Objective To probe into the protective mechanism of electro-acupuncture （EA） on anti-oxygen stress in dementia-model rats. Methods A total of 30 male SD rats of cleaning grade were randomized into three groups, name...Objective To probe into the protective mechanism of electro-acupuncture （EA） on anti-oxygen stress in dementia-model rats. Methods A total of 30 male SD rats of cleaning grade were randomized into three groups, named sham-operation （n = 10）, model （n = 10）, model＋ EA （n = 10）. The dementia-model rat was made with hippocampal GA1 lesions by quinolinic acid （QA）. On the second day of modeling, in model＋ EA group, EA （3 Hz, 2-4 mA, continuous waves） was applied to ＂Dàzhuī＂ （大椎 GV 14） and ＂Shènshū＂ （肾俞 BL 23） for 10 min. The capability of learning and memory was evaluated by step-down test to observe the changes of nitric oxide （NO）, nitric oxide synthase （NOS） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） of the hippocampal tissues in rats separately by biochemical methods. Results EA improved learning and memory of dementia rats with hippocampal CA1 lesions induced by QA at different degrees. It significantly increased SOD activity, reduced MDA content and improved NO level and NOS activity. Conclusion EA improves significantly the learning and memory of the dementia rats due to hippocampal CA1 lesions induced by QA, which is probably relevant with the anti-oxygen stress of EA.展开更多
Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-indu...Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs,and analyzed the role of QA in otitis media with effusion(OME)-induced sensorineural hearing loss(SNHL).After culture in vitro for 72 h,SGCs were exposed to different media and divided into 4 groups:the blank control group,the QA injury group,the MK-801 treatment group,and the MgCl2 protection group.The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later.SGCs were cultured in vitro for 72 h and divided into four groups:the low concentration QA group,the high concentration QA group,the MK-801 group,the MgCl2 group.The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy.Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group(both P0.05).In high concentration QA group,there was an obvious increase of the intracellular calcium concentration in SGCs,which didn’t present in low concentration QA group.In MgCl2 group,the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened,but the intracellular calcium concentration in SGCs had no significant change in MK-801 group.It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane,which might be the mechanism by which OME induced SNHL,while Mg2+ could protect the SCGs from the neurotoxicity of QA.展开更多
Quinolinic acid is a neurotoxic substance produced by tryptophan through the kynurenine metabolism pathway.Quinolinic acid is involved in the pathological processes of Alzheimer's disease,Parkinson's disease,H...Quinolinic acid is a neurotoxic substance produced by tryptophan through the kynurenine metabolism pathway.Quinolinic acid is involved in the pathological processes of Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,encephalitis,depression,and schizophrenia.The above process is realized through pathophysiological processes such as excitatory neurotoxicity,metabolic damage,free radical generation and oxidative stress,participation in inflammatory response,induction of neuron and astrocytic apoptosis.This article will explain the metabolic regulation,biological characteristics,and neurotoxicity of quinolinic acid.The research progress of quinolinic acid in Alzheimer's disease,Parkinson's disease,Huntington's disease,depression and subacute sclerosing panencephalitis is also described.展开更多
The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular an...The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.展开更多
A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under m...A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.展开更多
Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilide...Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilides 2 in boiling DMF, to give the target 3. Decarboxylation of 3 produced 6-fluoro-2-phenyl-3-(substituted amino)-keto-quinolines 4, while that reaction underwent refluxing, afforded 7-fluoro-1-(aryl)-3-phenyl-pyrrolo[3,4-c] quinoline-2,9-diones 5. Structure of the products has been established from their elemental and spectral analysis. All targets exhibited a high to moderate activity against some Aspergillus fungi as amylolytic agents.展开更多
A simple and efficient method for the synthesis of 2-sulfonylquinoline from deoxygenative C2-sulfonylation of quinoline N-oxides with sulfinic acid induced by visible light is presented.This protocol shows a broad sub...A simple and efficient method for the synthesis of 2-sulfonylquinoline from deoxygenative C2-sulfonylation of quinoline N-oxides with sulfinic acid induced by visible light is presented.This protocol shows a broad substrate scope,and desired products with various substituents can be formed in moderate to high yields at room temperature.展开更多
