RESUMO

Oenothein B (OeB), a dimeric ellagitannin with a macrocyclic structure, is reported to have beneficial effects, including antioxidant, antitumor, antiviral, and antimutagenic effects, on human health. Despite the remarkable properties of OeB, its role in neovascularization process has not yet been evaluated. Thus, this study aimed to evaluate the angiogenic activity of OeB using a chorioallantoic membrane (CAM) assay at different concentrations (6.25, 12.5, and 25 µg/µL), employing digital imaging and histological analysis. Furthermore, to elucidate the mechanisms by which OeB influences angiogenesis, we assessed the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM using immunohistochemical analysis. All concentrations of OeB significantly increased (p < 0.05) the percentage of vascularization as well as the levels of all the angiogenesis-associated parameters evaluated, indicating the pronounced pro-angiogenic activity of OeB. Our results showed that inflammation was one of the most relevant phenomena observed in CAM histology along with angiogenesis. In addition, a significant increase in VEGF and TNF-α levels was observed in all the CAMs compared to the negative control (p < 0.05). We suggest that OeB may induce the presence of inflammatory cells in CAM, leading to increased VEGF and TNF-α levels that result in the induction of angiogenesis. Therefore, OeB presents a favorable profile that could be further explored for the development of drugs for pro-angiogenic and tissue repair therapies.

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RESUMO

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

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RESUMO

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Assuntos

RESUMO

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair.

RESUMO

Pedunculagin (PD), an ellagitannin found in different plant species, possesses several pharmaceutical properties, including antitumor, antioxidant, gastroprotective, hepatoprotective, and anti-inflammatory properties. However, the effects of PD alone on DNA remain to be determined. The aim of this study was to investigate the potential cytotoxic, genotoxic, and antigenotoxic activities of PD isolated from Plinia cauliflora seeds using in silico and in vitro assays. To elucidate the biological activities of PD, in silico tools indicative of antioxidant, antineoplastic, and chemopreventive activities of PD were used. Subsequently, the mutagenic/antimutagenic effects of PD were later assessed using bacteria with the Ames test, and the cytotoxic, genotoxic, and antigenotoxic effects utilizing human lymphocytes as evidenced by trypan blue exclusion test and CometChip assay. In silico analysis indicated potential antioxidant, chemopreventive, free radical scavenger, and cytostatic activities of PD. In the Ames test, PD was found to be not mutagenic; however, this plant component protected DNA against damage-mediated by mutagens 4-nitroquinoline-1-oxide and sodium azide. Regarding human lymphocytes, PD alone was cytotoxic and genotoxic; however, it also reduced DNA damage induced by doxorubicin at co- and post-treatment. In conclusion, PD showed genotoxic, antigenotoxic and cytotoxic effects in human lymphocytes and antimutagenic effects in bacteria.

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BACKGROUND: Gemin D (GD) is an ellagitannin found in several plant species rich in phenolic compounds. Its many beneficial properties include antioxidant and antitumoral. OBJECTIVE: The present study assessed the genotoxicity, cytotoxicity, antigenotoxicity, and anticytotoxicity of GD by in vitro and in vivo assays. METHOD: The Ames mutagenicity assay in Salmonella typhimurium, Micronucleus and Comet tests in mice were used to evaluate the biological activities mentioned above. To assess the GD's protective effects against DNA damage induced by different mutagens we performed co-, pre- and/or post-treatment in these assays. RESULTS: There was no genotoxic effect of GD via Ames and Micronucleus tests, but in the Comet assay the highest dose induced DNA damage. This same highest dose presented a significant cytotoxicity in mice. In the antigenotoxicity, GD protected DNA against the action of 4-nitroquinoline-1-oxide and sodium azide by Ames test, and also against the harmful action of cyclophosphamide in pre- and co-treatment by Micronucleus and Comet tests, but it did not protect DNA in post-treatment. Regarding to anticytotoxicity, GD provoked an anticytotoxic effect only during pre-treatment. CONCLUSION: Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.

