A rapid, sensitive and accurate liquid chroma-tographic tandem mass spectrometric method is described for the determination of Mimosine in Mimosa pudica Linn. whole plant powder. Mi-mosine was extracted from the plant...A rapid, sensitive and accurate liquid chroma-tographic tandem mass spectrometric method is described for the determination of Mimosine in Mimosa pudica Linn. whole plant powder. Mi-mosine was extracted from the plant using 1.0% HCl in water. The chromatographic separation was achieved using a Thermo Hypurity C18 (50 x 4.6 mm) 5.0 μ column interfaced with a triple quadrapole mass spectrometer. The mobile phase consisted of a mixture of Methanol: 10 mM ammonium formate buffer whose pH was ad-justed to 3.00 ± 0.05 with formic acid (80:20, v/v) and was delivered at a flow rate of 1.0 mL min-1. Electrospray ionization (ESI) source operated in the negative ion mode was used for the quantitation. Detection was performed using an Applied Biosystems Sciex API 3200 Mass spec-trometer. The method was found to be simple, precise, accurate, fast, specific and sensitive and can be used for routine quality control analysis of Mimosine in Mimosa pudica Linn.展开更多
Evidence suggests that increased level/aggregation of beta-amyloid(Aβ)peptides initiate neurodegeneration and subsequent development of Alzheimer’s disease(AD).At present,there is no effective treatment for AD.In th...Evidence suggests that increased level/aggregation of beta-amyloid(Aβ)peptides initiate neurodegeneration and subsequent development of Alzheimer’s disease(AD).At present,there is no effective treatment for AD.In this study,we reported the effects of gold nanoparticles surface-functionalized with a plant-based amino acid mimosine(Mimo-AuNPs),which is found to cross the blood-brain barrier,on the Aβfibrillization process and toxicity.Thioflavin T kinetic assays,fluorescence imaging and electron microscopy data showed that Mimo-AuNPs were able to suppress the spontaneous and seed-induced A_(1-42) aggregation.Spectroscopic studies,molecular docking and biochemical analyses further revealed that Mimo-AuNPs stabilize A_(1-42) to remain in its monomeric state by interacting with the hydrophobic domain of A_(1-42)(i.e.,Lys16 to Ala21)there by preventing a conformational shift towards theβ-sheet structure.Additionally,Mimo-AuNPs were found to trigger the disassembly of matured A_(1-42) fibers and increased neuronal viability by reducing phosphorylation of tau protein and the production of oxyradicals.Collectively,these results reveal that the surface-functionalization of gold nanoparticles with mimosine can attenuate Aβfibrillization and neuronal toxicity.Thus,we propose Mimo-AuNPs may be used as a potential treatment strategy towards AD-related pathologies.展开更多
Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown ...Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown that mimosine can also inhibit the replication of Xenopus ribo-some DNA (rDNA) plasmid reversibly. The high structure similarity between mimosine展开更多
Objective:To evaluate whether hypoxia inducible factor(HIF-1α) targeting pharmacological drugs,echinomycin,resveratrol and CdCl_2 which inhibit HIF-1α stimulation,and mimosine,which enhances the stability of HIF-1α...Objective:To evaluate whether hypoxia inducible factor(HIF-1α) targeting pharmacological drugs,echinomycin,resveratrol and CdCl_2 which inhibit HIF-1α stimulation,and mimosine,which enhances the stability of HIF-1α present antileishmanial properties.Methods:The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis.Results:Resveratrol and CdCl_2 reduced the parasite load [IC50,(27.3±2.25) μM and(24.8±0.95) μM,respectively].The IC50 value of echinomycin was(22.7±7.36) nM and mimosine did not alter the parasite load in primary macrophages.The macrophage viability IC50 values for resveratrol,echinomycin and CdCl_2 and mimosine were >40 μM,>100 nM,> 200 μM and>2 000 μM,respectively.In vivo no differences between cutaneous lesions from control,resveratrol-and echinomycin-treated Balb/c mice were detected.Conclusions:Resveratrol,echinomycin and CdCl_2 reduce parasite survival in vitro.The HIF-1α targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies.展开更多
文摘A rapid, sensitive and accurate liquid chroma-tographic tandem mass spectrometric method is described for the determination of Mimosine in Mimosa pudica Linn. whole plant powder. Mi-mosine was extracted from the plant using 1.0% HCl in water. The chromatographic separation was achieved using a Thermo Hypurity C18 (50 x 4.6 mm) 5.0 μ column interfaced with a triple quadrapole mass spectrometer. The mobile phase consisted of a mixture of Methanol: 10 mM ammonium formate buffer whose pH was ad-justed to 3.00 ± 0.05 with formic acid (80:20, v/v) and was delivered at a flow rate of 1.0 mL min-1. Electrospray ionization (ESI) source operated in the negative ion mode was used for the quantitation. Detection was performed using an Applied Biosystems Sciex API 3200 Mass spec-trometer. The method was found to be simple, precise, accurate, fast, specific and sensitive and can be used for routine quality control analysis of Mimosine in Mimosa pudica Linn.
