ABSTRACT
Sodium salicylate, one of the non-steroidal anti-inflammatory drugs, is widely prescribed in the clinic, but a high dose of usage can cause hyperactivity in the central nervous system, including the hippocampus. At present, the neural mechanism underlying the induced hyperactivity is not fully understood, in particular, in the hippocampus under an in vivo condition. In this study, we found that systemic administration of sodium salicylate increased the field excitatory postsynaptic potential slope and the population spike amplitude in a dose-dependent manner in the hippocampal dentate gyrus area of rats with in vivo field potential extracellular recordings, which indicates that sodium salicylate enhances basal synaptic transmission and neural excitation. In the presence of picrotoxin, a GABA-A receptor antagonist, sodium salicylate failed to increase the initial slope of the field excitatory postsynaptic potential and the amplitude of the population spike in vivo. To further explore how sodium salicylate enhances the neural excitation, we made whole-cell patch-clamp recordings from hippocampal slices. We found that perfusion of the slice with sodium salicylate decreased electrically evoked GABA receptor-mediated currents, increased paired-pulse ratio, and lowered frequency and amplitude of miniature inhibitory postsynaptic currents. Together, these results demonstrate that sodium salicylate enhances the neural excitation through suppressing GABAergic synaptic transmission in presynaptic and postsynaptic mechanisms in the hippocampal dentate gyrus area. Our findings may help understand the side effects caused by sodium salicylate in the central nervous system.
Subject(s)
Hippocampus , Sodium Salicylate , Animals , Dentate Gyrus/physiology , Excitatory Postsynaptic Potentials/physiology , Hippocampus/physiology , Rats , Sodium Salicylate/pharmacology , Synaptic Transmission/physiologyABSTRACT
OBJECTIVE: The objective of this study was to evaluate the relationship of periodontal disease with depression and anxiety via a systematic review and meta-analysis. METHOD: We systematically searched the EMBASE, PubMed, Web of Science, PsycINFO, and SinoMed databases (until August 4, 2019) with language restricted to English and Chinese. Case-control, cross-sectional, and cohort studies that calculated the risk ratio (RR), odds ratio (OR)/prevalence OR (POR), and hazard ratio (HR) of depression/anxiety with periodontal disease or the OR/POR/RR/HR of periodontal disease caused by depression/anxiety were included. Observational studies that reported the depression/anxiety scale score of patients with periodontal disease and healthy periodontal subjects aged ≥14 years were also included. We used the standard format to extract the following information from each included study: author/s, survey year, study design, age of participants, periodontal disease definition, depression/anxiety measurement, and summary of results. The Newcastle-Ottawa scale was used to ascertain the quality of the included citations. RESULTS: After screening, 40 studies were included. A meta-analysis of the case-control studies showed that periodontal disease was positively associated with depression (OR = 1.70, 95% confidence interval [CI] â= 1.01-2.83). A meta-analysis of 12 studies showed that periodontal disease was significantly correlated with anxiety (OR = 1.36, 95% CI = 1.11-1.66). A meta-analysis of 18 studies showed that subjects with periodontal disease had higher depression scale score (standardized mean difference [SMD] = 1.05, 95% CI = 0.68-1.41) and anxiety scale score (SMD = 0.70, 95% CI = 0.44-0.96). CONCLUSION: Periodontal disease is associated with emotional disorders. However, the high degree of heterogeneity among studies should be considered. More high-quality prospective studies are required to confirm the relationship.
