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
Objective The neuroprotective roles of cyclooxygenase （COX） and lipooxygenase （LOX） inhibitors have been well documented. Quinolinic acid （QA） is a well-known excitotoxic agent that could induce behavioral, morp...Objective The neuroprotective roles of cyclooxygenase （COX） and lipooxygenase （LOX） inhibitors have been well documented. Quinolinic acid （QA） is a well-known excitotoxic agent that could induce behavioral, morphological and biochemical alterations similar with symptoms of Huntington’s disease （HD）, by stimulating NMDA receptors. However, the exact roles of COX and LOX inhibitors in HD have not yet been explained. The present study aims to elucidate the effects of caffeic acid （a specific inhibitor for LOX）, rofecoxib （a specific inhibitor for COX-2）, and their combination in ameliorating QA-induced neurotoxicity in rats. Methods QA was injected into the right striatum of rats to induce neurotoxicity. Caffeic acid and rofecoxib were then orally administered separately. In the combination study, caffeic acid and rofecoxib were administered together. After that, a series of behavioral assessments were conducted to determine the effects of caffeic acid and rofecoxib, respectively, and the co-effect of caffeic acid and rofecoxib, against QA-induced neurotoxicity. Results Intrastriatal QA administration （300 nmol） not only induced a significant reduction in body weight and motor incoordination, but also altered the redox status （decreased glutathione and increased oxidized glutathione level） in striatum, as compared to the sham group. Moreover, chronic treatment with caffeic acid （5 mg/kg and 10 mg/kg, respectively, p.o.） or rofecoxib （10 mg/kg, p.o.） could significantly attenuate QA-induced behavioral alterations and restore the redox status in striatum. However, at the dose of 2.5 mg/kg, caffeic acid did not show any significant effects on these parameters in QA-treated rats. Furthermore, the combination of rofecoxib （10 mg/kg） and caffeic acid （5 mg/kg） could significantly protect against QA neurotoxicity. Conclusion The in vivo study indicates that excitotoxic injury to the brain might affect oxidant/antioxidant equilibrium by eliciting changes in glutathione. Moreover, the LOX and the COX pathways may be both involved in quinolinic-induced neurotoxicity, which provides a promising target for HD treatment.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
KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to eva...KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to evaluate the influence of varying hydrothermal synthesis temperatures on the physicochemical properties of both the KIT-5/Beta supports and the resulting catalysts.The catalytic performances of catalysts were evaluated under reaction conditions of 320℃,4 MPa H_(2)pressure,and a weight hourly space velocity(WHSV)of 4.8 h^(-1)for hydrodenitrogenation(HDN)of quinoline.The results indicated that the specific surface area and pore structure of the materials could be effectively regulated by adjusting the hydrothermal synthesis temperature,which in turn influenced the number of active sites on the catalyst.The NiW/KB-125 catalyst,synthesized at 125℃,presented the highest quinoline HDN efficiency(96.8%),which can be attributed to its favorable pore channel structure,greater Brønsted acid number,higher degree of metal sulfidation(80.12%)and appropriate metal-support interaction(MSI).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
Ischemic stroke(IS)is a prevalent neurological disorder often resulting in significant disability or mortality.Resveratrol,extracted from Polygonum cuspidatum Sieb.et Zucc.(commonly known as Japanese knotweed),has bee...Ischemic stroke(IS)is a prevalent neurological disorder often resulting in significant disability or mortality.Resveratrol,extracted from Polygonum cuspidatum Sieb.et Zucc.(commonly known as Japanese knotweed),has been recognized for its potent neuroprotective properties.However,the neuroprotective efficacy of its derivative,(E)-4-(3,5-dimethoxystyryl)quinoline(RV02),against ischemic stroke remains inadequately explored.This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo.The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions.The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species(ROS)through mitophagy activation.Furthermore,Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro.These results suggest that RV02 shows promise as a neuroprotective agent,with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.展开更多