Assuntos

RESUMO

The objective of this study was to evaluate the antioxidant effect of the hydroalcoholic extract of pequi peel (HEPP) in rats after administration of doxorubicin (DOX). Were used 26 Wistar rats divided into four groups, which G1 (n=6) received water and saline solution (control group), G2 (n=7) HEPP and saline solution, G3 (n=7) water and DOX, and G4 (n=6) HEPP and DOX. The HEPP was administered by gavage for 10 days to G2 and G4 and water to G1 and G3. DOX and saline solution were administered intravenously on day seven after the start of the experiment, with the DOX (10mg kg-1) applied in G3 and G4, and saline solution 0.9% in G1 and G2. Were evaluated weight and mortality rate. Ten days after the start of the experiment were evaluated creatina kinase MB (CK-MB), troponin and myoglobin, and the rats were euthanized and evaluated morphologically. There was no difference between treatments in weight of animals (P>0.05). About the mortality rate an increase in group 2 was showed (P 0.05). The results of the qualitative test for the detection of CK-MB, troponin I and myoglobin in the four groups were negative and there were no macroscopic changes in different rat's organs of different groups. Multifocal and moderate to severe acute tubular necrosis in cortical and medullary regions of the kidneys was observed in all rats studied. DOX intravenous and in a one dose of 10mg kg-1 don't induce cardiac changes in rats and the HEPP in conditions here evaluated increase the rate of mortality of rats, which may be related to toxic substances in the peel of this fruit.

O objetivo deste estudo foi avaliar o efeito antioxidante do extrato hidroalcoolico da casca do pequi (EHCP) em ratos após a administração de doxorrubicina (DOX). Foram utilizados ratos da raça Wistar, distribuídos em quatro grupos, sendo que os animais do G1 (n=6) receberam água e solução salina (grupo controle), G2 (n=7) EHCP e solução salina, G3 (n=7) água e DOX e G4 (n=6) EHCP e DOX. O EHCP foi administrado por gavagem durante 10 dias aos ratos dos grupos G2 e G4 e água aos dos G1 e G3. DOX na dose de 10mg kg-1 e solução salina 0,9% foram administradas por via intravenosa no dia sete após o início do experimento aos animais de G3 e G4 e aos de G1 e G2, respectivamente. Foram avaliados peso e taxa de mortalidade. Dez dias após o início do experimento, foi avaliada a concentração sérica de creatina quinase MB (CK-MB), troponina e mioglobina, e os ratos foram submetidos à eutanásia e à avaliação anatomopatológica. Não houve diferença entre os tratamentos quanto ao peso dos animais (P 0,05). Com relação à taxa de mortalidade, houve aumento no grupo 2 (P 0,05). Os resultados do teste qualitativo para a detecção de CK-MB, troponina I e mioglobina nos quatro grupos foram negativos e não foram observadas alterações macroscópicas nos órgãos dos ratos dos diferentes grupos. Constatou-se necrose tubular aguda multifocal de intensidade moderada a acentuada nas regiões cortical e medular nos rins de todos os ratos avaliados. A DOX em dose única de 10mg kg-1 e via intravenosa não promove alterações cardíacas em ratos e o EHCP nas condições avaliadas aumenta o índice de mortalidade em ratos, o que pode estar relacionado a substâncias tóxicas presentes na casca desse fruto.

