Papers by Alexandre Ferraz
Popularmente conhecido por cogumelo-do-sol o Agaricus blazei Murril classe C, apresenta ocorrênci... more Popularmente conhecido por cogumelo-do-sol o Agaricus blazei Murril classe C, apresenta ocorrência natural no sul do Estado de São Paulo. O cultivo comercial dessa espécie tem sido motivo de várias pesquisas devido seu valor nutricional e potencial terapêutico. Este estudo procura avaliar fitoquimicamente os principais ativos do extrato Agaricus blazei Murril classe C, bem como seu poder antioxidante in vitro e suas prováveis aplicações no tratamento de determinadas doenças. As análises fitoquímicas ocorreram por cromatografia de camada delgada e o potencial antioxidante foi avaliado pelo método enzimático da xantina oxidase (XO) na presença de extratos metanólicos do cogumelo em concentrações de 0, 1 mg/mL, 0, 25mg/mL, 0, 5 mg/mL, 1, 0 mg/mL e 2, 0 mg/mL, gerando os produtos estáveis derivados do radical hidroxila, 2, 3-DHBA e 2, 5-DHBA, que são detectáveis por CLAE (Cromatografia de Alta Eficiência). Os resultados obtidos pela análise das áreas dos picos cromatográficos do ensaio enzimático à base da XO demonstraram poder antioxidante em todas as concentrações dos extratos do cogumelo, sendo que, em 2, 0 mg/mL demonstra maior atividade, 64, 14 ± 0, 49%, com uma diferença de 52, 59 da menor dosagem. Saponinas, flavonóides e alcalóides foram encontrados em análises fitoquimicas do cogumelo Agaricus blazei Murril. Assim, esse cogumelo vem sendo amplamente utilizado no combate ao estresse físico, psicológico, imunoestimulante, no tratamento do diabetes, hipercolesterolemia e em alterações digestivas. Devido aos princípios fitoquímicos, sua utilização e potencial antioxidante, mais estudos necessitam ser realizados para comprovar sua efetividade e segurança no uso em humanos.
Journal of ethnopharmacology, Jan 31, 2017
Baccharis trinervis leaves are used in the traditional medicine for the treatment of high fevers,... more Baccharis trinervis leaves are used in the traditional medicine for the treatment of high fevers, edema, inflammation, sores and muscle cramps, snakebites and as antiseptics. To investigate the cytotoxic, genotoxic, and mutagenic effects of extracts and fractions of B. trinervis from Brazil and Colombia in Chinese Hamster Ovary (CHO) cells, as well as the mutagenic activity in Salmonella typhimurium. Aqueous extracts (AE) of aerial parts of B. trinervis from Brazil (B) and Colombia (C) were fractioned in ethyl acetate fraction (EAF), butanol extract (BF) and aqueous residue fraction (ARF). Qualitative chemical screening and determination of total flavonoid content were made. Identification of chemical constituents was performed by High Performance Liquid Chromatography (HPLC) and High Resolution Mass Spectrometry (HRMS). For the in vitro tests, CHO cells were treated for 3hours with extracts and fractions of B. trinervis. The cytotoxic activity was evaluated by clonal survival and 3...
Drug and chemical toxicology, 2017
Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions f... more Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide...