The tricyclic pyrrolo[2,3-c]quinoline framework is the core structure of numerous natural products and bioactive molecules.Their syntheses usually rely on either forming middle pyridine ring by pyridannulation of 2-(1...The tricyclic pyrrolo[2,3-c]quinoline framework is the core structure of numerous natural products and bioactive molecules.Their syntheses usually rely on either forming middle pyridine ring by pyridannulation of 2-(1H-pyrrol-3-yl)anilines or building the pyrrole ring onto quinolines.We herein disclosed an unprecedented diheterocyclization-migration strategy for the de novo synthesis of 4-sulfonyl pyrrolo[2,3-c]quinolines from two distinct isocyanides.This methodology successively constructed the pyridine and pyrrole rings of this tricyclic scaffold in a single operation,along with remote migration of the sulfonyl group.Moreover,a collective total synthesis of alkaloids marinoquinoline A-C,H and K was accomplished by using the resulting 4-sulfonyl pyrrolo[2,3-c]quinoline as a common platform.展开更多
This study explores green and low-viscosity deep eutectic solvents(DESs) for the efficient extraction of quinoline(QUI) from wash oil.The hydrogen bond donors and acceptors constituting DESs were initially screened ba...This study explores green and low-viscosity deep eutectic solvents(DESs) for the efficient extraction of quinoline(QUI) from wash oil.The hydrogen bond donors and acceptors constituting DESs were initially screened based on thermodynamic properties predicted by the conductor-like screening model for real solvents(COSMO-RS),followed by further selection considering the viscosity and cost of the formed DESs.Phase equilibrium experiments showed that the DES composed of triethylmethylammonium chloride and formic acid exhibited the best extraction performance among the selected candidates.Key extraction parameters were optimized experimentally,achieving a maximum QUI extraction efficiency of 97.18% under mild conditions.Molecular dynamics simulations revealed that the interactions between quaternary ammonium cations and QUI play a crucial role in the extraction mechanism.This study provides insights into the use of DESs for QUI extraction and demonstrates their potential for application to other coal tar derivatives.展开更多
The development of highly efficient non-noble metal catalysts for the hydrogenation of N-heteroarenes under mild condition is of great importance for both theoretical and industrial applications,which can efficiently ...The development of highly efficient non-noble metal catalysts for the hydrogenation of N-heteroarenes under mild condition is of great importance for both theoretical and industrial applications,which can efficiently reduce energy consumption and environmental pollution.In this work,we found that the prepared CoCu nano-alloy catalyst after exposed in the air over 24 h(named Co_(1)Cu_(1)/C)exhibited a dramatically improved catalytic performance(yield from trace to>99%)for quinoline hydrogenation under mild reaction conditions(60℃,3 MPa H_(2)).According to the characterization,the catalyst Co_(1)Cu_(1)/C exhibited the strong interaction between Co and Cu.Meanwhile,it was endowed with a stable partial oxidation surface.The unsaturated oxygen coordinated surface of Co_(1)Cu_(1)/C presented a moderate binding for quinoline and 1,2,3,4-tetrahydroquinoline,which could efficiently avoid the deactivation of catalyst and favor the hydrogenation kinetics.The density functional theory(DFT)calculations coupled with X ray-based structural analyses suggested that the unsaturated oxygen coordinated surface could lower the diffusion energy of the active hydrogen species and the reaction barrier for quinoline hydrogenation which resulted from the d-p orbital electron coupling.This work revealed that the catalytic performance of nano-alloy catalysts might not only be ascribed to the interaction between metals,while the unsaturated oxygen coordination of metallic surfaces played an important role.展开更多
Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileg...Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.展开更多
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clin...Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer＇s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E （50, 100, 200 mg/kg）, and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.展开更多
Chronic induction of the kynurenine pathway（KP） contributes to neuroinflammation by producing the excitotoxin quinolinic acid（QUIN）. This has led to significant interest in the development of inhibitors of this pa...Chronic induction of the kynurenine pathway（KP） contributes to neuroinflammation by producing the excitotoxin quinolinic acid（QUIN）. This has led to significant interest in the development of inhibitors of this pathway, particularly in the context of neurodegenerative disease. However, acute spinal cord injury（SCI） also results in deleterious increases in QUIN, as secondary inflammatory processes mediated largely by infiltrating macrophages, become predominant. QUIN mediates significant neurotoxicity primarily by excitotoxic stimulation of the N-methyl-D-aspartate receptor, but other mechanisms of QUIN toxicity are known. More recent focus has assessed the contribution that neuroinflammation and modulations in the KP make in mood and psychiatric disorders with recent studies linking inflammation and modulations in the KP, to impaired cognitive performance and depressed mood in SCI patients. We hypothesize that these findings suggest that in SCI, inhibition of QUIN production and other metabolites, may have multiple therapeutic modalities and further studies investigating this are warranted. However, for central nervous system-based conditions, achieving good blood-brain-barrier permeability continues to be a limitation of current KP inhibitors.展开更多