RESUMO

The objective of this study was to evaluate the antioxidant effect of the hydroalcoholic extract of pequi peel (HEPP) in rats after administration of doxorubicin (DOX). Were used 26 Wistar rats divided into four groups, which G1 (n=6) received water and saline solution (control group), G2 (n=7) HEPP and saline solution, G3 (n=7) water and DOX, and G4 (n=6) HEPP and DOX. The HEPP was administered by gavage for 10 days to G2 and G4 and water to G1 and G3. DOX and saline solution were administered intravenously on day seven after the start of the experiment, with the DOX (10mg kg-1) applied in G3 and G4, and saline solution 0.9% in G1 and G2. Were evaluated weight and mortality rate. Ten days after the start of the experiment were evaluated creatina kinase MB (CK-MB), troponin and myoglobin, and the rats were euthanized and evaluated morphologically. There was no difference between treatments in weight of animals (P>0.05). About the mortality rate an increase in group 2 was showed (P 0.05). The results of the qualitative test for the detection of CK-MB, troponin I and myoglobin in the four groups were negative and there were no macroscopic changes in different rat's organs of different groups. Multifocal and moderate to severe acute tubular necrosis in cortical and medullary regions of the kidneys was observed in all rats studied. DOX intravenous and in a one dose of 10mg kg-1 don't induce cardiac changes in rats and the HEPP in conditions here evaluated increase the rate of mortality of rats, which may be related to toxic substances in the peel of this fruit.

O objetivo deste estudo foi avaliar o efeito antioxidante do extrato hidroalcoolico da casca do pequi (EHCP) em ratos após a administração de doxorrubicina (DOX). Foram utilizados ratos da raça Wistar, distribuídos em quatro grupos, sendo que os animais do G1 (n=6) receberam água e solução salina (grupo controle), G2 (n=7) EHCP e solução salina, G3 (n=7) água e DOX e G4 (n=6) EHCP e DOX. O EHCP foi administrado por gavagem durante 10 dias aos ratos dos grupos G2 e G4 e água aos dos G1 e G3. DOX na dose de 10mg kg-1 e solução salina 0,9% foram administradas por via intravenosa no dia sete após o início do experimento aos animais de G3 e G4 e aos de G1 e G2, respectivamente. Foram avaliados peso e taxa de mortalidade. Dez dias após o início do experimento, foi avaliada a concentração sérica de creatina quinase MB (CK-MB), troponina e mioglobina, e os ratos foram submetidos à eutanásia e à avaliação anatomopatológica. Não houve diferença entre os tratamentos quanto ao peso dos animais (P 0,05). Com relação à taxa de mortalidade, houve aumento no grupo 2 (P 0,05). Os resultados do teste qualitativo para a detecção de CK-MB, troponina I e mioglobina nos quatro grupos foram negativos e não foram observadas alterações macroscópicas nos órgãos dos ratos dos diferentes grupos. Constatou-se necrose tubular aguda multifocal de intensidade moderada a acentuada nas regiões cortical e medular nos rins de todos os ratos avaliados. A DOX em dose única de 10mg kg-1 e via intravenosa não promove alterações cardíacas em ratos e o EHCP nas condições avaliadas aumenta o índice de mortalidade em ratos, o que pode estar relacionado a substâncias tóxicas presentes na casca desse fruto.

RESUMO

Fractions of Caryocar brasiliensis leaf and bark, tested as molluscicidal, fought the intermediary host of schistosomiasis. The ecological niche of this mollusk is related to water sources. Besides this, a fungitoxic action of the ethyl-acetate fraction (leaf) was verified, exhibiting high activity towards Paracoccidioides brasiliensis. The gill epithelium of Poecilia vivipara (Cyprinodontiformes, Poeciliidae) was used to test the toxicity of these fractions to animal cells. Quantitative analyses demonstrated a decrease in the density of chloride cells exposed to the leaf fractions and an increase in those exposed to bark fractions. The leaf and bark fractions induced a decrease in the area of the chloride cells (CC) in the gill filament. The perimeter of the CC did not suffer significant changes in face of these fractions. The aqueous fraction of the leaf is more toxic to the guaru. Bark fractions are less debilitating, and can be employed in the control of cell populations, showing high efficacy at it