British Journal of Pharmaceutical Research, 2016
International Archives of Medicine, 2016
Cancer is one of the most leading causes of death worldwide. Morinda citrifolia was reported to h... more Cancer is one of the most leading causes of death worldwide. Morinda citrifolia was reported to have antitumor effects. Cisplatin (CDDP), Doxorubicin (DOX) and Cyclophosphamid (CPA) are the known effective chemotherapeutics, despite of having several side effects. This study evaluated antitumoral and oxidative effects of the aqueous extract of the fruit of M. critrifolia (AEMC) (15, 30, 60 and 120 µg/mL) in comparision to CDDP (1 and 5 μg/mL), CPA (20 μg/mL), DOX (2 μg/mL) and CPA + DOX (20:2 μg/mL) in Sarcoma 180 cells and Saccharomyces cerevisiae, respectively. Cytogenetic damage and DNA fragmentation were evaluated with cytokinesis-block micronucleus assay and comet assay, respectively. In addition, S. cerevisiae strains were used in oxidative damage evaluation. AEMC induced cytogenetic damage with the increased formation of micronuclei, nuclear buds and nucleoplasmic bridges compared to the antineoplastics tested. AEMC at 120 µg/ mL induced significant (p<0.05) DNA damage in Sarcoma 180 cells similar to the CDDP, as well as oxidative damage in S. cerevisiae strain deficient in mitochondrial superoxide dismutase (Sod2∆) and cytosolic catalase (Cat1∆). The bioactive compounds present in AEMC such as gallic, caffeic, chlorogenic, ellagic acid and rutin might be responsible for AEMC's antitumoral activity.
Journal of Toxicology and Environmental Health, Part A, 2015
Arrabidaea chica Verlot (Bignoniaceae) has been used as a medicinal herb to treat anemia, hemorrh... more Arrabidaea chica Verlot (Bignoniaceae) has been used as a medicinal herb to treat anemia, hemorrhage, inflammation, intestinal colic, hepatitis, and skin infections in the Brazilian Amazon region. Studies have demonstrated the healing properties of extracts obtained from A. chica leaves, which contain anthocyanins and flavonoids. However, few investigations have assessed the safe use of this plant species. In this study, mutagenic and genotoxic effects of a crude aqueous extract, a butanolic fraction, and aqueous waste from A. chica leaves were evaluated using the Salmonella/microsome assay in TA98, TA97a, TA100, TA102, and TA1535 strains and the alkaline comet assay in Chinese hamster ovary (CHO) cell culture with and without metabolic activation. The crude aqueous extract, butanolic fraction, and aqueous waste were not mutagenic in any of the Salmonella typhimurium strains tested, and showed negative responses for genotoxicity in CHO cells. High-performance liquid chromatography (HPLC) analysis indicated the presence of phenolic acids and flavonoids such as rutin and luteolin. The lack of mutagenic/genotoxic effects might be due to phytochemical composition with high concentrations of known anti-inflammatory compounds. Thus, the crude aqueous extract, butanolic fraction, and aqueous waste from A. chica leaves do not appear to pose short-term genotoxic risks.
Neuropharmacology, 2005
A crude (ECH) and a purified cyclohexane extract (HCP) of Hypericum caprifoliatum and their main ... more A crude (ECH) and a purified cyclohexane extract (HCP) of Hypericum caprifoliatum and their main phloroglucinol derivative (HC1) were evaluated regarding their action on monoaminergic systems, more precisely on dopamine. In rats and mice forced swimming test, ECH and HCP dose-dependently reduced the immobility time. The effect of the highest dose was prevented by a prior administration of either sulpiride or SCH 23390 (D(2) and D(1) dopamine receptor antagonist, respectively). HCP (360 mg/kg) decreased the locomotor activity of mice. ECH (90 mg/kg) caused hypothermia and potentiated apomorphine-induced (16 mg/kg) hypothermia in mice. HCP and HC1 inhibited, in a concentration-dependent and monophasic manner, the [(3)H]-DA, [(3)H]-NA and [(3)H]-5HT synaptosomal uptakes, but did not prevent the binding of specific ligands to the monoamine transporters. Moreover, when tested at the concentrations corresponding to its IC(50) on [(3)H]-DA uptake, HC1 did not induce a significant [(3)H]-DA release, while at a higher concentration (200 ng/ml) it enhanced significantly (by 12%) the synaptosomal DA release. These data suggest that the antidepressant-like effect of H. caprifoliatum on the forced swimming test is due to an increase in monoaminergic transmission, resulting from monoamine uptake inhibition, more potently of dopamine, which may be related to their phloroglucinol contents.