Two novel mononuclear complexes with 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L）, namely, HgLBr2 1 and CuL2Cl2 2, have been prepared by solvothermal reaction of（5-chloro-quinolin-8-yloxy）acetic acid w...Two novel mononuclear complexes with 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L）, namely, HgLBr2 1 and CuL2Cl2 2, have been prepared by solvothermal reaction of（5-chloro-quinolin-8-yloxy）acetic acid with HgBr2 and CuCl2, respectively. Their structures were characterized by IR, elemental analysis, UV-Vis-NIR spectra, TG and single-crystal X-ray diffraction analysis. Interestingly,（5-chloro-quinolin-8-yloxy）acetic acid is changed as 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L） in complexes 1 and 2. Crystal data for 1： C12H10Br2 Cl Hg NO3, Mr = 612.07, triclinic, space group P1 with a = 8.5983（7）, b = 9.7726（6）, c = 10.1549（6） A, α = 66.355（6）, β = 77.067（8）, γ = 78.803（8）°, V = 756.6（9）A^3, Z = 2, Dc = 2.687 g/cm^3, F（000） = 560, μ = 15.633 mm^-1, R = 0.0351 and w R = 0.0504. Crystal data for 2： C24H20Cl4 Cu N2O6, Mr = 637.76, triclinic, space group P1 with a = 10.5324（9）, b = 11.2377（16）, c = 12.0143（12） ？, α = 83.413（11）, β = 64.475（9）, γ = 83.144（11）°, V = 1270.9（2） ？3, Z = 2, Dc = 1.667 g/cm3, F（000） = 646, μ = 1.324 mm-1, R = 0.0408 and wR = 0.0922. In 1, the HgII centre is a distorted trigonal planar geometry comprised of two Br atoms and one quinoline N atom of L. Intermolecular π-π, C–H…π stacking interactions and intermolecular C–H…Br hydrogen bonds are observed in the molecular packing of 1. In complex 2, each CuII center has a distorted octahedral geometry comprised of two chloride ions, two quinoline N atoms and two O atoms of two L ligands. Intermolecular C–H…Cl hydrogen bonds exist in the molecular packing of 2. The fluorescence emission peak of complexes 1 and 2 appears near 406 and 410 nm, respectively. Optical diffuse-reflection spectral results suggest complex 1 has the property of semiconductor.展开更多
基金a grant from the National Natural Science Foundation of China ( No.30772836)Education Bureau,Jiangsu Province (06KJD360146)
文摘Objective To probe into the protective mechanism of electro-acupuncture （EA） on anti-oxygen stress in dementia-model rats. Methods A total of 30 male SD rats of cleaning grade were randomized into three groups, named sham-operation （n = 10）, model （n = 10）, model＋ EA （n = 10）. The dementia-model rat was made with hippocampal GA1 lesions by quinolinic acid （QA）. On the second day of modeling, in model＋ EA group, EA （3 Hz, 2-4 mA, continuous waves） was applied to ＂Dàzhuī＂ （大椎 GV 14） and ＂Shènshū＂ （肾俞 BL 23） for 10 min. The capability of learning and memory was evaluated by step-down test to observe the changes of nitric oxide （NO）, nitric oxide synthase （NOS） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） of the hippocampal tissues in rats separately by biochemical methods. Results EA improved learning and memory of dementia rats with hippocampal CA1 lesions induced by QA at different degrees. It significantly increased SOD activity, reduced MDA content and improved NO level and NOS activity. Conclusion EA improves significantly the learning and memory of the dementia rats due to hippocampal CA1 lesions induced by QA, which is probably relevant with the anti-oxygen stress of EA.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30872866)
文摘Our study investigated the neurotoxicity of quinolinic acid(QA) to spiral ganglion cells(SGCs),observed the protective effects of N-methyl-D-aspartate(NMDA) receptor antagonist MK-801 and magnesium ions on the QA-induced injury to SGCs,and analyzed the role of QA in otitis media with effusion(OME)-induced sensorineural hearing loss(SNHL).After culture in vitro for 72 h,SGCs were exposed to different media and divided into 4 groups:the blank control group,the QA injury group,the MK-801 treatment group,and the MgCl2 protection group.The apoptosis rate of SGCs was analyzed by Annexin V and PI double staining under the fluorescence microscopy 24 h later.SGCs were cultured in vitro for 72 h and divided into four groups:the low concentration QA group,the high concentration QA group,the MK-801 group,the MgCl2 group.The transient changes of intracellular calcium concentration were observed by the laser scanning confocal microscopy.Apoptosis rate in QA injury group was higher than that in blank control group and MgCl2 protection group(both P0.05).In high concentration QA group,there was an obvious increase of the intracellular calcium concentration in SGCs,which didn’t present in low concentration QA group.In MgCl2 group,the peak values of the intracellular calcium concentration in SGCs were reduced and the duration was shortened,but the intracellular calcium concentration in SGCs had no significant change in MK-801 group.It was concluded that QA could injure SGCs by excessively activating NMDA receptors on the cell membrane,which might be the mechanism by which OME induced SNHL,while Mg2+ could protect the SCGs from the neurotoxicity of QA.
