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ABSTRACT: Total ginsenosides have been shown to have therapeutic actions as antidepressants. We report a major active ingredient of total ginsenosides, the ginsenoside Rb3 (Rb3), which may have antidepressant-like effects. Using the forced swim test, tail suspension test, and learned helplessness procedure, we found that Rb3 had significant anti-immobility effects in mice in the forced swim and tail suspension tests and reduced the number of escape failures in the learned helplessness procedure. In a reserpine-induced syndrome model, Rb3 attenuated hypothermia, palpebral ptosis, and akinesia. In the chronic mild stress model, chronic Rb3 administration reversed the decrease in locomotor activity, novelty-suppressed feeding, and sucrose preference. Furthermore, neurochemical tests were performed to support our hypothesis that biochemical variations (i.e. brain-derived neurotrophic factor and the monoamine neurotransmitters 5-hydroxytryptamine, dopamine, and norepinephrine) are involved in Rb3's antidepressant-like effects. Finally, we found, using whole-cell patch-clamp recordings, that the action potential transmission in neurons within the somatosensory cortex was excited by Rb3 perfusion and blocked with Panax notoginseng total saponins extracted from leaves. This study provides evidence for the mechanism of action of the antidepressant-like effects of Rb3.
Journal of Psychopharmacology 09/2011; 26(5):697-713. · 3.04 Impact Factor
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ABSTRACT: Seamoth (Pegasus laternarius Cuvier) is extensively used to treat various diseases on the coastland of Guangdong Province in China, such as scrofula, cough, and diarrhea. The total extract of Pegasus laternarius (EP) was subjected to column chromatography to acquire three different constituents (EPC1, EPC2, and EPC3). Cerebral neuron injury was induced by glutamate, H₂O₂, and serum deprivation. After treating with or without different extracts, cell viability was assessed with the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and cell apoptosis was analyzed with Hoechst 33258 staining and agarose gel electrophoresis. We also determined the levels of lactate dehydrogenase (LDH), maleic dialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The results showed that both EP and EPC2 promoted the outgrowth of cultural neurons, increased antioxidant enzyme activity, and protected neurons from neuronal injury or apoptosis induced by glutamate, H₂O₂, and serum deprivation. EPC1 and EPC3 had little or no effect on neurons. These results suggest that the active ingredients obtained from Pegasus laternarius have potential neuroprotective effects on injured neurons by promoting the outgrowth of cultured neurons, increasing the activity of intracellular antioxidants, and exerting antiapoptotic effects. This neuroprotection may be attributable to specific active ingredients, such as taurine, novel ceramide, and cholesterol.
Cellular and Molecular Neurobiology 01/2011; 31(1):73-82. · 1.97 Impact Factor
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ABSTRACT: Total saponins extracted from the caudexes and leaves of Panax notoginseng (SCLPN) have been used in the clinic for improving mental function, treating insomnia, and alleviating anxiety. The present study evaluated the potential antidepressant activity of SCLPN in rodent models of depression and the mechanism of action of SCLPN. Mice were received SCLPN at doses of 10-1000 mg/kg daily for 1, 7, and 14 days and then were subjected to the forced swim test and locomotor activity test. The results showed that SCLPN decreased immobility time in the forced swim test, with little effect on locomotion. In the chronic mild stress model, chronic SCLPN treatment (70 mg/kg) reversed the rats' depression-like behavior. Furthermore, SCLPN exerted its antidepressant-like effect by increasing the levels of 5-hydroxytryptamine, dopamine, and noradrenaline. Additionally, SCLPN treatment reduced intracellular Ca(2+) in cultured neurons. The present study suggests that SCLPN may function as an antidepressant, and the antidepressant-like effects of SCLPN may be mediated by modulation of brain monoamine neurotransmitters and intracellular Ca(2+) concentration.
Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2011; 18(8-9):731-8. · 2.17 Impact Factor
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ABSTRACT: The fruit hull of Garcinia mangostana L. contains oxygenated and prenylated phenol derivatives, such as xanthones or xanthen-9H-ones, and is used by people in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, suppuration, and chronic ulcer. We isolated the active ingredients from the crude ethanol extract of G.mangostana L. (CEM) and investigated their analgesic effects and underlying mechanisms. CEM at intragastric (i.g.) doses of 0.5, 1, and 3 g/kg clearly exhibited antinociceptive effects in the hot-plate and acetic acid-induced writhing tests in mice. Two isolated compounds, alpha-mangostin and gamma-mangostin, exhibited analgesic effects at doses of 25 and 50 mg/kg (i.g.) in the hot-plate and formalin tests, respectively. CEM at doses of 0.5, 1, and 3 g/kg significantly inhibited xylene-induced release of inflammatory mediators. CEM, alpha-mangostin, and gamma-mangostin each dose-dependently demonstrated the ability to scavenge reactive oxygen species. In conclusion, our results demonstrate that CEM and mangostins possess potent peripheral and central antinociceptive effects in mice and suggest that xanthones may be developed as novel analgesics and anti-inflammatory drugs.