Subject(s)
Depression , Periodontal Diseases , Aged , Anxiety/complications , Anxiety/epidemiology , Cross-Sectional Studies , Depression/complications , Depression/epidemiology , Humans , Periodontal Diseases/complications , Periodontal Diseases/epidemiology , Prospective StudiesABSTRACT
In this work, a green enzyme-linked immunosorbent assay (ELISA) based on the single-stranded binding protein (SSB)-assisted aptamer was designed for biosensing applications. Combined with the biotin-streptavidin (SA) system and the high catalytic activity of horseradish peroxidase (HRP), this SSB-assisted aptamer sensor was applied for the detection of aflatoxin B1, ochratoxin A, and zearalenone. In this novel ELISA, mycotoxin-protein conjugations were replaced by SSB to avoid the hazard of mycotoxin, whereas antibodies were replaced by aptamer to avoid the complex and tedious preparation of antibodies. In the absence of target mycotoxins, SSB can bind the aptamer-biotin specifically. Detection was performed using the strong combination of biotin and SA after adding SA-HRP and substrate/chromogen solution, thereby resulting in a strong yellow color signal. In the presence of target mycotoxins, the aptamer-biotin cannot bind to the SSB, thereby leading to a weak yellow color signal. Under optimal conditions, the designed method was successfully applied for the determination of real sample and exhibited high specificity and low limits of detection in corn (112 ng L-1 for aflatoxin B1, 319 ng L-1 for ochratoxin A, and 377 ng L-1 for zearalenone). The green ELISA may also be extended to the detection of other biohazardous targets by changing the aptamer.
Subject(s)
Aptamers, Nucleotide/chemistry , Biotin/chemistry , Enzyme-Linked Immunosorbent Assay , Horseradish Peroxidase/chemistry , Mycotoxins/analysis , Streptavidin/chemistry , Biotin/metabolism , Horseradish Peroxidase/metabolism , Humans , Streptavidin/metabolismABSTRACT
The C-3-OH, C-4 carbonyl oxygen and hydrogenation of C2=C3 bond on the C-ring of 2R,3R-dihydromyricetin (DMY) proved to be not necessary for the antibacterial activity against Staphylococcus aureus. DMY significantly decreased the intracellular ATP of S. aureus cells but had few effects on pHin, proline oxidation, succinate dehydrogenase activity or malate dehydrogenase activity.
Subject(s)
Anti-Bacterial Agents/chemistry , Flavonols/chemistry , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Flavonols/pharmacology , Malate Dehydrogenase/metabolism , Oxidation-Reduction , Proline/chemistry , Succinate Dehydrogenase/metabolismABSTRACT
PURPOSE: Insomnia has become one of the foremost health concerns among workers. Despite a significant number of epidemiological studies have reported on the correlation between insomnia and job stress, comprehensive evidence remains insufficient. Therefore, this research seeks to provide evidence with greater reliability, through summarizing relevant contemporary literature via a meta-analysis. METHODS: Literature from across Europe and Asia that was of both a prospective and cross-sectional design was included, if well-controlled odds ratios were available. The meta-analysis was undertaken in accordance with the guidelines devised by PRISMA, including tests for publication bias and heterogeneity. RESULTS: High job stress was associated with a greater risk of suffering from insomnia (random OR = 1.73, 95% CI 1.46-2.05), and the correlation between effort-reward imbalance and insomnia was statistically significant (random OR = 2.63, 95% CI 1.22-5.69). Higher demand was correlated to a relatively greater risk of insomnia (random OR = 1.35, 95% CI 1.20-1.51), while the pooled effect of low control was not found to be statistically significant. The summary random odds ratio of heavy workload was 2.76, and a pooled odds ratio of 1.67 (fixed, 95% CI 1.11-2.52) was calculated in low social support. With regard to the overall population, work-family conflict was correlated with insomnia (random OR = 2.32, 95% CI 1.53-3.51). The subgroup analysis provided comparable outcomes, for both males (fixed OR = 1.97, 95% CI 1.50-2.57) and females (random OR = 2.80, 95% CI 1.30-6.05). Egger's regression indicated that publication bias may be apparent in the syntheses of effort-reward imbalance, low social support, and work-family conflict (p < 0.05). Heterogeneity was caused by design, measuring the exposure or outcome, in addition to the region where the research was conducted. CONCLUSIONS: The correlation between insomnia and higher levels of job stress, effort-reward imbalance, high demand, heavy workload, and low social support was determined. Publication bias and heterogeneity were partially observed. Furthermore, future studies with improved methodologies and a focus on mechanisms are anticipated.