基金Key R&D Projects of Shanxi Province(No.201803D31129)
文摘Quinolinic acid is a neurotoxic substance produced by tryptophan through the kynurenine metabolism pathway.Quinolinic acid is involved in the pathological processes of Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,encephalitis,depression,and schizophrenia.The above process is realized through pathophysiological processes such as excitatory neurotoxicity,metabolic damage,free radical generation and oxidative stress,participation in inflammatory response,induction of neuron and astrocytic apoptosis.This article will explain the metabolic regulation,biological characteristics,and neurotoxicity of quinolinic acid.The research progress of quinolinic acid in Alzheimer's disease,Parkinson's disease,Huntington's disease,depression and subacute sclerosing panencephalitis is also described.
基金supported by the National Natural Science Foundation of China,Nos.82271327 (to ZW),82072535 (to ZW),81873768 (to ZW),and 82001253 (to TL)。
文摘The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.
基金the National Basic Research Program(No.2003CB515400),administered by the Ministry of Science and Technology of China.
文摘A facile and efficient method for the preparation of 2-non-substituted quinoline-4-carboxylic acids is described via the Pfitzinger reaction of isatins with sodium pyruvate following consequent decarboxylation under microwave irradiation.
文摘Highly efficient syntheses of novel fluorine bearing quinoline-4-carboxylic acids and the related compounds had been achieved from cyclocondensation of 2-amino-5-fluorophenyl glyoxylic acid 1 with benzoyle asetanilides 2 in boiling DMF, to give the target 3. Decarboxylation of 3 produced 6-fluoro-2-phenyl-3-(substituted amino)-keto-quinolines 4, while that reaction underwent refluxing, afforded 7-fluoro-1-(aryl)-3-phenyl-pyrrolo[3,4-c] quinoline-2,9-diones 5. Structure of the products has been established from their elemental and spectral analysis. All targets exhibited a high to moderate activity against some Aspergillus fungi as amylolytic agents.
基金supported by the National Natural Science Foundation of China (21402103, 21772107)the China Postdoctoral Science Foundation (150030)+1 种基金the Research Fund of Qingdao Agricultural University’s Highlevel Person (631303)Shandong province key research and development plan(GG201809130228)~~
文摘A simple and efficient method for the synthesis of 2-sulfonylquinoline from deoxygenative C2-sulfonylation of quinoline N-oxides with sulfinic acid induced by visible light is presented.This protocol shows a broad substrate scope,and desired products with various substituents can be formed in moderate to high yields at room temperature.
基金Supported by Key Laboratory of Organic Synthesis of Jiangsu Province(KJS1308)
文摘Two novel mononuclear complexes with 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L）, namely, HgLBr2 1 and CuL2Cl2 2, have been prepared by solvothermal reaction of（5-chloro-quinolin-8-yloxy）acetic acid with HgBr2 and CuCl2, respectively. Their structures were characterized by IR, elemental analysis, UV-Vis-NIR spectra, TG and single-crystal X-ray diffraction analysis. Interestingly,（5-chloro-quinolin-8-yloxy）acetic acid is changed as 5-chloro-8-（methoxycarbonylmethoxy）quinoline ligand（L） in complexes 1 and 2. Crystal data for 1： C12H10Br2 Cl Hg NO3, Mr = 612.07, triclinic, space group P1 with a = 8.5983（7）, b = 9.7726（6）, c = 10.1549（6） A, α = 66.355（6）, β = 77.067（8）, γ = 78.803（8）°, V = 756.6（9）A^3, Z = 2, Dc = 2.687 g/cm^3, F（000） = 560, μ = 15.633 mm^-1, R = 0.0351 and w R = 0.0504. Crystal data for 2： C24H20Cl4 Cu N2O6, Mr = 637.76, triclinic, space group P1 with a = 10.5324（9）, b = 11.2377（16）, c = 12.0143（12） ？, α = 83.413（11）, β = 64.475（9）, γ = 83.144（11）°, V = 1270.9（2） ？3, Z = 2, Dc = 1.667 g/cm3, F（000） = 646, μ = 1.324 mm-1, R = 0.0408 and wR = 0.0922. In 1, the HgII centre is a distorted trigonal planar geometry comprised of two Br atoms and one quinoline N atom of L. Intermolecular π-π, C–H…π stacking interactions and intermolecular C–H…Br hydrogen bonds are observed in the molecular packing of 1. In complex 2, each CuII center has a distorted octahedral geometry comprised of two chloride ions, two quinoline N atoms and two O atoms of two L ligands. Intermolecular C–H…Cl hydrogen bonds exist in the molecular packing of 2. The fluorescence emission peak of complexes 1 and 2 appears near 406 and 410 nm, respectively. Optical diffuse-reflection spectral results suggest complex 1 has the property of semiconductor.
