1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson＇s like symptoms in rodents.Quercetin（QC）i...1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson＇s like symptoms in rodents.Quercetin（QC）is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability.Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants（e.g.,Quercetin）.Therefore,the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats.MPTP（100μg/μL/rat,bilaterally）was injected intranigrally on days 1,4 and 7 using a digital stereotaxic apparatus.QC（25 and 50 mg/kg,intragastrically）and QC（25 mg/kg,intragastrically）in combination with piperine（2.5 mg/kg,intragastrically）were administered daily for 14 days starting from day 8 after the 3^（rd） injection of MPTP.On day 22,animals were sacrificed and the striatum was isolated for oxidative stress parameter（thiobarbituric acid reactive substances,nitrite and glutathione）,neuroinflammatory cytokine（interleukin-1β,interleukin-6,and tumor necrosis factor-α）and neurotransmitter（dopamine,norepinephrine,serotonin,gamma-aminobutyric acid,glutamate,3,4-dihydroxyphenylacetic acid,homovanillic acid,and 5-hydroxyindoleacetic acid）evaluations.Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance.Both QC（25 and 50 mg/kg）and QC（25 mg/kg）in combination with piperine（2.5 mg/kg）,in particular the combination therapy,significantly improved MPTP-induced behavioral abnormalities in rats,reversed the abnormal alterations of neurotransmitters in the striatum,and alleviated oxidative stress and inflammatory response in the striatum.These findings indicate that piperine can enhance the antioxidant and anti-inflammatory properties of QC,and QC in combination with piperine exhibits strong neuroprotective effects against MPTP-induced neurotoxicity.展开更多
Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also...Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also play a key role in the pathophysiology of various brain-related disorders. The present study was aimed to explore the protective effect of cyclooxygenase inhibitors on stress by using an animal model of chronic stress. Methods The animals were forced to swim individually for a period of 6 min every day for 15 d. Then, the behavior （locomotor activity, anxiety and memory） and biochemical （lipid peroxidation, nitrite level, reduced glutathione, and catalase） alterations were assessed. Results Forced swimming for 15 d caused impaired locomotor activity, anxiety-like behavior and decreased percentage of memory retention, as compared to na？ve mice （without chronic fatigue treatment）. Biochemical analysis revealed significant increases in lipid peroxidation and nitrite level, while levels of reduced glutathione and catalase activity were both decreased. Chronic treatment with naproxen （14 mg/kg, i.p.）, rofecoxib （5 mg/kg, i.p.）, meloxicam （5 mg/kg, i.p.）, nimesulide （5 mg/kg, i.p.） and valdecoxib （10 mg/kg, i.p.） significantly attenuated these behavioral and biochemical （oxidative damage） alterations in chronic-stressed mice. Conclusion The cyclooxygenase inhibitors could be used in the management of chronic fatigue-like conditions.展开更多
Evolution of computational modeling and simulation has given more emphasis on the research activities related to carbon nanotube(CNT)reinforced polymer composites recently.This paper presents the composite cylinder as...Evolution of computational modeling and simulation has given more emphasis on the research activities related to carbon nanotube(CNT)reinforced polymer composites recently.This paper presents the composite cylinder assemblage(CCA)approach based on continuum mechanics for investigating the elastic properties of a polymer resin reinforced by multi-walled carbon nanotubes(MWCNTs).A three-phase cylindrical representative volume element(RVE)model is employed based on CCA technique to elucidate the effects of inter layers,chirality,interspacing,volume fraction of MWCNT,interphase properties and temperature conditions on the elastic modulus of the composite.The interface region between CNT and polymer matrix is modeled as the third phase with varying material properties.The constitutive relations for each material system have been derived based on solid mechanics and proper interfacial traction continuity conditions are imposed.The predicted results from the CCA approach are in well agreement with RVE-based finite element model.The outcomes reveal that temperature softening effect becomes more pronounced at higher volume fractions of CNTs.展开更多
An account of 20 species under 11 genera of the family Fabaceae is presented based upon a thorough study of the collected specimens and field surveys in this paper from Sechu Tuan Nalla Wildlife Sanctuary,Chamba distr...An account of 20 species under 11 genera of the family Fabaceae is presented based upon a thorough study of the collected specimens and field surveys in this paper from Sechu Tuan Nalla Wildlife Sanctuary,Chamba district,Himachal Pradesh.Of these,five taxa are reported first time from the Chamba district of the state.The updated nomenclature of the species,local name if any,a brief description of the plant,flowering and fruiting period,distribution in the study area,habitat and ecology and specimen examined have been provided.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
基金Science and Engineering Board(SERB),Department of Science and Technology,Government of India,New Delhi for providing financial assistance under Fast Track Scheme(DST-SERB-FTYS)(SB/FT/LS-139/2012) to Dr.PK