Subject(s)
Occupational Stress/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Stress, Psychological/epidemiology , Workload/statistics & numerical data , Adult , Asia , Comorbidity , Cross-Sectional Studies , Europe , Female , Humans , Job Satisfaction , Male , Middle Aged , Occupational Stress/psychology , Prospective Studies , Sleep Initiation and Maintenance Disorders/psychology , Social Support , Stress, Psychological/psychology , Workload/psychology , Young AdultABSTRACT
The adherence and biofilm formation of Staphylococcus aureus on food contact surfaces are a major concern for the food industry. Development of antibiofilm agents from polyphenols has drawn much attention due to their potent activity. The present study explored the antibacterial and antibiofilm activities of 2R,3R-dihydromyricetin (DMY) against S. aureus ATCC 29213. It was found that DMY exerted excellent antibacterial and bactericidal properties against S. aureus with minimum inhibitory concentration and minimum bactericidal concentration values of 0.125 and 0.25 mg/mL, respectively. Crystal violet staining and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt reduction assay demonstrated that DMY significantly reduced the biofilm biomass of S. aureus and decreased the metabolic activity of biofilm cells. Micrographs of light microscope and scanning electron microscope confirmed that DMY inhibited the biofilm formation and caused a disintegration of the complex biofilm architecture. Moreover, DMY was highly efficient in reducing the number of sessile S. aureus cells adhered to stainless steel. These results suggested that DMY could have potential application to control S. aureus contamination in a food processing environment.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Flavonols/pharmacology , Staphylococcus aureus/drug effects , Food Contamination/prevention & control , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Stainless SteelABSTRACT
Urena lobata has been used as a traditional medicinal plant in India and China. In this study, we investigated the antimicrobial activity and isolated the active compound from the leaves of U. lobata. The 80% ethanol extract from U. lobata leaves showed an effective anti-yeast activity against Saccharomyces cerevisiae (S. cerevisiae) strains. Using a combination of chromatographic methods, (-)-trachelogenin (1) and clematoside-S (2) were isolated from this plant for the first time, and their chemical structure was identified by mass spectrometry (MS) and extensive nuclear magnetic resonance (NMR) data analysis. In addition, 1 was found to be inactive against all of the test microorganisms in the antimicrobial assay, whereas 2 exhibits a specific anti-yeast activity against S. cerevisiae strains with diameter of inhibition zones in the range from 11 to 20 mm. Furthermore, the MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 2 against S. cerevisiae strains were detected to be in the ranges of 0.61 to 9.8 µg/mL and 2.42 to 9.8 µg/mL, respectively. This is the first report of 2 with a specific anti-yeast activity. The above result suggests the potential application of U. lobata to be used as a natural anti-yeast agent in food preservation.
Subject(s)
Malvaceae/chemistry , Oleanolic Acid/analogs & derivatives , Saccharomyces cerevisiae/drug effects , Drug Discovery , Ethanol/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Molecular Structure , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Saccharomyces cerevisiae/growth & development , Saponins/chemistry , Saponins/pharmacology , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
CaAFe4As4 with A = K, Rb, and Cs are close to the doped 122 system, and the parent material can reach a superconducting transition temperature of 31-36 K without doping. To study the role of alkali metals, we investigated the induced hole doping and chemical pressure effects as a result of the introduction of alkali metals using density-functional-based methods. These two effects can affect the superconducting transition temperature by changing the number of electrons and the structure of the FeAs conductive layer, respectively. Our study shows that the dxz and dyz orbitals, which are degenerate in CaFe2As2, become nondegenerate in CaAFe4As4 due to two nonequivalent arsenic atoms (As1 and As2). The unusual oblate ellipsoid hole pocket at Γ point in CaAFe4As4 results from a divalent cation Ca2+ replaced by a monovalent cation A+. It shows one of the main differences in fermiology compared to a particular form of CaFe2As2 with reduced 1144 symmetry, due to the enhancement of As2-Fe hybridization. The unusual band appears in CaFe2As2 (1144) and gradually disappears in the change of K to Cs. Further analysis shows that this band is contributed by As1 and has strong dispersion perpendicular to the FeAs layer, suggesting that it is related to the peculiar van Hove singularity below the Fermi level. In addition, various aspects of CaFe2As2 (1144) and CaAFe4As4 in the ground state are discussed in terms of the influence of hole doping and chemical pressure.