基金This work was supported by grants from APRI-ASANT and CIHR(MOP-84480)SK and from APRI(APRI 201600028)HW.SynAD,University of Alberta provided a part of the postdoctoral fellowships for BGA,QW and KG.
文摘Evidence suggests that increased level/aggregation of beta-amyloid(Aβ)peptides initiate neurodegeneration and subsequent development of Alzheimer’s disease(AD).At present,there is no effective treatment for AD.In this study,we reported the effects of gold nanoparticles surface-functionalized with a plant-based amino acid mimosine(Mimo-AuNPs),which is found to cross the blood-brain barrier,on the Aβfibrillization process and toxicity.Thioflavin T kinetic assays,fluorescence imaging and electron microscopy data showed that Mimo-AuNPs were able to suppress the spontaneous and seed-induced A_(1-42) aggregation.Spectroscopic studies,molecular docking and biochemical analyses further revealed that Mimo-AuNPs stabilize A_(1-42) to remain in its monomeric state by interacting with the hydrophobic domain of A_(1-42)(i.e.,Lys16 to Ala21)there by preventing a conformational shift towards theβ-sheet structure.Additionally,Mimo-AuNPs were found to trigger the disassembly of matured A_(1-42) fibers and increased neuronal viability by reducing phosphorylation of tau protein and the production of oxyradicals.Collectively,these results reveal that the surface-functionalization of gold nanoparticles with mimosine can attenuate Aβfibrillization and neuronal toxicity.Thus,we propose Mimo-AuNPs may be used as a potential treatment strategy towards AD-related pathologies.
文摘Mimosine, a plant amino acid, is a reversible cell cycle inhibitor. Biochemical studies have indicated that mimosine may act at multiple levels near the Gl/S interface. By using mi-croinjection technique, it is shown that mimosine can also inhibit the replication of Xenopus ribo-some DNA (rDNA) plasmid reversibly. The high structure similarity between mimosine
基金supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo,Conselho Nacional de Desenvolvimento Científico e Tecnologico (NO.2009/10771-9)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior (NO.301052/2009-3),Brazil
文摘Objective:To evaluate whether hypoxia inducible factor(HIF-1α) targeting pharmacological drugs,echinomycin,resveratrol and CdCl_2 which inhibit HIF-1α stimulation,and mimosine,which enhances the stability of HIF-1α present antileishmanial properties.Methods:The leishmanicidal effect of drugs was evaluated in mouse macrophages and Balb/c mouse model for cutaneous leishmaniosis.Results:Resveratrol and CdCl_2 reduced the parasite load [IC50,(27.3±2.25) μM and(24.8±0.95) μM,respectively].The IC50 value of echinomycin was(22.7±7.36) nM and mimosine did not alter the parasite load in primary macrophages.The macrophage viability IC50 values for resveratrol,echinomycin and CdCl_2 and mimosine were >40 μM,>100 nM,> 200 μM and>2 000 μM,respectively.In vivo no differences between cutaneous lesions from control,resveratrol-and echinomycin-treated Balb/c mice were detected.Conclusions:Resveratrol,echinomycin and CdCl_2 reduce parasite survival in vitro.The HIF-1α targeting pharmacological drugs require further study to more fully determine their anti-Leishmania potential and their role in therapeutic strategies.
