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Félix Alexandre Antunes Soares - One of the best experts on this subject based on the ideXlab platform.

  • guarana Paullinia cupana mart protects against amyloid β toxicity in caenorhabditis elegans through heat shock protein response activation
    Nutritional Neuroscience, 2020
    Co-Authors: D.c. Zamberlan, Ivana Beatrice Mânica Da Cruz, Leticia Priscilla Arantes, Marina Lopes Machado, Tassia Limana Da Silveira, Aline Franzen Da Silva, Claudia P Figueiredo, Félix Alexandre Antunes Soares
    Abstract:

    Alzheimer disease (AD) is a progressive neurodegenerative brain disorder that causes significant disruption in normal brain functioning, representing the most common cause of dementia in the elderly. The main hallmark of AD is the presence of amyloid plaques in the brain formed by the deposition of insoluble amyloid protein (Aβ) outside of neurons. Despite intensive investigation of the mechanisms of AD pathogenesis during the past three decades, little has been achieved in terms of effective treatments or ways to prevent the disease. Paullinia cupana, known as guarana, is a plant endemic to the Amazon region in Brazil with several beneficial effects reported, including delayed aging. In this study, we investigated the effects of chronic consumption of guarana ethanolic extract (GEE) on Aβ toxicity using a C. elegans model of AD. We analyzed the behavioral phenotype, oxidative damage and Aβ protein expression in worms treated with GEE. In addition, we investigated the possible role of the heat shock response on the beneficial effects induced by GEE. Overall, our data demonstrate that chronic GEE treatment decreased the formation of Aβ aggregates in C. elegans, preventing the behavioral deficits and the oxidative damage inducible by Aβ expression, due to activation of the heat shock protein (HSP) response. This finding provides a new alternative against amyloidogenic neurodegenerative diseases and other diseases caused by protein accumulation during aging.

  • guarana Paullinia cupana mart attenuates methylmercury induced toxicity in caenorhabditis elegans
    Toxicology Research, 2016
    Co-Authors: Leticia Priscilla Arantes, M. Aschner, Tanara V Peres, Pan Chen, Samuel W Caito, Félix Alexandre Antunes Soares
    Abstract:

    The influence of routine guarana (Paullinia cupana) consumption on apparent tolerance to mercury intoxication has been proposed. The present study investigated this hypothesis in Caenorhabditis elegans, a suitable experimental model for studies in toxicology. Wild type (WT) and skn-1 (ok2315) worm strains were pretreated with guarana ethanolic extract (GEE) from larvae 1 (L1) to L4 stage and then exposed for 6 hours to methylmercury (MeHg). The analyses included evaluation of GEE's effects on lethality, developmental delay, feeding, locomotion, gene expression (sod-3, gst-4, sir-2.1, hsf-1, snn-1, mtl-1, mtl-2, aat-1, aat-2 and aat-3) and antioxidant activity. GEE pre-treatment had no aberrant effects on WT worms exposed to MeHg, and protected skn-1 (ok2315) worms, which are more susceptible to environmental stresses. Protective effects of GEE might be dependent on modulation of genes other than those directly involved in antioxidant activity. GEE increased the expression of genes involved in metal transport (aat-2), metal detoxification (mtl-1 and mtl-2) and antioxidant responses (sir-2.1 and sod-3). Thus, routine consumption of guarana might be beneficial in protecting against MeHg-induced toxicity.

  • the protective effects of guarana extract Paullinia cupana on fibroblast nih 3t3 cells exposed to sodium nitroprusside
    Food and Chemical Toxicology, 2013
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, G Dos F F Santos, Margareth Linde Athayde
    Abstract:

    The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guarana has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

  • guarana Paullinia cupana kunth effects on ldl oxidation in elderly people an in vitro and in vivo study
    Lipids in Health and Disease, 2013
    Co-Authors: Rafael De Lima Portella, Ivana Beatrice Mânica Da Cruz, Euler Esteves Ribeiro, Rômulo Pillon Barcelos, Edovando José Flores Da Rosa, Leila Suleiman, Félix Alexandre Antunes Soares
    Abstract:

    Previous experimental investigations have suggested that guarana (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guarana on LDL and serum oxidation. The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guarana (GI) or never ingested guarana (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guarana in their diets. The LDL samples were exposed to 5 different guarana concentrations (0.05, 0.1, 0.5, 1, and 5 μg/mL). GI subjects demonstrated lower LDL oxidation than did NG subjects (reduction of 27%, p < 0.0014), independent of other variables. In the GI group the total polyphenols was positively associated with LDL levels. Also, guarana demonstrated a high antioxidant activity in vitro, mainly at concentrations of 1 and 5 μg/mL, demonstrated by suppression of CDs and TBARS productions, tryptophan destruction and high TRAP activity. Guarana, similar to other foods rich in caffeine and catechins such as green tea, has some effect on LDL oxidation that could partially explain the protective effects of this food in cardiometabolic diseases.