文摘1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）is a neurotoxin that selectively damages dopaminergic neurons in the substantia nigra pars compacta and induces Parkinson＇s like symptoms in rodents.Quercetin（QC）is a natural polyphenolic bioflavonoid with potent antioxidant and anti-inflammatory properties but lacks of clinical attraction due to low oral bioavailability.Piperine is a well established bioavailability enhancer used pre-clinically to improve the bioavailability of antioxidants（e.g.,Quercetin）.Therefore,the present study was designed to evaluate the neuroprotective potential of QC together with piperine against MPTP-induced neurotoxicity in rats.MPTP（100μg/μL/rat,bilaterally）was injected intranigrally on days 1,4 and 7 using a digital stereotaxic apparatus.QC（25 and 50 mg/kg,intragastrically）and QC（25 mg/kg,intragastrically）in combination with piperine（2.5 mg/kg,intragastrically）were administered daily for 14 days starting from day 8 after the 3^（rd） injection of MPTP.On day 22,animals were sacrificed and the striatum was isolated for oxidative stress parameter（thiobarbituric acid reactive substances,nitrite and glutathione）,neuroinflammatory cytokine（interleukin-1β,interleukin-6,and tumor necrosis factor-α）and neurotransmitter（dopamine,norepinephrine,serotonin,gamma-aminobutyric acid,glutamate,3,4-dihydroxyphenylacetic acid,homovanillic acid,and 5-hydroxyindoleacetic acid）evaluations.Bilateral infusion of MPTP into substantia nigra pars compacta led to significant motor deficits as evidenced by impairments in locomotor activity and rotarod performance in open field test and grip strength and narrow beam walk performance.Both QC（25 and 50 mg/kg）and QC（25 mg/kg）in combination with piperine（2.5 mg/kg）,in particular the combination therapy,significantly improved MPTP-induced behavioral abnormalities in rats,reversed the abnormal alterations of neurotransmitters in the striatum,and alleviated oxidative stress and inflammatory response in the striatum.These findings indicate that piperine can enhance the antioxidant and anti-inflammatory properties of QC,and QC in combination with piperine exhibits strong neuroprotective effects against MPTP-induced neurotoxicity.
文摘Objective Cyclooxygenase isoenzyme is known to be expressed in different regions of brain, and is mainly used for the treatment of pain and inflammation. Recently, it is proposed that cyclooxygenase isoenzyme may also play a key role in the pathophysiology of various brain-related disorders. The present study was aimed to explore the protective effect of cyclooxygenase inhibitors on stress by using an animal model of chronic stress. Methods The animals were forced to swim individually for a period of 6 min every day for 15 d. Then, the behavior （locomotor activity, anxiety and memory） and biochemical （lipid peroxidation, nitrite level, reduced glutathione, and catalase） alterations were assessed. Results Forced swimming for 15 d caused impaired locomotor activity, anxiety-like behavior and decreased percentage of memory retention, as compared to na？ve mice （without chronic fatigue treatment）. Biochemical analysis revealed significant increases in lipid peroxidation and nitrite level, while levels of reduced glutathione and catalase activity were both decreased. Chronic treatment with naproxen （14 mg/kg, i.p.）, rofecoxib （5 mg/kg, i.p.）, meloxicam （5 mg/kg, i.p.）, nimesulide （5 mg/kg, i.p.） and valdecoxib （10 mg/kg, i.p.） significantly attenuated these behavioral and biochemical （oxidative damage） alterations in chronic-stressed mice. Conclusion The cyclooxygenase inhibitors could be used in the management of chronic fatigue-like conditions.
文摘Evolution of computational modeling and simulation has given more emphasis on the research activities related to carbon nanotube(CNT)reinforced polymer composites recently.This paper presents the composite cylinder assemblage(CCA)approach based on continuum mechanics for investigating the elastic properties of a polymer resin reinforced by multi-walled carbon nanotubes(MWCNTs).A three-phase cylindrical representative volume element(RVE)model is employed based on CCA technique to elucidate the effects of inter layers,chirality,interspacing,volume fraction of MWCNT,interphase properties and temperature conditions on the elastic modulus of the composite.The interface region between CNT and polymer matrix is modeled as the third phase with varying material properties.The constitutive relations for each material system have been derived based on solid mechanics and proper interfacial traction continuity conditions are imposed.The predicted results from the CCA approach are in well agreement with RVE-based finite element model.The outcomes reveal that temperature softening effect becomes more pronounced at higher volume fractions of CNTs.
文摘An account of 20 species under 11 genera of the family Fabaceae is presented based upon a thorough study of the collected specimens and field surveys in this paper from Sechu Tuan Nalla Wildlife Sanctuary,Chamba district,Himachal Pradesh.Of these,five taxa are reported first time from the Chamba district of the state.The updated nomenclature of the species,local name if any,a brief description of the plant,flowering and fruiting period,distribution in the study area,habitat and ecology and specimen examined have been provided.
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.
