Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains re... more Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant andsensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.
Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disord... more Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we...
Malaria is an infectious disease of major worldwide clinical importance that causes a variety of ... more Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the
Vascular biology and the microcirculation 729 chronic Hepatitis C infection before initiation of ... more Vascular biology and the microcirculation 729 chronic Hepatitis C infection before initiation of antiviral therapy. Genotypes 1 and 3 were present in 10 patients each, none had cirrhosis. 10 patients were treated with the combination of Daclastavir und Sofosbuvir, 7 patients received Sofosbuvir/ Ledipasvir, 3 patients received Ombitasvir, Paritaprevir, Ritonavir and Dasabuvir. We assessed vascular function using flow-mediated-dilation of the brachial artery and several markers of vascular function, coagulation, inflammation and oxidative stress. Patients were assessed just before start of therapy and at 12 and 24 weeks after start of antiviral treatment. Results: Viral load dropped from a median of 1.3 * 106 copies to zero copies at end of therapy. ALT was also significantly reduced from a median of 99.53±55.31 to 27.89±12.51 at end of therapy (p<0.001). Fibroscan (ultrasound) assessment of the liver tissue did not significantly change after therapy. In contrast endothelial function (FMD) significantly improved from 9.4±5.2% to 11.5±5.8% at 12 weeks and 11.9±4.5% at 24 weeks (p=0.0309). We also found significant reductions for E-Selectin 68.7±21.4 to 58.4±21.8 ng/ml (p=0.0086) and VCAM 1512±549.4 to 1178±394.6 (p=0.0027). On the other hand we did not find significant changes for CRP and IL6 as markers of inflammation nor for PAI-1 and D-Dimer. Conclusion: Treatment of chronic hepatitis C infection with effective suppression of viral replication induced a significant increase in flow-mediated dilation (FMD) of the brachial artery as a measure of vascular function as well as reducing vascular adhesion molecules. This may explain the reduction in CV morbidity after successful therapy of chronic hep C with new direct antivirals.
Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains re... more Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant and -sensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.
As several studies have shown a link between T1D and liver disease we explored the hepatic altera... more As several studies have shown a link between T1D and liver disease we explored the hepatic alterations due to diabetes and the modulation of this complication by the metformin adjunct therapy. Fifty five Wistar rats were divided in three groups: control (CTL, n = 20), high-fat diet/streptozotocin induced diabetic (DM, n = 20) and diabetic treated with metformin plus insulin (DM + Met + Ins, n = 15). The biochemical parameters (%HbA1c, cholesterol, fructosamine, triglycerides, total proteins, bilirubin, urea, uric acid, and ALT, AST, ALP, GGT, and amylase activities) were analyzed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyze oxidative stress enzymes, the inflammatory marker MCP-1 and RAGE gene expression. Lipid peroxidation was assessed by TBARs. AGE deposition and RAGE protein expression were studied in the liver by fluorescence spectrophotometry and western blot, respectively. The ...
ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of sever... more ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of severe lung infection and sepsis. Because inflammation is usually associated with oxidative stress, we investigated the effect of ExoU on free radical production and antioxidant defense mechanisms during the course of P. aeruginosa infection. In an experimental model of acute pneumonia, ExoU accounted for increased lipid peroxidation in mice lungs as soon as 3 h after intratracheal instillation of PA103 P. aeruginosa strain. The contribution of airway cells to the generation of a redox imbalance was assessed by in vitro tests carried out with A549 airway epithelial cells. Cultures infected with the ExoU-producing PA103 P. aeruginosa strain produced significantly increased concentrations of lipid hydroperoxides, 8-isoprostane, reactive oxygen intermediates, peroxynitrite and nitric oxide (NO), when compared to cells infected with exoU-deficient mutants. Overproduction of NO by PA103-infected c...
Background Brain circulation disorders such as chronic cerebral hypoperfusion have been associate... more Background Brain circulation disorders such as chronic cerebral hypoperfusion have been associated with a decline in cognitive function during the development of dementia. Astrocytes together with microglia participate in the immune response in the CNS and make them potential sentinels in the brain parenchyma. In addition, astrocytes coverage integrity has been related to brain homeostasis. Currently, physical exercise has been proposed as an effective intervention to promote brain function improvement. However, the neuroprotective effects of early physical exercise on the astrocyte communication with the microcirculation and the microglial activation in a chronic cerebral hypoperfusion model are still unclear. The aim of this study was to investigate the impact of early intervention with physical exercise on cognition, brain microcirculatory, and inflammatory parameters in an experimental model of chronic cerebral hypoperfusion induced by permanent bilateral occlusion of the common...