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent ag...Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.展开更多
A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase （HMG CoA reductase） inhibitors.One member of this series,（4R,6S）-6-...A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase （HMG CoA reductase） inhibitors.One member of this series,（4R,6S）-6-{（E）-2-[6-fluoro-7-chloro-4-（4-fluorophenoxy-quinoline）-3-yl-]-ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one （3d）,showed more potent activity than rosuvastatin or pitavastatin to inhibit the rat HMG CoA reductase in vitro.This compound was selected for the extensive preclinical development as a potential hypocholesterolemic candidate.展开更多
The kynurenine pathway(KP)has been shown to be involved in the pathophysiology of dementia diseases.Among the dementia diseases,the neurodegenerative diseases Alzheimer's disease and cerebrovascular diseases are v...The kynurenine pathway(KP)has been shown to be involved in the pathophysiology of dementia diseases.Among the dementia diseases,the neurodegenerative diseases Alzheimer's disease and cerebrovascular diseases are vascular.The highest incidence of dementia.KP activation results in the production of neuroactive metabolites,which may interfere with normal neuronal function,leading to the appearance of symptoms of cognitive impairment.This review investigated KP's involvement in the neurological diseases Alzheimer's disease and vascular dementia,suggesting that KP is a potential therapeutic target for both diseases.展开更多
Objective To investigate the kinetics of quinoline biodegradation by Burkholderia pickttii, a Gram negative rod-shaped aerobe, isolated in our laboratory. Methods HPLC (Hewlett-Packard model 5050 with an UV detector) ...Objective To investigate the kinetics of quinoline biodegradation by Burkholderia pickttii, a Gram negative rod-shaped aerobe, isolated in our laboratory. Methods HPLC (Hewlett-Packard model 5050 with an UV detector) was used for the analysis of quinoline concentration. GC/MS method was used to identify the intermediate metabolites of quinoline degradation. Results The biodegradation of quinoline was inhibited by quinoline at a high concentration, and the degradation process could be described by the Haldane model. The kinetic parameters based on Haldane substrate inhibition were evaluated. The values were v = 0.44 h-1,Ks=166.7 mg/L, Ki= 650 mg/L, respectively. The quinoline concentration to avoid substrate inhibition was inferred theoretically and determined to be 329 mg/L. Conclusion The biodegradation of quinoline conforms to the Haldane inhibition model and the main intermediate metabolite of quinoline biodegradation is 2-hydroxy-quinoline.展开更多
The adsorption removal of indole and quinoline in octane with and without toluene over zeolites NaY and Yttrium Ion-exchanged Y(YY)using batch adsorption experiments was studied at 25℃and 0.1 MPa.YY was prepared by t...The adsorption removal of indole and quinoline in octane with and without toluene over zeolites NaY and Yttrium Ion-exchanged Y(YY)using batch adsorption experiments was studied at 25℃and 0.1 MPa.YY was prepared by treating NaY with Y(NO3)3 solution twice via liquid ion-exchange method.NaY and YY were both characterized by XRD,SEM,N2 adsorption,XRF,NH3-TPD,and pyridine-FTIR techniques.Adsorption isotherms of indole,quinoline and toluene in octane were conducted at 25.0℃to explain the influence of toluene on nitrogen removal over NaY and YY.The partial destruct of the crystalline structure of NaY was observed after the introduction of yttrium ion,which led to an evident decline in BET surface area and pore volume of YY.Strong Br?nsted acidity and medium Lewis acidity were introduced by yttrium ion-exchange.Though the specific surface area and pore volume of YY were much lower than those of NaY,YY exhibited equivalent adsorption capacities for indole and quinoline as NaY in model fuels without toluene.In the presence of 20 vol%toluene,however,YY exhibited much higher adsorption capacities for indole and quinoline than NaY,especially in the case of quinoline.The improved toluene-tolerant of YY was ascribed to the strong acid–base interaction between YY and quinoline and the decreased adsorption strength between YY and toluene.展开更多
