Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its developmen...Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its development and progression.Indeed,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease models.The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in mice.LCN were prepared by the nanoprecipitation method.Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice.In the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in mice.However,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test.Moreover,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 downregulation.Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 modulation.This study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(approval No.02-2015)on April 16,2015.展开更多
Malaria is a parasitic disease which has as etiological agents protozoa of the genus Plasmodium prevalent in tropical countries. The appearance of Plasmodium strains resistant to artemisinin has become necessary the d...Malaria is a parasitic disease which has as etiological agents protozoa of the genus Plasmodium prevalent in tropical countries. The appearance of Plasmodium strains resistant to artemisinin has become necessary the development of new drugs using computational tools to combat this epidemic. Diverse transporter proteins can act as antimalarials targets, thereby being the enzyme deoxyhypusine synthase a promising antimalarial target. The present study aimed to investigate 15 most active inhibitors of deoxyhypusine synthase target, deposited in databases Binding DB, in order to trace a pattern of physicochemical, pharmacokinetic and toxicological properties of the inhibitors for this enzyme and propose new inhibitors of deoxyhypusine synthase target. The physicochemical properties were obtained according to the Lipinski parameters to evaluate oral absorption. Based on the certain properties were proposed three new inhibitors (A, B and C). The ADME/Tox properties were calculated for new inhibitors compared with results of the selected compounds. The fifteen inhibitors for oral administration showed satisfactory results, because they have adapted to the Lipinski parameters. In relation to the penetration of the blood-brain barrier the inhibitors analyzed showed penetration values less than 1, and ranged from 0.0411815 to 0.481764, being that the compound 1 showed value of CBrain/CBlood = 0.135467. Compound B showed a higher strength in plasma protein binding in relation to the compound 1, having a variation be-tween them of ±1.489344. Therefore, the compound B would present a longer halflife compared with compound 1. The proposed compounds showed positive and satisfactory results, being able to reach less adverse effects related to the central nervous system depending of administered dose.展开更多
AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcin...AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcinoma （HepG2） cells were treated with spray-dried extracts of Phyllanthus niruri （SDEPN） either alone or in combination with cisplatin at differ- ent concentrations （0.5 mg/mL and 1 mg/mL） for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni＇s test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS： SDEPN had significantly different cyto- toxic effects on HT29 （2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05） and HepG2 （5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001） cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 （1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05） and HepG2 （14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001） cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells （HepG2 cells for 4 h： 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h： 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h： 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h： 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001）. In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed （12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001）. HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin （12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001）. CONCLUSION： SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.展开更多
Flaxseed (Linum usitatissimum L.) is composed mainly of bioactive components such as polyphenols, polyunsaturated fatty acids, fiber and lignans. Flaxseed can be found in different presentation forms (grain or flour) ...Flaxseed (Linum usitatissimum L.) is composed mainly of bioactive components such as polyphenols, polyunsaturated fatty acids, fiber and lignans. Flaxseed can be found in different presentation forms (grain or flour) and varieties (brown or golden);however, questions have arisen as to whether the presentation form and/or variety may influence the health effects. The objective of this study was to evaluate the effects on blood pressure, anthropometric and oxidative parameters in healthy human volunteers. All subjects received 40 gram aliquots of flaxseed and were instructed to consume them in their entirety mixed with water in the morning for a period of 14 days. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins via dietary intervention with golden flaxseed grains. There were no significant differences in anthropometric parameters, blood pressure, DNA damage and micronuclei frequency after 14-day supplementation. This research indicates that golden flaxseed grains can be a valuable adjunct for disease prevention and protecting the organism against oxidative damage.展开更多
基金This study was supported by the Rio Grande do Sul Science Foundation(FAPERGS),grants#16/2551-0000207-0 and 16/0526-5(PRONUPEQ)(to SP)National Counsel of Technological and Scientific Development(CNPq)(Universal grants#423435/2016-7 and 460122/2014-2)and for student scholarships(to CL,SEH and DSÁ).
文摘Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its development and progression.Indeed,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease models.The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in mice.LCN were prepared by the nanoprecipitation method.Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice.In the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in mice.However,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test.Moreover,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 downregulation.Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 modulation.This study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(approval No.02-2015)on April 16,2015.
基金We gratefully acknowledge the support provided by the Brazilian Agency National Council of Scientific and Technological Development(CNPq-Brazil)；The authors would like to thank the Scientific Initiation Program(IC/CNPq/UNIFAP)；and the Laboratory of Modeling and Computational Chemistry of Federal University of Amapáfor computational support.