Pharmacology Biochemistry and Behavior 04/2010; 95(2):166-72. · 2.53 Impact Factor
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ABSTRACT: The developmental profile of the firing patterns and construction of synapse connection were studied in LTS interneurons of prefrontal cortex (PFC) in rats with age (from P7 to P30). We used whole cell patch-clamp recordings to characterize electrophysiological properties of LTS interneurons in PFC at different age stages, including the action potentials (APs), short-term plasticity (STP), evoked excitatory postsynaptic currents (eEPSCs), spontaneous excitatory postsynaptic currents (sEPSC), and spontaneous inhibitory postsynaptic current (sIPSC). The developmental profile of LTS interneurons in our research showed two phases changes. The early phase from P7-P11 to P16-P19 during which the development of individual LTS interneuron dominated and just some simple synaptic connections formed, the synaptic inputs from pyramidal cells play a promoting role for the maturation of LTS interneurons to some extent. This was based on the changes of APs, eEPSCs, and STP such as the curtailment of time course of APs, the increasing facilitation of STP before P16-P19 group. The late phase from P20-P23 to P > 27 during which the function of inhibitory cortex network enhanced and the characters of this inhibitory cortex network continually changed although in the oldest age group (P > 27) in our research. The frequency and amplitude of sIPSC showed continually changes, and at the same age group, the frequency ratios and amplitude ratios of sIPSC was higher than that of sEPSC. Our study showed a foundation to clarify mechanisms underlying the evolution in time of intrinsic neuronal membrane properties and their important roles in balancing the cortex network, providing an academic foundation for the pathological researching on some psychiatric and neurological disorders.
Cellular and Molecular Neurobiology 11/2009; 30(4):543-55. · 1.97 Impact Factor
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ABSTRACT: Four recombinant neurotoxins Hk2a, Hk7a, Hk8a, Hk16a, originally from a sea anemone species Anthopleura sp., were obtained by fusion expression of their genes in Escherichia coli. These neurotoxins were composed of 47 amino acid residues, among which the differences were found at positions 14, 22, 25, and 37, respectively. The effects of the four neurotoxins on single-channel current of sodium in rat hippocampal neurons were studied by cell-attached patch clamp. Each neurotoxin 2 microM could modulate the sodium channel by prolonging the opening dwell time and increasing the open probability, but did not change the amplitude of sodium channel currents. Based on the studies of the structure-function relationship, we found that Hk7a displayed the biggest increase of the open probability because His14 (from Arg14) makes its structure seem more compact in comparison with the other three toxins and Ap-A. Phe25 (Hk8a, Hk16a), which varied from Ala25 (Hk2a, Hk7a), showed that phenyl group might interfere with other key amino acid residue to decrease the activity of toxins. Arg37 (from His37) in Hk8a contributed to decrease of open probability. In our work, it was shown that these important amino acid sites might provide a reliable proof for the future pharmaceutical design.
Journal of Biochemical and Molecular Toxicology 09/2009; 23(4):244-55. · 1.38 Impact Factor
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ABSTRACT: The developmental changes of the sodium channel and construction of synapse connection were studied in cerebral cortical pyramidal neurons of rats at different age groups. We used whole-cell patch-clamp recordings to characterize electrophysiological properties of cortical neurons at different age stages, including the sodium currents, APs evoked by depolarizing current and short-term plasticity of the eEPSCs. The result shows that the sodium currents undergo a hyperpolarizing shift in activation process and acceleration of activation and inactivation with age. The maximal sodium current also increased with maturation, and the evident difference appeared from P7-P11 (with the day of birth as P0) to P12-P15 group. The tendency of the sodium current density changes which exhibited the same properties as that of sodium current, showed the significant increases from P19-P21 to P >or= 22 group. The APs' parameters exhibited the age-dependent changes except the threshold, including the increase of the peak amplitude from P <or= 6 to P16-P18 groups, and the curtailment of duration and the time-to-peak with age. The amplitude of 1st eEPSC increased with maturation, and STP displays depression at all observed groups. In addition, although STP also exhibited depression in response to last three stimulations in P >or= 22 group, the 2nd response showed the tendency of facilitation compared with the younger age groups. Our results indicated that the cerebral cortical pyramidal neurons of rats are undergoing marked changes in the characteristics of their sodium channels with maturation, which play a critical role in synaptogenesis and construction of the neuronal network.