Au Pd nanoalloys with tunable Pd concentrations have been synthesized and used as model catalysts. They have been directly imaged by high-angle annular dark-field scanning transmission electron microscopy and investig...Au Pd nanoalloys with tunable Pd concentrations have been synthesized and used as model catalysts. They have been directly imaged by high-angle annular dark-field scanning transmission electron microscopy and investigated by thorough analyses of their extended X-ray absorption fine structure, X-ray absorption near-edge structure, X-ray diffraction and X-ray photoelectron spectroscopy measurements. The bimetallic nanoparticles are embedded in a carbonaceous matrix and have almost an identical structure at the atomic level and the same electronic properties as Au Pd bulk alloys with the same compositions. The d-electron increase at surface Pd sites is determined by the Pd concentration of the alloy. Similarly, their activation entropy and catalytic activity for the hydrogenation of quinoline is related to the Pd concentration, with Au50 Pd50 the most active of the alloys investigated. An almost 11 times higher activity was achieved compared to a pure Pd catalyst. The experimentally measurable surface d charge at the Pd sites in the Au Pd was found to linearly correlate with the activation entropy and catalytic activity for the hydrogenation of quinoline. The alloy structure is stable, showing negligible metal segregation, dissolution-redeposition and aggregation during the hydrogenation process which involves strong adsorption.展开更多
An eco-friendly protocol for the synthesis of various 2-sulfonyl quinolines/pyridines through sulfonylation of heteroaromatic N-oxides with sodium sulfinates in water at ambient temperature under metal-and oxidant-fre...An eco-friendly protocol for the synthesis of various 2-sulfonyl quinolines/pyridines through sulfonylation of heteroaromatic N-oxides with sodium sulfinates in water at ambient temperature under metal-and oxidant-free conditions has been developed.The mild reaction conditions,high reaction efficiency,operational simplicity,short reaction time and remarkable functional-group compatibility make the developed protocol very attractive for the preparation of 2-sulfonyl N-heteroaromatic compounds.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support from University Grants Commission, New Delhi, for carrying out the present study
文摘Objective The neuroprotective roles of cyclooxygenase （COX） and lipooxygenase （LOX） inhibitors have been well documented. Quinolinic acid （QA） is a well-known excitotoxic agent that could induce behavioral, morphological and biochemical alterations similar with symptoms of Huntington’s disease （HD）, by stimulating NMDA receptors. However, the exact roles of COX and LOX inhibitors in HD have not yet been explained. The present study aims to elucidate the effects of caffeic acid （a specific inhibitor for LOX）, rofecoxib （a specific inhibitor for COX-2）, and their combination in ameliorating QA-induced neurotoxicity in rats. Methods QA was injected into the right striatum of rats to induce neurotoxicity. Caffeic acid and rofecoxib were then orally administered separately. In the combination study, caffeic acid and rofecoxib were administered together. After that, a series of behavioral assessments were conducted to determine the effects of caffeic acid and rofecoxib, respectively, and the co-effect of caffeic acid and rofecoxib, against QA-induced neurotoxicity. Results Intrastriatal QA administration （300 nmol） not only induced a significant reduction in body weight and motor incoordination, but also altered the redox status （decreased glutathione and increased oxidized glutathione level） in striatum, as compared to the sham group. Moreover, chronic treatment with caffeic acid （5 mg/kg and 10 mg/kg, respectively, p.o.） or rofecoxib （10 mg/kg, p.o.） could significantly attenuate QA-induced behavioral alterations and restore the redox status in striatum. However, at the dose of 2.5 mg/kg, caffeic acid did not show any significant effects on these parameters in QA-treated rats. Furthermore, the combination of rofecoxib （10 mg/kg） and caffeic acid （5 mg/kg） could significantly protect against QA neurotoxicity. Conclusion The in vivo study indicates that excitotoxic injury to the brain might affect oxidant/antioxidant equilibrium by eliciting changes in glutathione. Moreover, the LOX and the COX pathways may be both involved in quinolinic-induced neurotoxicity, which provides a promising target for HD treatment.
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 Autonomous Research Project of SKLCC(2024BWZ003)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA0390401)the Doctoral Research Start-up Funding of Shanxi Institute of Technology(026012).