ABSTRACT
The superconducting transition temperatures (Tc) of RbGd2Fe4As4O2, RbTb2Fe4As4O2, and RbDy2Fe4As4O2 are 35 K, 34.7 K, and 34.3 K without doping, respectively. For the first time, we have studied the high-temperature nonmagnetic state and the low-temperature magnetic ground state of 12442 materials, RbTb2Fe4As4O2 and RbDy2Fe4As4O2, using first principles calculations and comparing them with RbGd2Fe4As4O2. We also performed a detailed study of the effects of lanthanides and bilayer Fe2As2. We predict that the ground state of RbLn2Fe4As4O2 (Ln = Gd, Tb, and Dy) is spin-density-wave-type, in-plane, striped antiferromagnets, and the magnetic moment around each Fe atom is about 2 µB. We also found that the structural differences caused by the simple ionic radius have little effect on the properties of these three materials. Different lanthanide elements themselves play a major role in the electronic properties of the materials. It can be confirmed that the effect of Gd on RbLn2Fe4As4O2 is indeed different from that of Tb and Dy, and the presence of Gd is more conducive to interlayer electron transfer. This means that Gd can transfer more electrons from the GdO layer to the FeAs layer compared to Tb and Dy. Therefore, RbGd2Fe4As4O2 has a stronger internal coupling strength of the bilayer Fe2As2 layer. This can explain why the Tc of RbGd2Fe4As4O2 is slightly higher than that of RbTb2Fe4As4O2 and RbDy2Fe4As4O2.
ABSTRACT
Aspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid-sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole-cell patch-clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate reduced acidosis-induced membrane depolarization. These data suggest that ASICs in the cortex are molecular targets of high doses of aspirin and salicylate. In addition, the results from lactate dehydrogenase release measurement showed that high doses of aspirin and salicylate protected the cortical neuron from acidosis-induced neuronal injury. These findings may contribute to a better understanding of the therapeutic mechanisms of aspirin and salicylate actions in the brain and provide new evidence on aspirin and salicylate used as neuroprotective agents in the treatment of ischemic stroke.
Subject(s)
Acidosis/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Aspirin/pharmacology , Cerebral Cortex/cytology , Nerve Tissue Proteins/physiology , Neurons/drug effects , Salicylates/pharmacology , Sodium Channels/physiology , Acid Sensing Ion Channels , Animals , Animals, Newborn , Cell Death/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Interactions , Electric Stimulation , Embryo, Mammalian , Neural Inhibition/drug effects , Patch-Clamp Techniques , Propidium , Rats , Rats, Sprague-Dawley , Sodium Channel Blockers/pharmacology , Tetrodotoxin/pharmacologyABSTRACT
The aim of this study was to determine the main constituents of the essential oil isolated from Fortunella crassifolia Swingle peel by hydro-distillation, and to test the efficacy of the essential oil on antimicrobial activity. Twenty-five components, representing 92.36% of the total oil, were identified by GC-MS analysis. The essential oil showed potent antimicrobial activity against both Gram-negative (E. coli and S. typhimurium) and Gram-positive (S. aureus, B. cereus, B. subtilis, L. bulgaricus, and B. laterosporus) bacteria, together with a remarkable antifungal activity against C. albicans. In a food model of beef extract, the essential oil was observed to possess an effective capacity to control the total counts of viable bacteria. Furthermore, the essential oil showed strongly detrimental effects on the growth and morphological structure of the tested bacteria. It was suggested that the essential oil from Fortunella crassifolia Swingle peel might be used as a natural food preservative against bacteria or fungus in the food industry.