Cellular and Molecular Neurobiology 05/2009; 29(8):1131-42. · 1.97 Impact Factor
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ABSTRACT: The present study investigated the effects of dopamine on chloride transport across cultured rat caudal epididymal epithelium. The results showed that dopamine induced a biphasic short-circuit current (Isc) in a concentration-dependent manner. The dopamine-induced response consisted of an initial rapid spike followed by a sustained phase. The alpha and beta adrenoreceptor inhibitors, phentolamine and propranolol, inhibited the initial spike and the sustained phase, respectively, suggesting a contribution of adrenergic receptors. The response was almost abolished by removing the extracellular Cl-, suggesting that the dopamine-induced short-circuit current is primarily a Cl- current. The response was inhibited by the apical Cl- channel blocker, diphenylamine-dicarboxylic acid, and the Ca2+-activated Cl- channel blocker, disulfonic acid stilbene, indicating that Cl- may pass through two types of Cl- channels on the apical side. Preloading monolayers with the intracellular Ca2+ chelator BAPTA/AM abolished the initial spike and greatly reduced the second phase in the Isc response to dopamine. Pretreating the monolayers with an adenylate cyclase inhibitor, MDL12330A, inhibited all of the second Isc response and part of the initial spike. Also, characteristics of the Cl- currents induced by dopamine were observed in whole-cell patch-clamp recording. The increases of intracellular cAMP and Ca2+ induced by dopamine were also measured. The results suggest that extracellular dopamine activates Ca2+-dependent and cAMP-dependent regulatory pathways, leading to activation of both Ca2+-dependent and cAMP-dependent Cl- conductances in epididymal epithelial cells.
Biology of Reproduction 10/2008; 80(1):13-23. · 4.01 Impact Factor
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ABSTRACT: A novel conotoxin named lt6c, an O-superfamily conotoxin, was identified from the cDNA library of venom duct of Conus litteratus. The full-length cDNA contains an open reading frame encoding a predicted 22-residue signal peptide, a 22-residue proregion and a mature peptide of 28 amino acids. The signal peptide sequence of lt6c is highly conserved in O-superfamily conotoxins and the mature peptide consists of six cysteines arranged in the pattern of C-C-CC-C-C that is defined the O-superfamily of conotoxins. The mature peptide fused with thioredoxin, 6-His tag, and a Factor Xa cleavage site was successfully expressed in Escherichia coli. About 12 mg lt6c was purified from 1L culture. Under whole-cell patch-clamp mode, lt6c inhibited sodium currents on adult rat dorsal root ganglion neurons. Therefore, lt6c is a novel O-superfamily conotoxin that is able to block sodium channels.
Journal of Peptide Science 10/2008; 14(10):1077-83. · 1.80 Impact Factor
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ABSTRACT: We have investigated the action of the recombinant neurotoxins, named Hk7a and Hk2a, whose amino acid sequences differ only in two positions, isolated from the sea anemone Anthopleura sp., on neuronal sodium currents using the whole-cell voltage-clamp techniques. The rat cerebral cortical neurons in primary culture were used for this study. In our experiments, these cells all express tetrodotoxin-sensitive (TTX-S) sodium currents. Under the voltage-clamp condition, application of Hk7a and Hk2a reduced the sodium channel current amplitude and shifted the voltage dependence of activation to more positive potential; while Hk7a produced no significant effect on the voltage at which 50% of the channels were inactivated, Hk2a caused profound hyperpolarizing shift of the voltage-dependent inactivation. Also, both Hk7a and Hk2a increased the time course of recovery from inactivation. In kinetic studies, whereas application of Hk2a slows the time to peak of voltage-gated sodium channel, the time course of fast and slow inactivating component, no significant effect was observed in Hk7a. These results suggested that the difference of key amino acid between Hk7a and Hk2a might contribute to their different action; therefore, they could be used as pharmacological tool to study the structure and function of voltage-gated sodium channel.
Cellular and Molecular Neurobiology 07/2008; 28(8):1119-28. · 1.97 Impact Factor
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ABSTRACT: In the present study, the intracellular regulatory pathways involved in the adrenalin-stimulated chloride secretion across T84 cells were investigated. Biphasic characteristics were observed in the Isc response to the basolateral addition of adrenalin (0.25 nM-100 microM). The biphasic response was almost abolished by removing ambient Cl(-). Chloride secretion was found to depend on the activities of basolaterally located Na+-K+-2Cl(-) cotransporters and K+ channels. The alpha-adrenoceptor antagonist phentolamine did not have any effect on either phase of adrenalin-induced Isc, while after pretreatment of the beta-adrenoceptor antagonist propranolol, the adrenalin-induced Isc was substantially abolished, suggesting the biphasic response may be mediated by the beta-adrenoceptor. Under whole cell patch-clamp conditions, T84 cells responded to adrenalin with a rise in inward current. The current, which exhibited a linear I-V relationship and time- and voltage-independent characteristics, was inhibited by the chloride channel blocker DPC and the reverse potential was close to the equilibrium potential for Cl(-) (0 mV), implying that the current was Cl(-) selective. When preloaded with a Ca2+-chelating agent, BAPTA/AM did not affect the Isc response to adrenalin, whereas the Isc was destroyed by pretreating the cells with an adenyl cyclase inhibitor, MDL12330A. These observations were further supported by the intracellular [cAMP] measurement experiment, indicating that adrenalin induced chloride secretion could be mediated by a beta-adrenoceptor only involving cAMP as an intracellular second messenger.