  • The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2012
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, G.f.f. Dos Santos, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, Margareth Linde Athayde
    Abstract:

    Abstract The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240 mg/g, theobromine = 6.733 mg/g and total catechins = 4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (

Heidi Dolder - One of the best experts on this subject based on the ideXlab platform.

  • Advantage of Guarana ́ (Paullinia cupana Mart.) Supplementation on Cadmium-induced Damages in Testis of Adult Wistar Rats
    2016
    Co-Authors: Rodrigo P Leite, Juliana Castro Monteiro, Karine Moura De Freitas, Ronaldo Seichi Wada, Fabrícia S. Predes, Heidi Dolder
    Abstract:

    Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported. On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days. Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significant decrease in the proportion of damaged seminiferous tubules. Also, P. cupana supplementation was effective in main-taining the number of Leydig cells per testis in the animals exposed to cadmium. In conclusion, P. cupana supplementation was partially efficient in preventing cadmium from damaging the testis of adult Wistar rats

  • advantage of guarana Paullinia cupana mart supplementation on cadmium induced damages in testis of adult wistar rats
    Toxicologic Pathology, 2013
    Co-Authors: Rodrigo P Leite, Fabricia De Souza Predes, Juliana Castro Monteiro, Karine Moura De Freitas, Ronaldo Seichi Wada, Heidi Dolder
    Abstract:

    Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported.  On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significa...

  • protective effect of guarana Paullinia cupana var sorbilis pre treatment on cadmium induced damages in adult wistar testis
    Biological Trace Element Research, 2011
    Co-Authors: Rodrigo P Leite, Fabricia De Souza Predes, Juliana Castro Monteiro, Ronaldo Seichi Wada, Heidi Dolder
    Abstract:

    Guarana (Paullinia cupana) is an Amazonian plant. Its antioxidant potential was demonstrated to be due to the high polyphenol concentration. On the other hand, one of the mechanisms underlying cadmium-induced cellular damage is free radical mediated, resulting in increased oxidative processes. This study investigated P. cupana’s potential to attenuate cadmium-induced damages in Wistar rat testis. Adult male Wistar rats were either pre-treated with 2 mg/g body weight (BW) of powdered P. cupana seed during 56 days and/or injected with cadmium chloride at a dose of 1.15 mg/kg BW. After cadmium exposition (48 h), testes samples were evaluated by histological and stereological analyses. Both groups exposed to cadmium presented evident morphological alterations relative to control animals. A few rodents showed massive cell death in the seminiferous epithelium and intertubular space, indicating that some animals are more sensitive to cadmium. Despite the alterations observed in both groups, pre-treatment with P. cupana was effective in attenuating morphological changes in Leydig cells, as well as reducing inflammatory response, relative to animals exclusively exposed to the metal. Animals treated only with P. cupana presented a significant increase in plasma testosterone levels and a significant increase in volumetric proportions of seminiferous tubules, which are indicative of spermatogenic stimulation.

Euler Esteves Ribeiro - One of the best experts on this subject based on the ideXlab platform.

  • guarana Paullinia cupana improves the proliferation and oxidative metabolism of senescent adipocyte stem cells derived from human lipoaspirates
    Food Research International, 2015
    Co-Authors: Alencar Machado, Fernanda Barbisan, Verônica Farina Azzolin, Marta Maria Medeiros Frescura Duarte, Francine Carla Cadoná, Eduardo Bortoluzzi Dornelles, Euler Esteves Ribeiro, Maria Fernanda Mânicacattani, Jose Raul Pinto Saldanha, Ivana Beatrice Mânica Da Cruz
    Abstract:

    Abstract Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mesenchymal stem cells, often making them unviable in regenerative clinical practice. In vitro supplementation by antioxidant food extract of senescent mesenchymal stem cells could reverse these undesirable characteristics. To evaluate this hypothesis, senescent adipocyte-mesenchymal cells (ASCs) obtained from human lipoaspirates were exposed at different concentrations of hydro-alcoholic guarana ( Paullinia cupana ) extract for 72 h. After the incubation, we performed a proliferative assay. Oxidative stress indicators and antioxidant enzymes (biochemical activity and gene expression by qRT-PCR analysis) in these senescent cells were also evaluated. In senescent cells exposed to guarana at 5 mg/g concentration increased cellular proliferation occurred compared to untreated senescent cells (79.1 ± 15.7%). Concomitantly, a decrease in several oxidative stress indicators was observed in senescent cells treated with guarana. A genomic effect of guarana exposure was observed when the modulation of antioxidant enzymes genes was analyzed. The results described here suggest that the food extract supplementation could reverse the initial senescence processes in ASCs. These results have potential application in regenerative medicine.

