differences at 9 weeks post-surgery (P < 0.05). Limitations: No signaling inhibitor or genetic manipulation was administered to further confirm upstream factors of the CREB/BDNF pathway in cognitive deficits caused by chronic trigeminal neuralgia. Conclusions: The findings suggest that cognitive impairment caused by cobra venom-induced trigeminal neuralgia is associated with downregulation of the CREB/BDNF pathway in the hippocampus and PFC. Key words: Cognitive impairment, the CREB/BDNF pathway, cobra venom, trigeminal neuralgia, hippocampus, prefrontal cortex, free behavior, Morris water maze

scholarly journals Acetylcholinesterase Inhibitory Activity of Alkaloids Isolated from Stephania venosa

2016 ◽  
Vol 11 (12) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Sumet Kongkiatpaiboon ◽  
Nongnaphat Duangdee ◽  
Saisuree Prateeptongkum ◽  
Wanna Chaijaroenkul
Keyword(s):  
Inhibitory Activity ◽  
Ache Activity ◽  
Hplc Analysis ◽  
Inhibitory Effect ◽  
Inhibition Assay ◽  
Phytochemical Screening ◽  
Ache Inhibition ◽  
Ache Inhibitory Activity ◽  
Inhibitory Potential ◽  
Protoberberine Alkaloid

Stephania venosa (Blume) Spreng or “Sa-Bu-Leud” is a Thai medicinal plant used for treatment of cancer and diabetes, and as a blood-tonic and aphrodisiac. This plant contains alkaloids as its major components and has been of interest for its acetylcholinesterase (AChE) inhibitory activity. Phytochemical screening of S. venosa was made using HPLC analysis and showed the chemical variation between the same species from different provenances. Fractionation of S. venosa extract yielded three alkaloids, namely, dicentrine, crebanine, and tetrahydropalmatine. AChE inhibitory potential of the isolated alkaloids was evaluated using Ellman's AChE inhibition assay. Dicentrine, crebanine, and tetrahydropalmatine inhibited AChE activity with IC50 values of 93.5, 86.6, and 168.6 μg/mL, respectively. The AChE inhibitory activity of the tertiary protoberberine alkaloid, tetrahydropalmatine, was lower than that of the aporphine alkaloids, dicentrine and crebanine, whereas the quaternary protoberberine alkaloid, berberine, showed a higher AChE inhibitory effect than the others.

scholarly journals Post-stroke cognitive impairment on the Mini-Mental State Examination primarily relates to left middle cerebral artery infarcts

2021 ◽  
pp. 174749302098455
Author(s):  
Nick A Weaver ◽  
Angelina K Kancheva ◽  
Jae-Sung Lim ◽  
J Matthijs Biesbroek ◽  
Irene MC Huenges Wajer ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cognitive Deficits ◽  
Mini Mental State Examination ◽  
Left Middle Cerebral Artery ◽  
Post Stroke ◽  
Lesion Symptom Mapping ◽  
State Examination ◽  
Left Middle

Background Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods We examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67 ± 12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment. Results Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p < 0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.

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