Cell Biology International 07/2008; 32(6):679-87. · 1.48 Impact Factor
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ABSTRACT: Neurotransmitter-controlled Cl- secretions play an important role in maintenance of the epididymal microenvironment for sperm maturation. This study was carried out to investigate the effect of carbachol (CCH) on the cultured rat epididymal epithelium and the signal transduction mechanisms of this response. In normal K-H solution, CCH added basolaterally elicited a biphasic Isc response consisting of a transient spike followed by a second sustained response. Ca2+ activated Cl- channel blocker disulfonic acid stilbene (DIDS, 300 microM) only inhibited part of the CCH-induced Isc response, while nonselective Cl- channel blocker diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced all, indicating the involvement of different conductance pathways. Both peaks of the CCH-induced Isc response could be significantly inhibited by pretreatment with an adenylate cyclase inhibitor, MDL12330A (50 microM). An increase in intracellular cAMP content upon stimulation of CCH was measured. All of the initial peak and part of the second peak could be inhibited by pretreatment with Ca2+-chelating agent BAPTA/AM (50 microM) and an endoplasmic reticulum Ca2+ pump inhibitor, Thapsigagin (Tg, 1 microM). In a whole-cell patch clamp experiment, CCH induced an inward current in the single cell. Two different profiles of currents were found; the first component current exhibited an outward rectifying I-V relationship in a time and voltage-dependent manner, and the current followed showed a linear I-V relationship. The carbachol-induced current was found to be partially blockable by DIDS and could be completely blocked by DPC. The above results indicate that the CCH-induced Cl- secretion could be mediated by Ca2+ and cAMP-dependent regulatory pathways.
Biology of Reproduction 10/2006; 75(3):407-13. · 4.01 Impact Factor
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ABSTRACT: The aim of our present study was to investigate the short-circuit current response to carbachol in cultured rat cauda epididymal epithelia and the signal transduction mechanisms involved. Carbachol added basolaterally induced a concentration-dependent increase in short-circuit current (Isc) across the epididymal epithelium consisting of a rapidly rising phase and a long term sustained response. The response was almost abolished by removing Cl(-) from the extracellular medium and blockable by pretreating the tissues with DPC, indicating a substantial contribution of Cl(-) secretion to the carbachol-induced response. The muscarinic acetylcholine receptor antagonist atropine inhibited the response, but the nicotinic acetylcholine receptors antagonist curarine had no effect, suggesting that only the muscarinic acetylcholine receptors mediated the secretory response of the basolateral side of rat cauda epididymal epithelium to carbachol. Addition of carbachol to the apical side of the tissue was found not to elicit an Isc response. These results suggested that muscarinic receptors are present in the basolateral side of rat cauda epididymal epithelium. Activation of these receptors by acetylcholine released from the nerve endings regulates epididymal transepithelial Cl(-) secretion. Cholinergic stimulation therefore contributes to the formation of luminal fluid microenvironment.
Cell Biology International 10/2006; 30(9):741-6. · 1.48 Impact Factor
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ABSTRACT: To study the lipid peroxidation products level in aged animals central nerve system and the antioxidation effect of the methol extract from Pegasus laternarius.
The lipid peroxidation product MDA was tested by spectrophotometer.
Compared with the 10 month-old guinea pig, the MDA in 32 month-old guinea pig central nerve system obviously elevated, there were some difference in different fields of tested guinea pig brain, the level of MDA in hypothalamus increased biggest (up to 161.7%), cerebral cortex 93.7%, cerebella 84.9%, brain stem 81.2%, spinal cord 90.7%, rest of the cerebrum 58.9%. The method extract from Pegasus laternarius 10, 20, 40 mg/kg and ginseng saponin 20 mg/kg could reduce the level of MDA in tested brain field of aged animals. The method extract from Pegasus laternarius had stronger activity in brain stem, spinal cord and hypothalamus.
The lipid peroxidation in aged animal may be increased, the method extract from Pegasus laternarius and ginseng saponin have a protective effect on neuron in central nerve system of aged animals from free radical hurt.
Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 05/2002; 25(4):275-7.
