Objective To investigate the protective effect of resveratrol (RSV) on improving cognitive function in severely burned rats and its possible mechanism. Methods 18 male SD rats aged 18-20 months were randomly divided into 3 groups: control group, model group and RSV group, with 6 rats in each group. After successful modeling, the rats in RSV group were gavaged once daily with RSV (20 mg/kg). Meanwhile, the rats in control group and model group were gavaged once daily with an equal volume of sodium chloride solution. After 4 weeks, the cognitive function of all rats was estimated by Step-down Test. The concentration of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) protein in serum of rats were detected by ELISA. The expression of IL-6, TNF-α mRNA and protein were estimated by real-time PCR and Western blotting. The apoptosis of hippocampal neurons was tested by terminal deoxynuclectidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The expression of nuclear transcription factor-κB (NF-κB)/c-Jun N-terminal kinase (JNK) pathway-related proteins in hippocampus were assessed by Western blotting. Results Compared with the rats in model group, rats in RSV group exhibited improved cognitive function. Consistently, the rats in RSV group had a reduced concentration of TNF-α and IL-6 in serum, decreased mRNA and protein expressions of TNF-α and IL-6 in hippocampus, and decreased apoptosis rate and relative expression of p-NF-κB p65/NF-κB p65 and p-JNK/JNK in hippocampal neurons. Conclusion RSV alleviates inflammatory response and hippocampal neuronal apoptosis by inhibiting NF-κB/JNK pathway, thereby improving cognitive function in severely burned rats.
Resveratrol/pharmacology* ; Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Burns/drug therapy* ; Cognition/drug effects* ; Hippocampus/metabolism* ; MAP Kinase Signaling System ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-6/blood* ; Neurons/drug effects* ; Apoptosis

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.
Aluminum Chloride/adverse effects* ; Alzheimer Disease/drug therapy* ; Animals ; Galactose/metabolism* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Hippocampus/metabolism* ; Mice ; Mice, Inbred BALB C ; Plant Extracts ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; tau Proteins

Animals ; Apoptosis ; Cognition ; Diabetes Mellitus, Experimental/drug therapy* ; Drugs, Chinese Herbal/pharmacology* ; Hippocampus/cytology* ; Moringa/chemistry* ; Neurons/drug effects* ; Plant Leaves/chemistry* ; Rats ; Rats, Sprague-Dawley

PURPOSE: To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury. METHODS: Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups. RESULTS: The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05). CONCLUSION Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.
Animals ; Dexmedetomidine ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Hippocampus ; metabolism ; Immunohistochemistry ; Inflammasomes ; metabolism ; Inflammation Mediators ; metabolism ; Injections, Intraperitoneal ; Interleukin-1beta ; metabolism ; Laparotomy ; adverse effects ; Male ; Microglia ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Rats, Sprague-Dawley ; Time Factors

The purpose of this study was to explore the effects of calcitonin gene-related peptide (CGRP) on the long-term depression (LTD) of hippocampus in mice. Sixty C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP (50, 100, and 200 nmol/L) groups, CGRP + CGRP group and CGRP + APV group (10 mice for each group). The effects of exogenous application of different concentrations of CGRP on synaptic plasticity and LTD in hippocampus of mice were detected by in vitro recording of local field potential. The results showed that higher doses (100 and 200 nmol/L) of CGRP significantly enhanced the induction of LTD in the hippocampus. Moreover, CGRP increased the magnitude of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents. The above-mentioned effects of CGRP were blocked by either CGRP selective antagonist CGRP or NMDA receptor antagonist APV. These results suggest that CGRP can dose-dependently enhance the induction of LTD in hippocampus of mice, and the underlying mechanism involves the mediation of NMDA receptor function.
Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Hippocampus ; drug effects ; Long-Term Synaptic Depression ; drug effects ; Mice ; Mice, Inbred C57BL ; Random Allocation

The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.
Acorus ; chemistry ; Animals ; CA1 Region, Hippocampal ; drug effects ; pathology ; Curcuma ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Epilepsy ; drug therapy ; Hippocampus ; Plant Roots ; chemistry ; Rats ; Rhizome ; chemistry

OBJECTIVE: To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral development of male offspring. METHODS: Pregnant mice were randomly divided into four groups: control- (normal saline), low- [10 mg/(kg•day)], middle- [50 mg/(kg•day)], and high-dose [200 mg/(kg•day)] groups, which received SMM by gavage daily during gestational days 1-18. We measured the levels of short-chain fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mRNA and protein levels of genes involved in the mammalian target of rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western blotting. RESULTS: Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase (SPR), a potential target of mTOR, was inhibited. CONCLUSION In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.
Alcohol Oxidoreductases ; metabolism ; Animals ; Anti-Infective Agents ; toxicity ; Fatty Acids, Volatile ; analysis ; Feces ; chemistry ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Memory ; drug effects ; Mice, Inbred ICR ; Pregnancy ; Prenatal Exposure Delayed Effects ; Sulfamonomethoxine ; toxicity ; TOR Serine-Threonine Kinases ; metabolism