Subject(s)
Anti-Infective Agents/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Rutaceae/chemistry , Animals , Bacterial Load , Cattle , Food Microbiology , Food Preservatives/chemistry , Fruit/chemistry , Fungi/drug effects , Gas Chromatography-Mass Spectrometry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Meat/microbiology , Microbial Sensitivity Tests , Microscopy, Electron, TransmissionABSTRACT
In the present study, we firstly compared rat intestinal α-glucosidase inhibitory activity by different ethanol-aqueous extractions from the dried fruits of Terminalia chebula Retz. The enzymatic assay showed that the 80% ethanol extract was more potent against maltase activity than both 50% and 100% ethanol extracts. By HPLC analysis, it was determined that the 80% ethanol extract had a higher content of chebulagic acid than each of 50% or 100% ethanol extract. Next, we investigated how efficiently chebulagic acid could inhibit sugar digestion by determining the glucose level on the apical side of the Caco-2 cell monolayer. The result showed that the maltose-hydrolysis activity was down-regulated by chebulagic acid, which proved to be a reversible inhibitor of maltase in Caco-2 cells. On the other hand, chebulagic acid showed a weak inhibition of sucrose-hydrolysis activity. Meanwhile, chebulagic acid did not have an obvious influence on intestinal glucose uptake and was not effective on glucose transporters. Further animal studies revealed that the oral administration of chebulagic acid (100 mg/kg body weight) significantly reduced postprandial blood glucose levels by 11.1% in maltose-loaded Sprague-Dawley (SD) rats compared with the control group, whereas the oral administration of chebulagic acid did not show a suppressive effect on postprandial hyperglycemia in sucrose- or glucose-loaded SD-rats. The results presented here suggest that chebulagic acid from T. chebula can be used to control blood glucose and manage type 2 diabetes, although clinical trials are needed.
Subject(s)
Benzopyrans/administration & dosage , Fruit/chemistry , Glucosides/administration & dosage , Hyperglycemia/drug therapy , Hypoglycemic Agents/administration & dosage , Plant Extracts/administration & dosage , Terminalia/chemistry , Administration, Oral , Animals , Benzopyrans/pharmacology , Caco-2 Cells , Down-Regulation , Drug Evaluation, Preclinical , Glucosides/pharmacology , Humans , Hyperglycemia/metabolism , Hypoglycemic Agents/pharmacology , Male , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , alpha-Glucosidases/metabolismABSTRACT
Resveratrol, a naturally occurring stilbene found in red wine, is known to modulate the activity of several types of ion channels and membrane receptors, including Ca2+, K+, and Na+ ion channels. However, little is known about the effects of resveratrol on some important receptors, such as glycine receptors and GABAA receptors, in the central nervous system (CNS). In the present study, the effects of resveratrol on glycine receptor or GABAA receptor-mediated currents in cultured rat inferior colliculus (IC) and auditory cortex (AC) neurons were studied using whole-cell voltage-clamp recordings. Resveratrol itself did not evoke any currents in IC neurons but it reversibly decreased the amplitude of glycine-induced current (IGly) in a concentration-dependent manner. Resveratrol did not change the reversal potential of IGly but it shifted the concentration-response relationship to the right without changing the Hill coefficient and with decreasing the maximum response of IGly. Interestingly, resveratrol inhibited the amplitude of IGly but not that of GABA-induced current (IGABA) in AC neurons. More importantly, resveratrol inhibited GlyR-mediated but not GABAAR-mediated inhibitory postsynaptic currents in IC neurons using brain slice recordings. Together, these results demonstrate that resveratrol noncompetitively inhibits IGly in auditory neurons by decreasing the affinity of glycine to its receptor. These findings suggest that the native glycine receptors but not GABAA receptors in central neurons are targets of resveratrol during clinical administrations.