文摘KIT-5/Beta composite supports were synthesized using an in situ self-assembly hydrothermal method,and NiW/KIT-5/Beta catalysts were prepared by impregnation.A series of characterization techniques were utilized to evaluate the influence of varying hydrothermal synthesis temperatures on the physicochemical properties of both the KIT-5/Beta supports and the resulting catalysts.The catalytic performances of catalysts were evaluated under reaction conditions of 320℃,4 MPa H_(2)pressure,and a weight hourly space velocity(WHSV)of 4.8 h^(-1)for hydrodenitrogenation(HDN)of quinoline.The results indicated that the specific surface area and pore structure of the materials could be effectively regulated by adjusting the hydrothermal synthesis temperature,which in turn influenced the number of active sites on the catalyst.The NiW/KB-125 catalyst,synthesized at 125℃,presented the highest quinoline HDN efficiency(96.8%),which can be attributed to its favorable pore channel structure,greater Brønsted acid number,higher degree of metal sulfidation(80.12%)and appropriate metal-support interaction(MSI).
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supported by the National Natural ScienceFoundation of China (No.82174076)the Construction Project of Liaoning Provincial Key Laboratory,China (No.2022JH13/10200026)+2 种基金the Fundamental Research Funds for the Central Universities (No.N2220002)the 111 Project (No.B16009)the Research Project of Educational Commission of Liaoning Province (No.LJ212410164003)。
文摘Ischemic stroke(IS)is a prevalent neurological disorder often resulting in significant disability or mortality.Resveratrol,extracted from Polygonum cuspidatum Sieb.et Zucc.(commonly known as Japanese knotweed),has been recognized for its potent neuroprotective properties.However,the neuroprotective efficacy of its derivative,(E)-4-(3,5-dimethoxystyryl)quinoline(RV02),against ischemic stroke remains inadequately explored.This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo.The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions.The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species(ROS)through mitophagy activation.Furthermore,Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro.These results suggest that RV02 shows promise as a neuroprotective agent,with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
基金Financial support from the National Natural Science Foundation of China(No.22171168)the Taishan Scholar Program of Shandong Provincethe Shandong Provincial Natural Science Foundation(No.ZR2024MB104).
文摘The tricyclic pyrrolo[2,3-c]quinoline framework is the core structure of numerous natural products and bioactive molecules.Their syntheses usually rely on either forming middle pyridine ring by pyridannulation of 2-(1H-pyrrol-3-yl)anilines or building the pyrrole ring onto quinolines.We herein disclosed an unprecedented diheterocyclization-migration strategy for the de novo synthesis of 4-sulfonyl pyrrolo[2,3-c]quinolines from two distinct isocyanides.This methodology successively constructed the pyridine and pyrrole rings of this tricyclic scaffold in a single operation,along with remote migration of the sulfonyl group.Moreover,a collective total synthesis of alkaloids marinoquinoline A-C,H and K was accomplished by using the resulting 4-sulfonyl pyrrolo[2,3-c]quinoline as a common platform.
基金financially supported by the Natural Science Foundation of Shanxi Province (20210302123167)National Key Research and Development Program (2022YFC3902505)。
文摘This study explores green and low-viscosity deep eutectic solvents(DESs) for the efficient extraction of quinoline(QUI) from wash oil.The hydrogen bond donors and acceptors constituting DESs were initially screened based on thermodynamic properties predicted by the conductor-like screening model for real solvents(COSMO-RS),followed by further selection considering the viscosity and cost of the formed DESs.Phase equilibrium experiments showed that the DES composed of triethylmethylammonium chloride and formic acid exhibited the best extraction performance among the selected candidates.Key extraction parameters were optimized experimentally,achieving a maximum QUI extraction efficiency of 97.18% under mild conditions.Molecular dynamics simulations revealed that the interactions between quaternary ammonium cations and QUI play a crucial role in the extraction mechanism.This study provides insights into the use of DESs for QUI extraction and demonstrates their potential for application to other coal tar derivatives.