This work studies the potential subacute toxicological effects of the aqueous extract of Bacchari... more This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.
We have previously demonstrated that the hydroalcoholic extract from Pterodon pubescens Benth. se... more We have previously demonstrated that the hydroalcoholic extract from Pterodon pubescens Benth. seeds (sucupira branca, Leguminosae) exhibits anti-arthritic activity and that its oleaginous extract (OEP) and PF1 fraction exhibit acute and topic anti-edematogenic activities. In this work, we studied the antinociceptive activity of OEP and its fractions on the acetic acid-induced abdominal constriction and formalin assays in SW male mice. OEP was obtained by ethanol extraction and its four fractions by sequential liquid-liquid extraction. PF2 GC/MS profile indicated it contains furane diterpenes derivatives of vouacapan and non-vouacapan compounds. The antinociceptive properties were demonstrated to OEP and predominantly to PF1 and PF2 by the writhing test. In the formalin assay, PF1 inhibited both phases and PF2 inhibited mainly the late one. Then, PF1 and PF2 seemed to present antinociceptive effects by different mechanisms, peripheral and/or central inhibitory ones, and showed maximum antinociceptive properties with very low doses, providing a rationale for its popular use in pain disorders.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branc... more We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branca, Leguminosae) seeds exhibit anti-arthritic activity. In the present work we show that the oleaginous extract obtained from P. pubescens seeds (OEP) exhibits acute or topic anti-edematogenic activity when tested in carrageenan-induced paw edema or in croton oil-induced ear edema assays, respectively. Four fractions were obtained from OEP by sequential liquid–liquid extraction. The anti-edematogenic properties were predominant in the hexanic fraction, which was further fractionated by HPLC, yielding three sub-fractions (PF1.1, PF1.2 and PF1.3). PF1.1 and PF1.3 showed potent acute and topic anti-edematogenic activity. The PF1.2 sub-fraction, although not active in the carrageenan assay, exhibited a potent anti-edematogenic activity in the croton oil-induced ear edema. This sub-fraction shows a maximum efficacy similar to indometacin in a lower dose. The PF1.1 sub-fraction presented a comp...
h i g h l i g h t s Cerebral malaria causes cognitive impairment in the survivors mice. Cerebral ... more h i g h l i g h t s Cerebral malaria causes cognitive impairment in the survivors mice. Cerebral malaria decrease BDNF protein levels in the hipocampus. Cerebral malaria does not alters AChE activity in the hippocampus.
This work studies the potential subacute toxicological effects of the aqueous extract of Bacchari... more This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.
Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may ... more Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed.
Microcirculation (New York, N.Y. : 1994), Nov 2, 2017
We investigated the acute effects of simvastatin on cerebral microvascular rarefaction and dysfun... more We investigated the acute effects of simvastatin on cerebral microvascular rarefaction and dysfunction in spontaneously hypertensive rats (SHRs). Male Wistar Kyoto rats (WKY) and SHRs were divided into 4 groups of 8 animals each: WKY-CTL and SHR-CTL, treated with 0.9% saline; and WKY+SIM and SHR+SIM, treated with simvastatin (30 mg/kg/day) for 3 days by gavage. Cerebral functional capillary density (FCD) was assessed by intravital fluorescence videomicroscopy. Microvascular cerebral blood flow (mCBF) before and after administration within the cranial window of angiotensin II (1 μM) was investigated using laser speckle contrast imaging. Cerebral FCD was reduced in SHR-CTL compared to WKY-CTL (p<0.05). Simvastatin increased cerebral FCD in SHRs compared to SHR-CTL (p<0.05). The mCBF was reduced in SHR-CTL compared to WKY-CTL (p<0.05), and simvastatin increased mCBF compared with SHR-CTL (p<0.05). Angiotensin II elicited a reduction of mCBF in SHR-CTL and increased mCBF in ...
Zika virus (ZIKV) caused significant public health concern, because of its association with conge... more Zika virus (ZIKV) caused significant public health concern, because of its association with congenital malformations, neurological disorders in adults and, more recently, with deaths. Considering the necessity to mitigate the cases ZIKV-associated diseases, antiviral interventions against this virus are an urgent necessity. Sofosbuvir, a drug in clinical use against Hepatitis C Virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 x 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90 % in different anatomical compartments, such as in blood plasma, spleen, kidney and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals, despite the...
Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains re... more Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant andsensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.
Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disord... more Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we...