Dando continuidade ao trabalho de investigação química e farmacológica de espécies do gênero Hype... more Dando continuidade ao trabalho de investigação química e farmacológica de espécies do gênero Hypericum, foram investigados H. polyanthemum e H. myrianthum. O interesse pelas espécies do gênero Hypericum (família Guttiferae) deve-se a presença de produtos como hipericina, com importante atividade sobre vários retrovírus, in vitro e in vivo, em particular sobre o HIV. Além das hipericinas, as espécies do gênero apresentam flavonóides, xantonas e floroglucinois. A espécie mais conhecida é H. perforatum, amplamente utilizada como antidepressiva. Trabalhos recentes têm atribuído essa atividade à hiperforina, um derivado de floroglucinol. Este trabalho visou o isolamento dos constituintes químicos presentes no extrato éter de petróleo das duas espécies acima citadas. De H. polyanthemum foram isolados três benzopiranos de estrutura inédita (5,7-dimetoxi-2,2dimetil-6-isobutiril benzopirano;2,2-dimetil-7-hidroxi-6-isobutiril-5-metoxi benzopirano; 2,2-dimetil-5-hidroxi-6-isobutiril-7metoxi benzopirano). De H. myrianthum foi isolado um derivado de floroglucinol. Outros produtos das duas espécies estão sendo isolados.
Ecotoxicology and Environmental Safety, 2015
The processing and combustion of coal in thermal power plants release anthropogenic chemicals int... more The processing and combustion of coal in thermal power plants release anthropogenic chemicals into the environment. Baccharis trimera is a common plant used in folk medicine that grows readily in soils degraded by coal mining activities. This shrub bioaccumulates metals released into the environment, and thus its consumption may be harmful to health. The purpose of this study was to investigate the phytochemical profile, antioxidant capacity (DPPH), genotoxic (comet assay) and mutagenic potential (CBMN-cyt) in V79 cells of B. trimera aqueous extracts in the coal-mining region of Candiota (Bt-AEC), and in Bagé, a city that does not experience the effects of exposure to coal (Bt-AEB, a reference site). In the comet assay, only Bt-AEC was genotoxic at the highest doses (0.8 mg/mL and 1.6 mg/mL), compared to the control. For extracts from both areas, mutagenic effects were observed at higher concentrations compared to the control. The cell damage parameters were significantly high in both extracts; however, more striking values were observed for Bt-AEC, up to the dose of 0.8 mg/mL. In chemical analysis, no variation was observed in the contents of flavonoids and phenolic compounds, neither the antioxidant activity, which may suggest that DNA damage observed in V79 cells was induced by the presence of coal contaminants absorbed by the plant
Revista Brasileira de Farmacognosia, 2013
The aim of the present study was to determine neurobehavioral and genotoxic activities of ethanol... more The aim of the present study was to determine neurobehavioral and genotoxic activities of ethanol extract of Erythrina falcata Benth., Fabaceae, leaves on rats. Animals were treated with ethanol extract of E. falcata (100, 300 or 500 mg/ kg; i.p.) and the open field and elevated plus-maze tasks were used as behavioral models to investigate a possible effect on the locomotor and exploratory activity and anxiety, respectively. Genotoxic effect was investigated using the Comet assay. Ethanol extract of E. falcata leaves decreased the number of crossings and rearings in the open field task and increased the latency to start locomotion, though it was not able to affect habituation to apparatus measured 24 h after the first session. Behavioral parameters in the plus-maze test were not affected by E. falcata. Ethanol extract did not increase damage index and damage frequency in blood or brain, indicating no genotoxic effect. The results suggest that ethanol extract of E. falcata leaves was able to affect locomotion, exploration, and motivation of animals without anxiolytic/anxiogenic effect, indicating a possible depressant action on the central nervous system. Furthermore, the lack of DNA damage in brain is an indicative that ethanol extract of E. falcata leaves may not induce neurotoxic effects.