  • the protective effects of guarana extract Paullinia cupana on fibroblast nih 3t3 cells exposed to sodium nitroprusside
    Food and Chemical Toxicology, 2013
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, G Dos F F Santos, Margareth Linde Athayde
    Abstract:

    The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guarana has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

  • guarana Paullinia cupana kunth effects on ldl oxidation in elderly people an in vitro and in vivo study
    Lipids in Health and Disease, 2013
    Co-Authors: Rafael De Lima Portella, Ivana Beatrice Mânica Da Cruz, Euler Esteves Ribeiro, Rômulo Pillon Barcelos, Edovando José Flores Da Rosa, Leila Suleiman, Félix Alexandre Antunes Soares
    Abstract:

    Previous experimental investigations have suggested that guarana (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guarana on LDL and serum oxidation. The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guarana (GI) or never ingested guarana (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guarana in their diets. The LDL samples were exposed to 5 different guarana concentrations (0.05, 0.1, 0.5, 1, and 5 μg/mL). GI subjects demonstrated lower LDL oxidation than did NG subjects (reduction of 27%, p < 0.0014), independent of other variables. In the GI group the total polyphenols was positively associated with LDL levels. Also, guarana demonstrated a high antioxidant activity in vitro, mainly at concentrations of 1 and 5 μg/mL, demonstrated by suppression of CDs and TBARS productions, tryptophan destruction and high TRAP activity. Guarana, similar to other foods rich in caffeine and catechins such as green tea, has some effect on LDL oxidation that could partially explain the protective effects of this food in cardiometabolic diseases.

  • The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2012
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, G.f.f. Dos Santos, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, Margareth Linde Athayde
    Abstract:

    Abstract The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240 mg/g, theobromine = 6.733 mg/g and total catechins = 4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (

Margareth Linde Athayde - One of the best experts on this subject based on the ideXlab platform.

  • the protective effects of guarana extract Paullinia cupana on fibroblast nih 3t3 cells exposed to sodium nitroprusside
    Food and Chemical Toxicology, 2013
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, G Dos F F Santos, Margareth Linde Athayde
    Abstract:

    The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guarana has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.

  • The protective effects of guaraná extract (Paullinia cupana) on fibroblast NIH-3T3 cells exposed to sodium nitroprusside
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2012
    Co-Authors: L.s. Bittencourt, Fernanda Barbisan, Euler Esteves Ribeiro, Félix Alexandre Antunes Soares, Michel Mansur Machado, Denise Cantarelli Machado, G.f.f. Dos Santos, Thaís Doeler Algarve, Daniel Rodrigo Marinowic, Margareth Linde Athayde
    Abstract:

    Abstract The antioxidant effects of the hydro-alcoholic guarana extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guarana bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240 mg/g, theobromine = 6.733 mg/g and total catechins = 4.336 mg/g. Cells were exposed to 10 μM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guarana was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guarana antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guarana reverted the SNP toxicity mainly at lower concentrations (

Heidge Fukumasu - One of the best experts on this subject based on the ideXlab platform.

  • guarana Paullinia cupana controls the progression of 4 methylnitrosamino 1 3 pyridyl 1 butanone induced lung carcinogenesis in mice a role for inhibition of creb atf 1 activation
    Cancer Research, 2008
    Co-Authors: Heidge Fukumasu, Maria Lucia Zaidandagli
    Abstract:

    AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 5475 The needs of new agents or substances are urgent regarding cancer treatment and prevention. Guarana ( Paullinia cupana Mart. var. sorbilis ) was shown to present chemopreventive effect in a hepatocarcinogenesis model and growth control in Melanoma and Ehrlich tumor cells in vivo . It is known that tobacco consumption is the main cause of lung cancer, which is the most frequent cause of cancer deaths worldwide. The aim of this work was to study the chemopreventive effect of guarana on NNK-induced lung carcinogenesis. Sixty 42-day-old A/J female mice were injected with NNK (200mg/kg, I.P.), separated into three groups [CT, GA (100mg/kg) and GB (2000mg/kg)] and were treated up to 54 weeks with guarana mixed in powder ration. After euthanasia, lung lesions were counted, excised and fixed in formalin or snap frozen. Histopathology and morphometrical analyses were performed and immunohistochemistry for PCNA and phosphorylated CREB (Ser133) were conducted with DAB-LSAB method. At last, for statistical analysis non-parametric tests as Kruskal-Wallis or Mann-Whitney were used depending on the number of groups compared. Guarana (2000mg/kg) treatment after 52 weeks reduced body weight (CT=23.5±3.3, n=20; GA=24.2±2.5, n=19; GB=21.6±1.9g, n=21; p=0.009). All animals treated with NNK presented lung macroscopic lesions (CT=9.3±5.1; GA=12.3±3.5; GB=11.3±4.0; p=0.0604), and interestingly, a decreased percentage of lesions greater than 2.5mm were noted in guarana (GB) treated animals (CT=45.5±19.6%; GA=38.1±18.4%; GB=14.5±9.5%; p<0.0001). Histopathology and morphometrical analysis indicated that guarana reduced the malignancy of lung lesions (CT=1.7±0.4; GA=1.6±0.3; GB=1.5±0.3; p=0.0424) and led to a tendency of decreased tumor burden (CT=8.2±5.8%; GA=7.2±3.7%; GB=4.4±3.3%; p=0.0653). At a molecular level, guarana-treated animals presented lung tumors with less PCNA positive cells, indicating slower cell proliferation (CT=29.9±11.2%, n=6; GB=17.3±6.5%, n=7; p=0.0221). Accordingly, after phospho-CREB immunohistochemical analysis, which indicates that the transcription factor CREB/ATF-1 is in its active form, it was possible to note that guarana induced a growth control effect in lung tumor cells by reducing CREB activation (CT=63.9±5.6%, n=4; GB=47.0±5.2%, n=4; p=0.0286) and consequently control the progression of NNK-induced lung carcinogenesis. Our efforts are now directed to study which protein(s) phosphorylated CREB in these lung tumors as p38/MAPK, ERK1/2 and SAPK/JNK1, 2, 3 and identify the guarana targets responsible for such effects.

  • Paullinia cupana mart var sorbilis guarana reduces cell proliferation and increases apoptosis of b16 f10 melanoma lung metastases in mice
    Brazilian Journal of Medical and Biological Research, 2008
    Co-Authors: Heidge Fukumasu, Jose Luis Avanzo, Márcia Kazumi Nagamine, José Alexandre Marzagão Barbuto, Kurapati Venkata Kesava Rao, M L Dagli
    Abstract:

    We showed that guarana (Paullinia cupana Mart var. sorbilis) had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guarana in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5) cells/animal) were injected into the tail vein of mice on the 7th day of guarana treatment (2.0 mg P. cupana/g body weight, per gavage) and the animals were treated with guarana daily up to 14 days until euthanasia (total treatment time: 21 days). Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guarana-treated (GUA) animals presented a 68.6% reduction in tumor burden area compared to control (CO) animals which were not treated with guarana (CO: 0.84 +/- 0.26, N = 6; GUA: 0.27 +/- 0.24, N = 6; P = 0.0043), a 57.9% reduction in tumor proliferation index (CO: 23.75 +/- 20.54, N = 6; GUA: 9.99 +/- 3.93, N = 6; P = 0.026) and a 4.85-fold increase in apoptotic index (CO: 66.95 +/- 22.95, N = 6; GUA: 324.37 +/- 266.74 AB/mm(2), N = 6; P = 0.0152). In this mouse model, guarana treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guarana in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

  • protective effects of guarana Paullinia cupana mart var sorbilis against den induced dna damage on mouse liver
    Food and Chemical Toxicology, 2006
    Co-Authors: Heidge Fukumasu, Jose Luis Avanzo, Renato Heidor, Tereza Cristina Da Silva, A L Atroch, Fernando Salvador Moreno, M L Dagli
    Abstract:

    Guarana (Paullinia cupana Mart. var. Sorbilis) is a plant originally from Brazil, which is rich in tannins. Some tannins are known to present protective effects against DNA damage. This study was performed to investigate the anti-genotoxic/cytotoxic properties of guarana in hepatocytes of mice injected with N-nitrosodiethylamine (DEN). The protective effect of guarana was evaluated both by comet assay and DNA smear fragmentation technique in two month-old female BALB/c mice. These were treated previously with 2.0 mg/g bw of guarana for 16 days and then injected with DEN (160 microg/g body weight) to induce DNA damage. The DEN-only treated group presented higher comet image length than the guarana plus DEN and untreated groups (116.06+/-5.0 microm, 104.09+/-3.3 microm and 93.28+/-14.4 microm, respectively; p<0.01). Guarana treatment presented a 52.54% reduction in comet image length when animals were exposed to DEN (p<0.05). DNA samples from the guarana plus DEN group clearly showed less EtBr fluorescence intensity when compared to the DEN-only group, reinforcing the comet assay data. These results show, for the first time, that guarana has a protective effect against DEN-induced DNA damage in mouse liver.