基金supported by the National Natural Science Foundation of China(22408302,22478363)the Hunan Provincial Department of Education scientific research project(24B0165)+2 种基金the Hunan Provincial Natural Science Foundation of China(2022JJ40431)the Guangdong Basic and Applied Basic Research Foundation(2021A1515110789)The Key Scientific Research Projects of Colleges and Universities in Henan Province(25A530001)。
文摘The development of highly efficient non-noble metal catalysts for the hydrogenation of N-heteroarenes under mild condition is of great importance for both theoretical and industrial applications,which can efficiently reduce energy consumption and environmental pollution.In this work,we found that the prepared CoCu nano-alloy catalyst after exposed in the air over 24 h(named Co_(1)Cu_(1)/C)exhibited a dramatically improved catalytic performance(yield from trace to>99%)for quinoline hydrogenation under mild reaction conditions(60℃,3 MPa H_(2)).According to the characterization,the catalyst Co_(1)Cu_(1)/C exhibited the strong interaction between Co and Cu.Meanwhile,it was endowed with a stable partial oxidation surface.The unsaturated oxygen coordinated surface of Co_(1)Cu_(1)/C presented a moderate binding for quinoline and 1,2,3,4-tetrahydroquinoline,which could efficiently avoid the deactivation of catalyst and favor the hydrogenation kinetics.The density functional theory(DFT)calculations coupled with X ray-based structural analyses suggested that the unsaturated oxygen coordinated surface could lower the diffusion energy of the active hydrogen species and the reaction barrier for quinoline hydrogenation which resulted from the d-p orbital electron coupling.This work revealed that the catalytic performance of nano-alloy catalysts might not only be ascribed to the interaction between metals,while the unsaturated oxygen coordination of metallic surfaces played an important role.
文摘Skeletal editing has emerged as a powerful tool in organic chemistry,enabling the simplification of synthetic routes to complex molecules[1].Indoles,electron-rich nitrogen-containing building blocks,represent privileged scaffolds prevalent in pharmaceuticals,natural products,and bioactive compounds.The application of skeletal editing strategies to modify such structures is highly valuable and in growing demand.Leveraging the electronrich nature of indoles at C2 and C3,single-carbon atom insertion using cationic carbyne equivalents offers an efficient approach for indole ring expansion to quinoline(Scheme 1a).However,existing methods predominantly rely on halocarbene precursors,which restricts the functional groups of ring-expanded products to halogen[2],alkyl,aryl,heteroaryl and ester moieties[3].This limitation hinders their utility in late-stage skeletal modifications of complex targets.
基金supported by the Foundation from Department of Education of Hubei Province,No.D20111903
文摘Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer＇s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E （50, 100, 200 mg/kg）, and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.
文摘Chronic induction of the kynurenine pathway（KP） contributes to neuroinflammation by producing the excitotoxin quinolinic acid（QUIN）. This has led to significant interest in the development of inhibitors of this pathway, particularly in the context of neurodegenerative disease. However, acute spinal cord injury（SCI） also results in deleterious increases in QUIN, as secondary inflammatory processes mediated largely by infiltrating macrophages, become predominant. QUIN mediates significant neurotoxicity primarily by excitotoxic stimulation of the N-methyl-D-aspartate receptor, but other mechanisms of QUIN toxicity are known. More recent focus has assessed the contribution that neuroinflammation and modulations in the KP make in mood and psychiatric disorders with recent studies linking inflammation and modulations in the KP, to impaired cognitive performance and depressed mood in SCI patients. We hypothesize that these findings suggest that in SCI, inhibition of QUIN production and other metabolites, may have multiple therapeutic modalities and further studies investigating this are warranted. However, for central nervous system-based conditions, achieving good blood-brain-barrier permeability continues to be a limitation of current KP inhibitors.
基金supported by the Région Centre-Val de Loire(2014 00094049–AP 2014-850)the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement n°278850(INMiND)
文摘Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.
基金The State New Drug Innovation (Grant No. 2009ZX09301-007)Shanghai Rising-Star Program (Grant No. 08QB1403800)Shanghai Innovation Action Project (Grant No. 09431901300)
文摘A series of 4-phenoxy quinoline-based mevalonolactone derivatives have been synthesized and evaluated as 3-hydroxy-3-methylglutaryl CoA reductase （HMG CoA reductase） inhibitors.One member of this series,（4R,6S）-6-{（E）-2-[6-fluoro-7-chloro-4-（4-fluorophenoxy-quinoline）-3-yl-]-ethenyl}-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one （3d）,showed more potent activity than rosuvastatin or pitavastatin to inhibit the rat HMG CoA reductase in vitro.This compound was selected for the extensive preclinical development as a potential hypocholesterolemic candidate.
基金Key R&D Projects of Shanxi Province(NO.201803D31129)Science and Technology Activities for Returned Students from Shanxi Province(No.[2018]123)
文摘The kynurenine pathway(KP)has been shown to be involved in the pathophysiology of dementia diseases.Among the dementia diseases,the neurodegenerative diseases Alzheimer's disease and cerebrovascular diseases are vascular.The highest incidence of dementia.KP activation results in the production of neuroactive metabolites,which may interfere with normal neuronal function,leading to the appearance of symptoms of cognitive impairment.This review investigated KP's involvement in the neurological diseases Alzheimer's disease and vascular dementia,suggesting that KP is a potential therapeutic target for both diseases.