To investigate the effect of triptolide on cognitive dysfunction in vascular dementia rats and its effect on SIRT1/NF-κB pathway,fifty healthy male Sprague-Dawley rats were randomly divided into 5 groups: Sham operation group( Sham group),vascular dementia model group( 2 VO group),triptolide intraperitoneal injection group( TR group),triptolide intraperitoneal injection + EX527 intracerebroventricular administration group( T+E group),EX527 intracerebroventricular administration group( EX527 group). After 4 weeks of modeling,Morris water maze test and object recognition test were used to evaluate the learning and memory ability of rats. The morphological changes of hippocampus in each group were observed in brain tissue. The chemical colorimetry was used to detect the activities of SOD and MDA in hippocampus. IL-6 and TNF-α levels were detected by ELISA. Western blot was used to detect the expression of SIRT1,NF-κB,IκBα and caspase 3 in hippocampus. The results showed that compared with the Sham group,the learning and memory ability of the vascular dementia model rats was reduced,the SOD activity in the hippocampus was decreased,the MDA activity and IL-6 level were increased,the neuronal degeneration changed significantly,the expression of SIRT1 and IκBα was decreased and the expression of caspase 3 and NF-κB was significantly increased. After intervention by triptolide,the level of oxidative stress and the degenerative changes in hippocampus were significantly slowed down. The expression of SIRT1 and IκBα protein was increased and the expression of caspase 3 and NF-κB was significantly decreased. While,after intervention by triptolide and EX527,the expression of SIRT1 was decreased,the levels of oxidative stress and neuronal degeneration in the hippocampus were aggravated,and the learning and memory ability was reduced. The results showed that triptolide could improve cognitive impairment in vascular dementia rats and its mechanism may be related to SIRT1/NF-κB signaling pathway.
Animals ; Cognitive Dysfunction ; drug therapy ; Dementia, Vascular ; drug therapy ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Hippocampus ; drug effects ; Male ; NF-kappa B ; metabolism ; Oxidative Stress ; Phenanthrenes ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Sirtuin 1 ; metabolism

OBJECTIVE: To investigate the effects of Acorus tatarinowii Schott and its active component 5- hydroxymethyl furfural (HMF) on learning and memory and ERK/CREB signal in hippocampus of rats with exercise-induced fatigue. METHODS: SD rats were randomly divided into normal group (A), exercise group (B), exercise + HMF low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H), with ten rats in each group. The rats in group C, D and E were treated with HMF at the doses of 0.10, 1.00 and 3.00 mg. kg by ig. The rats in group F, G and H were treated with the extracts of Acorus tatarinowii Schott at the doses of 0.12, 1.20 and 4.80 g. kg by ig. Learning and memory of rats were tested by the method of water maze experiment, and the expression levels of p-ERK1/2 and p-CREB protein in hippocampus of rats were tested by the method of Western blot in the end of the experiment. RESULTS: The escape latencies of E and H groups were lower than those of groups B, C, D, F and G; and the numbers of plateau crossing were more than those of groups B, C, D, F and G and the expression levels of p-ERK1/2, p-CREB protein were higher than those of groups B, C, D, F and G , respectively(P ＜ 0.01). There was no significant difference in the above indexes among groups A, E and H(P＞0.05) except that the expression levels of p-ERK2 protein in group E were lower than those in group A and H (P＜0.05). CONCLUSION Acorus tatarinowii and its active component- HMF can improve the learning and memory of rats with exercise-induced fatigue, and the mechanism is related to the up-regulation of ERK / CREB signal in hippocampus of rats with exercise-induced fatigue.
Acorus ; chemistry ; Animals ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Fatigue ; drug therapy ; Furaldehyde ; analogs & derivatives ; pharmacology ; Hippocampus ; metabolism ; MAP Kinase Signaling System ; Maze Learning ; drug effects ; Memory ; drug effects ; Physical Conditioning, Animal ; Phytochemicals ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01). CONCLUSION Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.
Animals ; Berberine ; pharmacology ; Cognitive Dysfunction ; drug therapy ; Hippocampus ; Inflammation ; Maze Learning ; drug effects ; Memory ; drug effects ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar