Marne Vasconcellos - Academia.edu (original) (raw)

Papers by Marne Vasconcellos

Biomaterials in Regenerative Medicine [Working Title]

In dentistry, biomaterials are used in restorative procedures, such as dental restorations; in de... more In dentistry, biomaterials are used in restorative procedures, such as dental restorations; in dentures; dental implants; surgical procedures; and endodontic materials. Most dental biomaterials are classified as devices, including filling materials, diagnostic aids, cements, bonding agents, and implants, in addition to mouthwashes. In the field of health, the use of natural products for dental biomaterials and curing diseases has always emphasized, rather than depending on the conventional allopathic medicine. Brazil has an advantage in this market, because it has the greatest biodiversity in the world, especially in the Amazonian Region, and a genetic heritage of great potential for the development of new herbal products, especially in dentistry. Given the growth of products derived from medicinal plants in Brazil, it was necessary to implement a statute that covered the requirements for all medicines and biomaterials to ensure the quality, efficacy, and safety of these products. Thus, researches in dentistry have been developed with the aim of searching for new bioactive principles for the formulation of drugs with different types of applications, capable of acting in both preventive strategies and curative treatments. This has encouraged the use of phytotherapic agents such as Copaifera multijuga, Apis mellifera (propolis), and Libidibia ferrea.

Química Nova, 2017

Piquiá (Caryocar villosum-Caryocaraceae) is a native fruit from the Amazon region rich in bioacti... more Piquiá (Caryocar villosum-Caryocaraceae) is a native fruit from the Amazon region rich in bioactive substances. Fruit pulp extracts were analyzed by HPLC, together with extracts obtained from fruit pulp industry residual parts, byproducts such as husks (shells) and seeds. Extracts were prepared with two ethanolic solvent systems. Phenolic substances ellagic and gallic acids were detected with standards and quantified by HPLC. Cytotoxic, antioxidant and anti-inflammatory activities in vitro were also evaluated. Shell extracts showed free radicals scavenger capacity in ABTS (IC 50 : 3.93 ± 0.12 µg mL-1) and DPPH models (IC 50 : 7.81 ± 0.34 µg mL-1), low cytotoxicity in human fibroblasts, but high at tumor strains, and also a high anti-inflammatory potential observed by the inhibition of nitric oxide production. At low concentrations (20 µg mL-1), excellent antioxidant activities were verified in cellular assays, with percentages of 70.69 ± 2.77%, 79.89 ± 6.50% and 79.48 ± 8.6% for shell, pulp and seed extracts, respectively. With this set of results, C. villosum fruit extracts become a high potential raw material to be used in pharmaceutical and cosmetic applications.

Bioorganic & medicinal chemistry letters, Jan 15, 2014

Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and i... more Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and in vivo antimalarial properties that are comparable to those of the control drug chloroquine in a mouse malaria model. Ellipticine derivatives and analogs exhibit antimalarial potential however only a few have been studied to date. Herein, ellipticine and a structural analog were isolated from Aspidosperma vargasii bark. A-ring brominated and nitrated ellipticine derivatives exhibit good in vitro inhibition of Plasmodium falciparum K1 and 3D7 strains. Several of the compounds were found not to be toxic to human fetal lung fibroblasts. 9-Nitroellipticine (IC50=0.55μM) exhibits greater antiplasmodial activity than ellipticine. These results are further evidence of the antimalarial potential of ellipticine derivatives.

Methods in Pharmacology and Toxicology, 2014

The open dentistry journal, 2016

The role of dentin cleaning is to remove debris that may impair adaptation and marginal sealing, ... more The role of dentin cleaning is to remove debris that may impair adaptation and marginal sealing, quantitatively reducing microorganisms. The aim of this study was to investigate through scanning electron microscopy (SEM) the morphology of the dentin surface, cut and treated with copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP). Twenty four upper pre-molars teeth, divided into eight groups (n=3), were used: G1: no cleaning, G2: air/water spray, G3: 10% CO, G4: 10% CO + A, G5: 30% CO, G6: 30% CO + A, G7: 1% EP, G8: 2% Chlorhexidine. The specimens were dentin discs (1 mm Ø). The SEM photomicrographs were classified and the results were: G1 - Debris dentin on the entire image / countless microorganisms, G2 and G7 - 50-100 debris / countless microorganisms and G3, G4, G5, G6 and G8 - 0-50 debris / countable microorganisms (50-100 colonies). The present results suggest that copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP) have feas...

Revista Brasileira de Farmacognosia, 2016

Toxicology in Vitro, 2016

Cancer is a public health problem and the second leading cause of death worldwide. The incidence ... more Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma.

BMC Complementary and Alternative Medicine, 2016

Archives of Toxicology, Jun 23, 2010

BiXorin is a natural quinone isolated from Capraria biXora L. Previous studies demonstrated that ... more BiXorin is a natural quinone isolated from Capraria biXora L. Previous studies demonstrated that biXorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective eVects of biXorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using diVerent approaches. In the Salmonella/microsome assay, biXorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biXorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biXorin did not induce signiWcant mutagenic and recombinogenic eVects at the employed concentration range. In addition, the pre-treatment with biXorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H 2 O 2 ) in S. cerevisiae. In V79 mammalian cells, biXorin was cytotoxic at higher concentrations. Moreover, at low concentrations biXorin pre-treatment protected against H 2 O 2 -induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modiWed comet assay using DNA glycosylases. Our results suggest that biXorin cellular eVects are concentration dependent. At lower concentrations, biXorin has signiWcant antioxidant and protective eVects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H 2 O 2 in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biXorin is cytotoxic and genotoxic.

Biological Pharmaceutical Bulletin, Sep 1, 2007

Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed p... more Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.

BMC Complementary and Alternative Medicine, 2016

The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal... more The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal plants. Several of these plants are used by the local population for the treatment of diseases, many of those with probable anti-inflammatory effect. The aim of the present investigation was to evaluate the in vitro antioxidant and anti-peroxidases potential of the ethanol extracts of five plants from the Brazilian Amazon (Byrsonima japurensis, Calycophyllum spruceanum, Maytenus guyanensis, Passiflora nitida and Ptychopetalum olacoides). DPPH, ABTS, superoxide anion radical, singlet oxygen and the β-carotene bleaching methods were employed for characterization of free radical scavenging activity. Also, total polyphenols were determined. Antioxidant activities were evaluated using murine fibroblast NIH3T3 cell. Inhibition of HRP and MPO were evaluated using amplex red® as susbtract. The stem bark extracts of C. spruceanum and M. guyanensis provided the highest free radical scavenging activities. C. spruceanum exhibited IC50 = 7.5 ± 0.9, 5.0 ± 0.1, 18.2 ± 3.0 and 92.4 ± 24.8 μg/mL for DPPH(•), ABTS(+•), O2 (-•) and (1)O2 assays, respectively. P. olacoides and C. spruceanum extracts also inhibited free radicals formation in the cell-based assay. At a concentration of 100 μg/mL, the extracts of C. spruceanum, B. japurensis inhibited horseradish peroxidase by 62 and 50 %, respectively. C. spruceanum, M. guyanensis, B. japurensis also inhibited myeloperoxidase in 72, 67 and 56 %, respectively. This work supports the folk use these species that inhibited peroxidases and exhibited significant free radical scavenging and antioxidant activities what can be related to treatment of inflammation.

Toxicology in Vitro, Apr 30, 2008

Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen t... more Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen transport, but that in high amounts presents a significant risk of neurodegenerative disorders. The objective of this study was to evaluate the mutagenic potential of iron sulfate. The comet assay and chromosome aberration (CA) analysis were applied to determine the DNA-damaging and clastogenic effects of iron sulfate. Human lymphocytes were treated in the quiescent phase for the comet assay and proliferative phase during the G 1 , G 1 /S, S (pulses of 1 and 6 h), and G 2 phases of the cell cycle for CA analysis, with 1.25, 2.5 and 5 lg/mL concentrations of FeSO 4 Á 7H 2 O. All tested concentrations were cytotoxic and reduced significantly the mitotic index (MI) in all phases of the cell cycle. They also induced CA in G 1 , G 1 /S and S (pulses of 1 and 6 h) phases. Iron sulfate also induced polyploidy in cells treated during G 1 . In the comet assay, this metal did not induce significant DNA damage. Our results show that Fe causes alteration and inhibition of DNA synthesis only in proliferative cells, which explain the concomitant occurrence of mutagenicity and cytotoxicity, respectively, in the lymphocytes studied.

Malaria Journal, 2015

The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona... more The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71 % suppression of P. berghei parasitaemia versus untreated controls). Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present.

European journal of medicinal chemistry, Jan 26, 2015

A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated fo... more A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.

Zeitschrift Fur Naturforschung C a Journal of Biosciences, 2005

Capraria biflora L. (Scrophulariaceae) is a perennial shrub widely distributed in several countri... more Capraria biflora L. (Scrophulariaceae) is a perennial shrub widely distributed in several countries of tropical America. The present work verified the cytotoxic and antioxidant potential of biflorin, an o-naphthoquinone isolated from C. biflora collected in the northeast region of Brazil. The cytotoxicity was tested on three different animal cell models: mouse erythrocytes, sea urchin embryos and tumor cells, while the antioxidant activity was assayed by the thiocyanate method. Biflorin lacked activity on mouse erythrocytes as well as on the development of sea urchin eggs, but strongly inhibited the growth of all five tested tumor cell lines, especially the skin, breast and colon cancer cells with IC 50 of 0.40, 0.43 and 0.88 µg/ml for B16, MCF-7 and HCT-8, respectively. Biflorin also showed potent antioxidant activity against autoxidation of oleic acid in a water/alcohol system.

Journal of Electroanalytical Chemistry, 2015

Revista Brasileira de Farmacognosia, 2015

ABSTRACT In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf te... more ABSTRACT In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf teas are used in folk medicine to treat several inflammatory illnesses. In order to validate this medicinal application, we analyzed the acute toxicity and antioxidant, antiedematogenic and antinociceptive potentials of an aqueous extract of this species, using culture cells and animal models. The aqueous extract did not cause toxic effects on human lymphocytes in high concentration (400 μg/mL), neither on mice treated with high doses (5000 mg/kg) in an acute toxicity analysis by oral route, and also did not cause lesions in the gastric mucosa of animals treated with 300 mg/kg, which was the maximal dose used in the anti-inflammatory screening. The aqueous extract caused inhibition of inflammatory pain in formalin-induced paw licking test with all tested doses, 30, 100 and 300 mg/kg, and antiedematogenic activity at 100 and 300 mg/kg. Additionally, the aqueous extract presented statistically significant action on the release of nitric oxide by lipopolysaccharide-activated macrophages. These results and other previously observed preliminarily studies support the folk use of this species, and further investigation of its action mechanism by inhibition of COX-2 or related metabolite would be interesting.

International Journal of Pharmacy and Pharmaceutical Sciences

ABSTRACT

Biomaterials in Regenerative Medicine [Working Title]

In dentistry, biomaterials are used in restorative procedures, such as dental restorations; in de... more In dentistry, biomaterials are used in restorative procedures, such as dental restorations; in dentures; dental implants; surgical procedures; and endodontic materials. Most dental biomaterials are classified as devices, including filling materials, diagnostic aids, cements, bonding agents, and implants, in addition to mouthwashes. In the field of health, the use of natural products for dental biomaterials and curing diseases has always emphasized, rather than depending on the conventional allopathic medicine. Brazil has an advantage in this market, because it has the greatest biodiversity in the world, especially in the Amazonian Region, and a genetic heritage of great potential for the development of new herbal products, especially in dentistry. Given the growth of products derived from medicinal plants in Brazil, it was necessary to implement a statute that covered the requirements for all medicines and biomaterials to ensure the quality, efficacy, and safety of these products. Thus, researches in dentistry have been developed with the aim of searching for new bioactive principles for the formulation of drugs with different types of applications, capable of acting in both preventive strategies and curative treatments. This has encouraged the use of phytotherapic agents such as Copaifera multijuga, Apis mellifera (propolis), and Libidibia ferrea.

Química Nova, 2017

Piquiá (Caryocar villosum-Caryocaraceae) is a native fruit from the Amazon region rich in bioacti... more Piquiá (Caryocar villosum-Caryocaraceae) is a native fruit from the Amazon region rich in bioactive substances. Fruit pulp extracts were analyzed by HPLC, together with extracts obtained from fruit pulp industry residual parts, byproducts such as husks (shells) and seeds. Extracts were prepared with two ethanolic solvent systems. Phenolic substances ellagic and gallic acids were detected with standards and quantified by HPLC. Cytotoxic, antioxidant and anti-inflammatory activities in vitro were also evaluated. Shell extracts showed free radicals scavenger capacity in ABTS (IC 50 : 3.93 ± 0.12 µg mL-1) and DPPH models (IC 50 : 7.81 ± 0.34 µg mL-1), low cytotoxicity in human fibroblasts, but high at tumor strains, and also a high anti-inflammatory potential observed by the inhibition of nitric oxide production. At low concentrations (20 µg mL-1), excellent antioxidant activities were verified in cellular assays, with percentages of 70.69 ± 2.77%, 79.89 ± 6.50% and 79.48 ± 8.6% for shell, pulp and seed extracts, respectively. With this set of results, C. villosum fruit extracts become a high potential raw material to be used in pharmaceutical and cosmetic applications.

Bioorganic & medicinal chemistry letters, Jan 15, 2014

Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and i... more Ellipticine has been shown previously to exhibit excellent in vitro antiplasmodial activity and in vivo antimalarial properties that are comparable to those of the control drug chloroquine in a mouse malaria model. Ellipticine derivatives and analogs exhibit antimalarial potential however only a few have been studied to date. Herein, ellipticine and a structural analog were isolated from Aspidosperma vargasii bark. A-ring brominated and nitrated ellipticine derivatives exhibit good in vitro inhibition of Plasmodium falciparum K1 and 3D7 strains. Several of the compounds were found not to be toxic to human fetal lung fibroblasts. 9-Nitroellipticine (IC50=0.55μM) exhibits greater antiplasmodial activity than ellipticine. These results are further evidence of the antimalarial potential of ellipticine derivatives.

Methods in Pharmacology and Toxicology, 2014

The open dentistry journal, 2016

The role of dentin cleaning is to remove debris that may impair adaptation and marginal sealing, ... more The role of dentin cleaning is to remove debris that may impair adaptation and marginal sealing, quantitatively reducing microorganisms. The aim of this study was to investigate through scanning electron microscopy (SEM) the morphology of the dentin surface, cut and treated with copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP). Twenty four upper pre-molars teeth, divided into eight groups (n=3), were used: G1: no cleaning, G2: air/water spray, G3: 10% CO, G4: 10% CO + A, G5: 30% CO, G6: 30% CO + A, G7: 1% EP, G8: 2% Chlorhexidine. The specimens were dentin discs (1 mm Ø). The SEM photomicrographs were classified and the results were: G1 - Debris dentin on the entire image / countless microorganisms, G2 and G7 - 50-100 debris / countless microorganisms and G3, G4, G5, G6 and G8 - 0-50 debris / countable microorganisms (50-100 colonies). The present results suggest that copaiba oil emulsions (CO) and suspension of ethanol extract of propolis (EP) have feas...

Revista Brasileira de Farmacognosia, 2016

Toxicology in Vitro, 2016

Cancer is a public health problem and the second leading cause of death worldwide. The incidence ... more Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma.

BMC Complementary and Alternative Medicine, 2016

Archives of Toxicology, Jun 23, 2010

BiXorin is a natural quinone isolated from Capraria biXora L. Previous studies demonstrated that ... more BiXorin is a natural quinone isolated from Capraria biXora L. Previous studies demonstrated that biXorin inhibits in vitro and in vivo tumor cell growth and presents potent antioxidant activity. In this paper, we report concentration-dependent cytotoxic, genotoxic, antimutagenic, and protective eVects of biXorin on Salmonella tiphymurium, yeast Saccharomyces cerevisiae, and V79 mammalian cells, using diVerent approaches. In the Salmonella/microsome assay, biXorin was not mutagenic to TA97a TA98, TA100, and TA102 strains. However, biXorin was able to induce cytotoxicity in haploid S. cerevisiae cells in stationary and exponential phase growth. In diploid yeast cells, biXorin did not induce signiWcant mutagenic and recombinogenic eVects at the employed concentration range. In addition, the pre-treatment with biXorin prevented the mutagenic and recombinogenic events induced by hydrogen peroxide (H 2 O 2 ) in S. cerevisiae. In V79 mammalian cells, biXorin was cytotoxic at higher concentrations. Moreover, at low concentrations biXorin pre-treatment protected against H 2 O 2 -induced oxidative damage by reducing lipid peroxidation and DNA damage as evaluated by normal and modiWed comet assay using DNA glycosylases. Our results suggest that biXorin cellular eVects are concentration dependent. At lower concentrations, biXorin has signiWcant antioxidant and protective eVects against the cytotoxicity, genotoxicity, mutagenicity, and intracellular lipid peroxidation induced by H 2 O 2 in yeast and mammalian cells, which can be attributed to its hydroxyl radical-scavenging property. However, at higher concentrations, biXorin is cytotoxic and genotoxic.

Biological Pharmaceutical Bulletin, Sep 1, 2007

Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed p... more Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.

BMC Complementary and Alternative Medicine, 2016

The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal... more The Amazon is the largest rainforest in the world and is home to a rich biodiversity of medicinal plants. Several of these plants are used by the local population for the treatment of diseases, many of those with probable anti-inflammatory effect. The aim of the present investigation was to evaluate the in vitro antioxidant and anti-peroxidases potential of the ethanol extracts of five plants from the Brazilian Amazon (Byrsonima japurensis, Calycophyllum spruceanum, Maytenus guyanensis, Passiflora nitida and Ptychopetalum olacoides). DPPH, ABTS, superoxide anion radical, singlet oxygen and the β-carotene bleaching methods were employed for characterization of free radical scavenging activity. Also, total polyphenols were determined. Antioxidant activities were evaluated using murine fibroblast NIH3T3 cell. Inhibition of HRP and MPO were evaluated using amplex red® as susbtract. The stem bark extracts of C. spruceanum and M. guyanensis provided the highest free radical scavenging activities. C. spruceanum exhibited IC50 = 7.5 ± 0.9, 5.0 ± 0.1, 18.2 ± 3.0 and 92.4 ± 24.8 μg/mL for DPPH(•), ABTS(+•), O2 (-•) and (1)O2 assays, respectively. P. olacoides and C. spruceanum extracts also inhibited free radicals formation in the cell-based assay. At a concentration of 100 μg/mL, the extracts of C. spruceanum, B. japurensis inhibited horseradish peroxidase by 62 and 50 %, respectively. C. spruceanum, M. guyanensis, B. japurensis also inhibited myeloperoxidase in 72, 67 and 56 %, respectively. This work supports the folk use these species that inhibited peroxidases and exhibited significant free radical scavenging and antioxidant activities what can be related to treatment of inflammation.

Toxicology in Vitro, Apr 30, 2008

Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen t... more Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen transport, but that in high amounts presents a significant risk of neurodegenerative disorders. The objective of this study was to evaluate the mutagenic potential of iron sulfate. The comet assay and chromosome aberration (CA) analysis were applied to determine the DNA-damaging and clastogenic effects of iron sulfate. Human lymphocytes were treated in the quiescent phase for the comet assay and proliferative phase during the G 1 , G 1 /S, S (pulses of 1 and 6 h), and G 2 phases of the cell cycle for CA analysis, with 1.25, 2.5 and 5 lg/mL concentrations of FeSO 4 Á 7H 2 O. All tested concentrations were cytotoxic and reduced significantly the mitotic index (MI) in all phases of the cell cycle. They also induced CA in G 1 , G 1 /S and S (pulses of 1 and 6 h) phases. Iron sulfate also induced polyploidy in cells treated during G 1 . In the comet assay, this metal did not induce significant DNA damage. Our results show that Fe causes alteration and inhibition of DNA synthesis only in proliferative cells, which explain the concomitant occurrence of mutagenicity and cytotoxicity, respectively, in the lymphocytes studied.

Malaria Journal, 2015

The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona... more The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;28.2) and the most active in vivo (at doses of 250 mg/kg, 71 % suppression of P. berghei parasitaemia versus untreated controls). Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present.

European journal of medicinal chemistry, Jan 26, 2015

A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated fo... more A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.

Zeitschrift Fur Naturforschung C a Journal of Biosciences, 2005

Capraria biflora L. (Scrophulariaceae) is a perennial shrub widely distributed in several countri... more Capraria biflora L. (Scrophulariaceae) is a perennial shrub widely distributed in several countries of tropical America. The present work verified the cytotoxic and antioxidant potential of biflorin, an o-naphthoquinone isolated from C. biflora collected in the northeast region of Brazil. The cytotoxicity was tested on three different animal cell models: mouse erythrocytes, sea urchin embryos and tumor cells, while the antioxidant activity was assayed by the thiocyanate method. Biflorin lacked activity on mouse erythrocytes as well as on the development of sea urchin eggs, but strongly inhibited the growth of all five tested tumor cell lines, especially the skin, breast and colon cancer cells with IC 50 of 0.40, 0.43 and 0.88 µg/ml for B16, MCF-7 and HCT-8, respectively. Biflorin also showed potent antioxidant activity against autoxidation of oleic acid in a water/alcohol system.

Journal of Electroanalytical Chemistry, 2015

Revista Brasileira de Farmacognosia, 2015

ABSTRACT In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf te... more ABSTRACT In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf teas are used in folk medicine to treat several inflammatory illnesses. In order to validate this medicinal application, we analyzed the acute toxicity and antioxidant, antiedematogenic and antinociceptive potentials of an aqueous extract of this species, using culture cells and animal models. The aqueous extract did not cause toxic effects on human lymphocytes in high concentration (400 μg/mL), neither on mice treated with high doses (5000 mg/kg) in an acute toxicity analysis by oral route, and also did not cause lesions in the gastric mucosa of animals treated with 300 mg/kg, which was the maximal dose used in the anti-inflammatory screening. The aqueous extract caused inhibition of inflammatory pain in formalin-induced paw licking test with all tested doses, 30, 100 and 300 mg/kg, and antiedematogenic activity at 100 and 300 mg/kg. Additionally, the aqueous extract presented statistically significant action on the release of nitric oxide by lipopolysaccharide-activated macrophages. These results and other previously observed preliminarily studies support the folk use of this species, and further investigation of its action mechanism by inhibition of COX-2 or related metabolite would be interesting.

International Journal of Pharmacy and Pharmaceutical Sciences

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