Subject(s)
Inferior Colliculi/drug effects , Neurons/drug effects , Receptors, Glycine/metabolism , Resveratrol/pharmacology , Synaptic Transmission/drug effects , Animals , Inferior Colliculi/metabolism , Neurons/metabolism , Patch-Clamp Techniques , RatsABSTRACT
GABAA receptors (GABAARs) and glycine receptors (GlyRs) are two principal inhibitory chloride ion channels in the central nervous system. The two receptors do not function independently but cross-talk to each other, i.e., the activation of one receptor would inhibit the other. This cross-talk is present in different patterns across various regions in the central nervous system; however, the factor that determines these patterns is not understood. Here, we show that the pattern of cross-talk between the two receptors is shaped by their relative expression level in a neuron: a higher expression level correlates with louder talk. In line with a tendency of decrease in expression level of GlyRs and increase in expression level of GABAARs from the spinal cord, the brainstem to the neocortex, GlyRs talked much louder (i.e. produced greater inhibition) than GABAARs (one-way pattern) in spinal cord neurons, about equally loud as GABAARs (symmetric pattern) in inferior colliculus neurons and less loud (i.e. less inhibition) than GABAARs (asymmetric pattern) in auditory cortex neurons. Overexpression of GlyRs in inferior colliculus neurons produced an asymmetric pattern that should otherwise have been observed in spinal cord neurons. These expression level-dependent patterns of cross-talk between the two receptors may suggest how the central nervous system uses an alternative mechanism to maintain a delicate level of inhibition through adjusting the proportion of the two receptors in a neuron along its pathway.
Subject(s)
Neurons/metabolism , Receptors, GABA-A/metabolism , Receptors, Glycine/metabolism , Spinal Cord/metabolism , Animals , Auditory Cortex/metabolism , Cells, Cultured , Inferior Colliculi/metabolism , Patch-Clamp Techniques , RatsABSTRACT
We examined the physical properties of the quasi-one-dimensional superconductor Ta4Pd3Te16 in the normal state by detailed measurements of susceptibility, in-plane anisotropic resistivity, magnetoresistance, Hall resistivity, and Seebeck coefficient. The large Wilson ratio, as inferred from normal-state susceptibility, indicates strong electron-electron interaction. The Hall and Seebeck coefficients show not only significant temperature-dependent behavior, indicating the multiband effect, but also an obvious anomaly around T 1 = 40 K. Analyses of both the Hall resistivity and thermopower using a two-band model indicate that the electrons dominate the electrical transport at low temperatures. Our results imply that it is the quantum fluctuations of the charge order taking place in the temperature range 30-50 K that may result in the abnormal normal-state properties of Ta4Pd3Te16.
ABSTRACT
The antibiofilm activity and molecular mechanism of a natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA) against Staphylococcus aureus were investigated in this study. Crystal violet staining and XTT reduction assay demonstrated that CHQA could prominently prevent the biofilm formation of S. aureus accompanied with decrease in metabolic activity of biofilm cells. Meanwhile, microscopic observations revealed that CHQA caused a huge collapse on the architecture of S. aureus biofilm. Moreover, CHQA specifically inhibited the initial attachment phase of biofilm development and reduced S. aureus adhesion to fibrinogen. Fluorescence resonance energy transfer assay and molecular simulation showed that CHQA inhibited the activity of S. aureus sortase A (SrtA) through binding to the active region via non-covalent interactions. Additionally, CHQA efficiently reduced S. aureus attachment to stainless steel. Hence, these results suggested CHQA as a potential bacterial biofilm inhibitor which achieved antibiofilm activity through affecting the attachment phase of biofilm formation by targeting SrtA.
ABSTRACT
Available evidence suggests that sodium salicylate (SS) may produce tinnitus through altering the balance between inhibition and excitation in the central auditory system. Since serotonin (5-hydroxytryptamine, 5-HT) containing fibers preferentially innervate inhibitory GABA neurons, there exists a possibility that SS causes the imbalance between inhibition and excitation through influencing serotonergic modulation of the GABAergic synaptic transmission. In the present study, we examined the effects of SS on 5-HT-mediated GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) from neurons of the central nucleus of rat inferior colliculus with whole-cell patch-clamp technique and brain slice preparation. Perfusion of 40 microM 5-HT robustly enhanced both frequency and amplitude of GABAergic sIPSCs and this 5-HT-induced enhancement of GABAergic sIPSCs could be suppressed by 1.4mM SS. Tetrodotoxin at 0.5 microM produced a similar effect as SS did, suggesting that SS suppresses the 5-HT-induced enhancement of GABAergic sIPSCs through depressing spontaneous action potentials of GABA neurons. Our findings suggest that SS may preferentially target GABA neurons and consequently interrupt a normal level of GABAergic synaptic transmissions maintained by the serotonergic system in SS-induced tinnitus.