Malaria is an infectious disease of major worldwide clinical importance that causes a variety of ... more Malaria is an infectious disease of major worldwide clinical importance that causes a variety of severe, or complicated, syndromes including cerebral malaria, which is often fatal. Leukocyte integrins are essential for host defense but also mediate physiologic responses of the innate and adaptive immune systems. We previously showed that targeted deletion of the
Vascular biology and the microcirculation 729 chronic Hepatitis C infection before initiation of ... more Vascular biology and the microcirculation 729 chronic Hepatitis C infection before initiation of antiviral therapy. Genotypes 1 and 3 were present in 10 patients each, none had cirrhosis. 10 patients were treated with the combination of Daclastavir und Sofosbuvir, 7 patients received Sofosbuvir/ Ledipasvir, 3 patients received Ombitasvir, Paritaprevir, Ritonavir and Dasabuvir. We assessed vascular function using flow-mediated-dilation of the brachial artery and several markers of vascular function, coagulation, inflammation and oxidative stress. Patients were assessed just before start of therapy and at 12 and 24 weeks after start of antiviral treatment. Results: Viral load dropped from a median of 1.3 * 106 copies to zero copies at end of therapy. ALT was also significantly reduced from a median of 99.53±55.31 to 27.89±12.51 at end of therapy (p<0.001). Fibroscan (ultrasound) assessment of the liver tissue did not significantly change after therapy. In contrast endothelial function (FMD) significantly improved from 9.4±5.2% to 11.5±5.8% at 12 weeks and 11.9±4.5% at 24 weeks (p=0.0309). We also found significant reductions for E-Selectin 68.7±21.4 to 58.4±21.8 ng/ml (p=0.0086) and VCAM 1512±549.4 to 1178±394.6 (p=0.0027). On the other hand we did not find significant changes for CRP and IL6 as markers of inflammation nor for PAI-1 and D-Dimer. Conclusion: Treatment of chronic hepatitis C infection with effective suppression of viral replication induced a significant increase in flow-mediated dilation (FMD) of the brachial artery as a measure of vascular function as well as reducing vascular adhesion molecules. This may explain the reduction in CV morbidity after successful therapy of chronic hep C with new direct antivirals.
Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains re... more Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant and -sensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.
As several studies have shown a link between T1D and liver disease we explored the hepatic altera... more As several studies have shown a link between T1D and liver disease we explored the hepatic alterations due to diabetes and the modulation of this complication by the metformin adjunct therapy. Fifty five Wistar rats were divided in three groups: control (CTL, n = 20), high-fat diet/streptozotocin induced diabetic (DM, n = 20) and diabetic treated with metformin plus insulin (DM + Met + Ins, n = 15). The biochemical parameters (%HbA1c, cholesterol, fructosamine, triglycerides, total proteins, bilirubin, urea, uric acid, and ALT, AST, ALP, GGT, and amylase activities) were analyzed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyze oxidative stress enzymes, the inflammatory marker MCP-1 and RAGE gene expression. Lipid peroxidation was assessed by TBARs. AGE deposition and RAGE protein expression were studied in the liver by fluorescence spectrophotometry and western blot, respectively. The ...
ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of sever... more ExoU is a potent proinflammatory toxin produced by Pseudomonas aeruginosa, a major agent of severe lung infection and sepsis. Because inflammation is usually associated with oxidative stress, we investigated the effect of ExoU on free radical production and antioxidant defense mechanisms during the course of P. aeruginosa infection. In an experimental model of acute pneumonia, ExoU accounted for increased lipid peroxidation in mice lungs as soon as 3 h after intratracheal instillation of PA103 P. aeruginosa strain. The contribution of airway cells to the generation of a redox imbalance was assessed by in vitro tests carried out with A549 airway epithelial cells. Cultures infected with the ExoU-producing PA103 P. aeruginosa strain produced significantly increased concentrations of lipid hydroperoxides, 8-isoprostane, reactive oxygen intermediates, peroxynitrite and nitric oxide (NO), when compared to cells infected with exoU-deficient mutants. Overproduction of NO by PA103-infected c...
Background Brain circulation disorders such as chronic cerebral hypoperfusion have been associate... more Background Brain circulation disorders such as chronic cerebral hypoperfusion have been associated with a decline in cognitive function during the development of dementia. Astrocytes together with microglia participate in the immune response in the CNS and make them potential sentinels in the brain parenchyma. In addition, astrocytes coverage integrity has been related to brain homeostasis. Currently, physical exercise has been proposed as an effective intervention to promote brain function improvement. However, the neuroprotective effects of early physical exercise on the astrocyte communication with the microcirculation and the microglial activation in a chronic cerebral hypoperfusion model are still unclear. The aim of this study was to investigate the impact of early intervention with physical exercise on cognition, brain microcirculatory, and inflammatory parameters in an experimental model of chronic cerebral hypoperfusion induced by permanent bilateral occlusion of the common...