Frações da folha e casca de pequi (Caryocar brasiliensis), testadas como moluscicidas, combateram o hospedeiro intermedário da esquistossomose. O nicho ecológico desse molusco está associado a mananciais de água. Além disso foi verificada a ação fungiotóxica da fração acetato de etila (folha), que apresentou elevada atividade frente ao fungo Paracoccidioides brasiliensis. Utilizou-se o epitélio branquial de Poecilia vivípara (Cyprinodontiformes, Poeciliidae), para testar a toxicidade dessas frações para células animais. Análises quantitativas demonstraram redução da densidade numérica das células de cloro expostas às frações da folha e aumento das expostas à casca. A folha e a casca causaram a redução da área das células de cloro (CC) no filamento branquial. O perímetro das CC não sofreu alteração significativa perante tais frações. A fração aquosa da folha foi mais tóxica ao guaru. Frações da casca são menos prejudiciais, podendo ser empregadas no controle de populações celulares, pois se mostraram muito eficazes

RESUMO

Fractions of Caryocar brasiliensis leaf and bark, tested as molluscicidal, fought the intermediary host of schistosomiasis. The ecological niche of this mollusk is related to water sources. Besides this, a fungitoxic action of the ethyl-acetate fraction (leaf) was verified, exhibiting high activity towards Paracoccidioides brasiliensis. The gill epithelium of Poecilia vivipara (Cyprinodontiformes, Poeciliidae) was used to test the toxicity of these fractions to animal cells. Quantitative analyses demonstrated a decrease in the density of chloride cells exposed to the leaf fractions and an increase in those exposed to bark fractions. The leaf and bark fractions induced a decrease in the area of the chloride cells (CC) in the gill filament. The perimeter of the CC did not suffer significant changes in face of these fractions. The aqueous fraction of the leaf is more toxic to the guaru. Bark fractions are less debilitating, and can be employed in the control of cell populations, showing high efficacy at it

Frações da folha e casca de pequi (Caryocar brasiliensis), testadas como moluscicidas, combateram o hospedeiro intermedário da esquistossomose. O nicho ecológico desse molusco está associado a mananciais de água. Além disso foi verificada a ação fungiotóxica da fração acetato de etila (folha), que apresentou elevada atividade frente ao fungo Paracoccidioides brasiliensis. Utilizou-se o epitélio branquial de Poecilia vivípara (Cyprinodontiformes, Poeciliidae), para testar a toxicidade dessas frações para células animais. Análises quantitativas demonstraram redução da densidade numérica das células de cloro expostas às frações da folha e aumento das expostas à casca. A folha e a casca causaram a redução da área das células de cloro (CC) no filamento branquial. O perímetro das CC não sofreu alteração significativa perante tais frações. A fração aquosa da folha foi mais tóxica ao guaru. Frações da casca são menos prejudiciais, podendo ser empregadas no controle de populações celulares, pois se mostraram muito eficazes

RESUMO

Ethanolic extracts from leaves of Hyptis ovalifolia, H. suaveolens, H. saxatilis, Hyptidendrum canum, Eugenia uniflora, E. dysenterica, Caryocar brasiliensis and Lafoensia pacari were investigated for their antifungal activity against dermatophytes. The most effective plants were H. ovalifolia and E. uniflora, while Trichophyton rubrum was the most sensitive among the four dermatophytes species evaluated. This study has demonstrated antifungal properties of Brazilian Cerrado plant extracts in "in vitro" assays.

A atividade antifúngica de extratos etanólicos de folhas de Hyptis ovalifolia, H. suaveolens, H. saxatilis, Hyptidendrum canum, Eugenia uniflora, E. dysenterica, Caryocar brasiliensis e Lafoensia pacari sobre isolados de dermatófitos foi verificada. Os extratos mais ativos foram os de H. ovalifolia e E. uniflora, enquanto que Trichophyton rubrum foi o dermatófito mais sensível a ação das plantas. Estes dados demonstram as propriedades antifúngicas de plantas do Cerrado em ensaios in vitro.