基金The work was supported by the National Natural Science Foundation of China (Grant No. 29637010 50325824).
文摘Objective To investigate the kinetics of quinoline biodegradation by Burkholderia pickttii, a Gram negative rod-shaped aerobe, isolated in our laboratory. Methods HPLC (Hewlett-Packard model 5050 with an UV detector) was used for the analysis of quinoline concentration. GC/MS method was used to identify the intermediate metabolites of quinoline degradation. Results The biodegradation of quinoline was inhibited by quinoline at a high concentration, and the degradation process could be described by the Haldane model. The kinetic parameters based on Haldane substrate inhibition were evaluated. The values were v = 0.44 h-1,Ks=166.7 mg/L, Ki= 650 mg/L, respectively. The quinoline concentration to avoid substrate inhibition was inferred theoretically and determined to be 329 mg/L. Conclusion The biodegradation of quinoline conforms to the Haldane inhibition model and the main intermediate metabolite of quinoline biodegradation is 2-hydroxy-quinoline.
基金the financial support from Natural Science Foundation of China-Liaoning United Funds(U1508205)Fundamental Research Funds for the Central Universities(DUT15ZD113)the Key Laboratory of Applied Surface and Colloid Chemistry(Shanxi Normal University).
文摘The adsorption removal of indole and quinoline in octane with and without toluene over zeolites NaY and Yttrium Ion-exchanged Y(YY)using batch adsorption experiments was studied at 25℃and 0.1 MPa.YY was prepared by treating NaY with Y(NO3)3 solution twice via liquid ion-exchange method.NaY and YY were both characterized by XRD,SEM,N2 adsorption,XRF,NH3-TPD,and pyridine-FTIR techniques.Adsorption isotherms of indole,quinoline and toluene in octane were conducted at 25.0℃to explain the influence of toluene on nitrogen removal over NaY and YY.The partial destruct of the crystalline structure of NaY was observed after the introduction of yttrium ion,which led to an evident decline in BET surface area and pore volume of YY.Strong Br?nsted acidity and medium Lewis acidity were introduced by yttrium ion-exchange.Though the specific surface area and pore volume of YY were much lower than those of NaY,YY exhibited equivalent adsorption capacities for indole and quinoline as NaY in model fuels without toluene.In the presence of 20 vol%toluene,however,YY exhibited much higher adsorption capacities for indole and quinoline than NaY,especially in the case of quinoline.The improved toluene-tolerant of YY was ascribed to the strong acid–base interaction between YY and quinoline and the decreased adsorption strength between YY and toluene.
文摘Au Pd nanoalloys with tunable Pd concentrations have been synthesized and used as model catalysts. They have been directly imaged by high-angle annular dark-field scanning transmission electron microscopy and investigated by thorough analyses of their extended X-ray absorption fine structure, X-ray absorption near-edge structure, X-ray diffraction and X-ray photoelectron spectroscopy measurements. The bimetallic nanoparticles are embedded in a carbonaceous matrix and have almost an identical structure at the atomic level and the same electronic properties as Au Pd bulk alloys with the same compositions. The d-electron increase at surface Pd sites is determined by the Pd concentration of the alloy. Similarly, their activation entropy and catalytic activity for the hydrogenation of quinoline is related to the Pd concentration, with Au50 Pd50 the most active of the alloys investigated. An almost 11 times higher activity was achieved compared to a pure Pd catalyst. The experimentally measurable surface d charge at the Pd sites in the Au Pd was found to linearly correlate with the activation entropy and catalytic activity for the hydrogenation of quinoline. The alloy structure is stable, showing negligible metal segregation, dissolution-redeposition and aggregation during the hydrogenation process which involves strong adsorption.
基金financial support from the Hunan Provincial Natural Science Foundation of China (No.2019JJ20008)
文摘An eco-friendly protocol for the synthesis of various 2-sulfonyl quinolines/pyridines through sulfonylation of heteroaromatic N-oxides with sodium sulfinates in water at ambient temperature under metal-and oxidant-free conditions has been developed.The mild reaction conditions,high reaction efficiency,operational simplicity,short reaction time and remarkable functional-group compatibility make the developed protocol very attractive for the preparation of 2-sulfonyl N-heteroaromatic compounds.