Subject(s)
Inferior Colliculi/drug effects , Inferior Colliculi/physiology , Inhibitory Postsynaptic Potentials/drug effects , Serotonin/pharmacology , Sodium Salicylate/toxicity , gamma-Aminobutyric Acid/physiology , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Auditory Perception/drug effects , Auditory Perception/physiology , Female , In Vitro Techniques , Inhibitory Postsynaptic Potentials/physiology , Male , Models, Neurological , Patch-Clamp Techniques , Rats , Rats, Sprague-Dawley , Serotonin/analogs & derivatives , Tetrodotoxin/toxicity , Tinnitus/chemically induced , Tinnitus/physiopathologyABSTRACT
Chebulagic acid, isolated form Terminalia chebula Retz, proved to be a reversible and non-competitive inhibitor of maltase with a K(i) value of 6.6 muM. The inhibitory influence of chebulagic acid on the maltase-glucoamylase complex was more potent than on the sucrase-isomaltase complex. The magnitude of alpha-glucosidase inhibition by chebulagic acid was greatly affected by its origin. These results show a use for chebulagic acid in managing type-2 diabetes.
Subject(s)
Benzopyrans/pharmacology , Enzyme Inhibitors/pharmacology , Glucosides/pharmacology , Glycoside Hydrolase Inhibitors , Animals , RatsABSTRACT
Methanolic extracts from the medicinal parts of 40 traditional Chinese herbs were tested in screening experiments for rat intestinal α-glucosidase. The methanolic extract from the leaves of Adhatoda vasica Nees (Acanthaceae) showed the highest sucrase inhibitory activity with sucrose as a substrate. Enzyme assay-guided fractionation of this extract afforded vasicine (1) and vasicinol (2), and the structures of these compounds were elucidated on the basis of MS and NMR analysis. Compounds 1 and 2 showed a high sucrase inhibitory activity, and the IC50 values were 125µM and 250µM, respectively. Both 1 and 2 were shown to be reversible inhibitors of sucrase. Kinetic data revealed that compounds 1 and 2 inhibited sucrose-hydrolysing activity of rat intestinal α-glucosidase competitively with Ki values of 82µM and 183µM, respectively. This is the first report on the mammalian α-glucosidase inhibition of A. vasica and the inhibitory effect on sucrase by 1 and 2 from this herb species. These results suggest a use of the extract of A. vasica as an antidiabetic agent and show a possibility that compounds 1 and 2 could be an useful treatment for metabolic disorders.
ABSTRACT
INTRODUCTION: It is known that an interruption of acoustic input in early life will result in abnormal development of the auditory system. Here, we further show that this negative impact actually spans beyond the auditory system to the hippocampus, a system critical for spatial memory. METHODS: We induced a temporary conductive hearing loss (TCHL) in P14 rats by perforating the eardrum and allowing it to heal. The Morris water maze and Y-maze tests were deployed to evaluate spatial memory of the rats. Electrophysiological recordings and anatomical analysis were made to evaluate functional and structural changes in the hippocampus following TCHL. RESULTS: The rats with the TCHL had nearly normal hearing at P42, but had a decreased performance with the Morris water maze and Y-maze tests compared with the control group. A functional deficit in the hippocampus of the rats with the TCHL was found as revealed by the depressed long-term potentiation and the reduced NMDA receptor-mediated postsynaptic current. A structural deficit in the hippocampus of those animals was also found as revealed the abnormal expression of the NMDA receptors, the decreased number of dendritic spines, the reduced postsynaptic density and the reduced level of neurogenesis. CONCLUSIONS: Our study demonstrates that even temporary auditory sensory deprivation in early life of rats results in abnormal development of the hippocampus and consequently impairs spatial memory in adulthood.