This work studies the potential subacute toxicological effects of the aqueous extract of Bacchari... more This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.
We have previously demonstrated that the hydroalcoholic extract from Pterodon pubescens Benth. se... more We have previously demonstrated that the hydroalcoholic extract from Pterodon pubescens Benth. seeds (sucupira branca, Leguminosae) exhibits anti-arthritic activity and that its oleaginous extract (OEP) and PF1 fraction exhibit acute and topic anti-edematogenic activities. In this work, we studied the antinociceptive activity of OEP and its fractions on the acetic acid-induced abdominal constriction and formalin assays in SW male mice. OEP was obtained by ethanol extraction and its four fractions by sequential liquid-liquid extraction. PF2 GC/MS profile indicated it contains furane diterpenes derivatives of vouacapan and non-vouacapan compounds. The antinociceptive properties were demonstrated to OEP and predominantly to PF1 and PF2 by the writhing test. In the formalin assay, PF1 inhibited both phases and PF2 inhibited mainly the late one. Then, PF1 and PF2 seemed to present antinociceptive effects by different mechanisms, peripheral and/or central inhibitory ones, and showed maximum antinociceptive properties with very low doses, providing a rationale for its popular use in pain disorders.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branc... more We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branca, Leguminosae) seeds exhibit anti-arthritic activity. In the present work we show that the oleaginous extract obtained from P. pubescens seeds (OEP) exhibits acute or topic anti-edematogenic activity when tested in carrageenan-induced paw edema or in croton oil-induced ear edema assays, respectively. Four fractions were obtained from OEP by sequential liquid–liquid extraction. The anti-edematogenic properties were predominant in the hexanic fraction, which was further fractionated by HPLC, yielding three sub-fractions (PF1.1, PF1.2 and PF1.3). PF1.1 and PF1.3 showed potent acute and topic anti-edematogenic activity. The PF1.2 sub-fraction, although not active in the carrageenan assay, exhibited a potent anti-edematogenic activity in the croton oil-induced ear edema. This sub-fraction shows a maximum efficacy similar to indometacin in a lower dose. The PF1.1 sub-fraction presented a comp...
h i g h l i g h t s Cerebral malaria causes cognitive impairment in the survivors mice. Cerebral ... more h i g h l i g h t s Cerebral malaria causes cognitive impairment in the survivors mice. Cerebral malaria decrease BDNF protein levels in the hipocampus. Cerebral malaria does not alters AChE activity in the hippocampus.
This work studies the potential subacute toxicological effects of the aqueous extract of Bacchari... more This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.
Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may ... more Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed.
Microcirculation (New York, N.Y. : 1994), Nov 2, 2017
We investigated the acute effects of simvastatin on cerebral microvascular rarefaction and dysfun... more We investigated the acute effects of simvastatin on cerebral microvascular rarefaction and dysfunction in spontaneously hypertensive rats (SHRs). Male Wistar Kyoto rats (WKY) and SHRs were divided into 4 groups of 8 animals each: WKY-CTL and SHR-CTL, treated with 0.9% saline; and WKY+SIM and SHR+SIM, treated with simvastatin (30 mg/kg/day) for 3 days by gavage. Cerebral functional capillary density (FCD) was assessed by intravital fluorescence videomicroscopy. Microvascular cerebral blood flow (mCBF) before and after administration within the cranial window of angiotensin II (1 μM) was investigated using laser speckle contrast imaging. Cerebral FCD was reduced in SHR-CTL compared to WKY-CTL (p<0.05). Simvastatin increased cerebral FCD in SHRs compared to SHR-CTL (p<0.05). The mCBF was reduced in SHR-CTL compared to WKY-CTL (p<0.05), and simvastatin increased mCBF compared with SHR-CTL (p<0.05). Angiotensin II elicited a reduction of mCBF in SHR-CTL and increased mCBF in ...
Zika virus (ZIKV) caused significant public health concern, because of its association with conge... more Zika virus (ZIKV) caused significant public health concern, because of its association with congenital malformations, neurological disorders in adults and, more recently, with deaths. Considering the necessity to mitigate the cases ZIKV-associated diseases, antiviral interventions against this virus are an urgent necessity. Sofosbuvir, a drug in clinical use against Hepatitis C Virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 x 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90 % in different anatomical compartments, such as in blood plasma, spleen, kidney and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals, despite the...
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