文摘Malaria is a parasitic disease which has as etiological agents protozoa of the genus Plasmodium prevalent in tropical countries. The appearance of Plasmodium strains resistant to artemisinin has become necessary the development of new drugs using computational tools to combat this epidemic. Diverse transporter proteins can act as antimalarials targets, thereby being the enzyme deoxyhypusine synthase a promising antimalarial target. The present study aimed to investigate 15 most active inhibitors of deoxyhypusine synthase target, deposited in databases Binding DB, in order to trace a pattern of physicochemical, pharmacokinetic and toxicological properties of the inhibitors for this enzyme and propose new inhibitors of deoxyhypusine synthase target. The physicochemical properties were obtained according to the Lipinski parameters to evaluate oral absorption. Based on the certain properties were proposed three new inhibitors (A, B and C). The ADME/Tox properties were calculated for new inhibitors compared with results of the selected compounds. The fifteen inhibitors for oral administration showed satisfactory results, because they have adapted to the Lipinski parameters. In relation to the penetration of the blood-brain barrier the inhibitors analyzed showed penetration values less than 1, and ranged from 0.0411815 to 0.481764, being that the compound 1 showed value of CBrain/CBlood = 0.135467. Compound B showed a higher strength in plasma protein binding in relation to the compound 1, having a variation be-tween them of ±1.489344. Therefore, the compound B would present a longer halflife compared with compound 1. The proposed compounds showed positive and satisfactory results, being able to reach less adverse effects related to the central nervous system depending of administered dose.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq (470179/2009-0) for financial support and Postgraduate Program in Pharmaceutical Sciences,Federal University of Rio Grande do Norte
文摘AIM：To investigate the cytotoxic effects of spray-dried extracts of Phyllanthus niruri in combination with cis- platin on two cancer cell lines. METHODS： Colorectal carcinoma （HT29） and human hepatocellular carcinoma （HepG2） cells were treated with spray-dried extracts of Phyllanthus niruri （SDEPN） either alone or in combination with cisplatin at differ- ent concentrations （0.5 mg/mL and 1 mg/mL） for 4 h and 24 h. To verify and quantify cancer cells treated with these products as well as identify the cell cycle stage and cell viability, we stained the cells with prop- idium iodide and assessed them by flow cytometry. The percentage of cells in different cell cycle phases was quantified and data were expressed as histo- grams. Significant differences between groups were determined using analysis of variance and Bonferroni＇s test, as indicated. A value of P 〈 0.05 was considered to be statistically significant. RESULTS： SDEPN had significantly different cyto- toxic effects on HT29 （2.81 4- 0.11 vs 3.51 4- 1.13, P 〉 0.05） and HepG2 （5.07± 0.3 vs 15.9 ± 1.04, P 〈 0.001） cells when compared to control cells for 4 h. SDEPN also had significantly different cytotoxic effects on HT29 （1.91 ± 0.57 vs 4.53± 1.22, P 〉 0.05） and HepG2 （14.56 ± 1.6 vs 35.67 ± 3.94, P 〈 0.001） cells when compared to control cells for 24 h. Both cell lines were killed by cisplatin in a dose-dependent manner compared to control cells （HepG2 cells for 4 h： 10.78 ± 1.58 vs 53.89 ± 1.53, P 〈 0.001; 24 h： 8.9 ± 1.43 vs 62.78 ± 1.87, P 〈 0.001 and HT29 cells for 4 h： 9.52 ±0.913 vs 49.86 ± 2.89, P 〈 0.001; 24 h： 11.78 ± 1.05 vs 53.34 ± 2.65, P 〈 0.001）. In HT29 cells, pretreat- ment with SDEPN and subsequent treatment with cis-platin resulted in a greater number of cells being killed （12.78 ± 1.01 vs 93.76 ± 1.6, P 〈 0.001）. HepG2 cells showed significant cell killing with treatment with SDEPN when combined with cisplatin （12.87 ± 2.78 vs 78.8 ± 3.02, P 〈 0.001）. CONCLUSION： SDEPN is selectively toxic against two cancer cell lines. Moreover, SDEPN in combination with cisplatin induces a synergistic increase in the cell death of both HT29 and HepG2 cells.
文摘Flaxseed (Linum usitatissimum L.) is composed mainly of bioactive components such as polyphenols, polyunsaturated fatty acids, fiber and lignans. Flaxseed can be found in different presentation forms (grain or flour) and varieties (brown or golden);however, questions have arisen as to whether the presentation form and/or variety may influence the health effects. The objective of this study was to evaluate the effects on blood pressure, anthropometric and oxidative parameters in healthy human volunteers. All subjects received 40 gram aliquots of flaxseed and were instructed to consume them in their entirety mixed with water in the morning for a period of 14 days. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins via dietary intervention with golden flaxseed grains. There were no significant differences in anthropometric parameters, blood pressure, DNA damage and micronuclei frequency after 14-day supplementation. This research indicates that golden flaxseed grains can be a valuable adjunct for disease prevention and protecting the organism against oxidative damage.