Planta Medica, 2008
In the present study we used the micronuclei test and the comet assay in mice to investigate the ... more In the present study we used the micronuclei test and the comet assay in mice to investigate the genotoxic and mutagenic effects of three benzopyrans--6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1); 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2); and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3)--isolated from Hypericum polyanthemum. No significant difference in polychromatic erythrocyte (PCE) percentage between the vehicle group and groups treated with HP1, HP2, or HP3 was detected, indicating no toxicity to the bone marrow of the animals. Only HP1 increased the frequency of micronucleated cells (MNPCEs) in bone marrow sampled after 24 h in comparison with the vehicle group, suggesting a weak mutagenic effect. The damage index and damage frequency did not show a significant increase after treatment with HP1, HP2, or HP3 in comparison with the vehicle group. The antitumor activity previously reported in vitro for these benzopyrans, the lack of acute toxicity, the MN induction only for HP1, and the relatively low DNA damage make all compounds good candidates for in vivo studies on antitumor action.
Phytotherapy Research, 2008
The antiproliferative activity of three benzopyrans isolated from the chloroform extract of the a... more The antiproliferative activity of three benzopyrans isolated from the chloroform extract of the aerial parts of Hypericum polyanthemum was analysed in order to determine their effect on the growth and cell cycle in the U-373 MG glioblastoma cell line. Compound 1 was less cytotoxic than compounds 2 and 3. A synergistic effect was noticed when the three benzopyrans were used simultaneously. The cytotoxicity noted could be related to an arrest in G2/M phase, leading to apoptosis in the U-373 MG glioblastoma cell line.
Phytomedicine, 2013
Cynara scolymus L., popularly known as artichoke, has been widely used in traditional medicine as... more Cynara scolymus L., popularly known as artichoke, has been widely used in traditional medicine as an herbal medicament for therapeutic purposes. The study aimed at assessing the protective activity of Cynara scolymus leaf extract (LE) against DNA lesions induced by the alkylating agent ethylmethnesulphonate (EMS) in Chinese hamster ovary cells (CHO). The ability of C. scolymus L. LE to modulate the mutagenicity of EMS was examined using the cytokinesis block micronucleus (CBMN) cytome assay in three antigenotoxic protocols, pre-post-and simultaneous treatments. In the pre-treatment, C. scolymus L. LE reduced the frequencies of MNi and NBUDs induced by EMS in the lower concentration. In contrast, at the highest concentration (5 mg/ml) artichoke enhanced the frequency of MNi, potentiating EMS genotoxicity. In the simultaneous treatment only the induction of MNi was repressed by the exposure of cells to C. scolymus L. LE. No modification in genotoxicity was observed in LE post-treatment. The results obtained in this study suggest that lower concentrations of artichoke prevent chemically induced genomic damage in mammalian cells. In this context, the protective activity of C. scolymus L. could be associated to its constitutive antioxidants compounds.
Pharmaceutical Biology, 2002
Organic and aqueous extracts of 145 Brazilian plants (538 extracts) from 34 families were evaluat... more Organic and aqueous extracts of 145 Brazilian plants (538 extracts) from 34 families were evaluated for anti-tumour activity against the human tumour cell lines HT29 and NCI-H460. Of the extracts tested, 117 (22%) demonstrated cytotoxicity against one or both of the cell lines at a concentration of 100 mg/ml. Of special interest are the families Anacardiaceae, Annonaceae, Asteraceae, Celestraceae, Leguminosae (Fabaceae), Meliaceae and Myrtaceae, which contain a high proportion of active species. On the basis of these results we are further examining the cytotoxic species, with the objective of isolating and identifying the active phytochemicals. These results also confirm the continuing importance of natural product screening models, alongside targeted drug development, in the discovery of new anti-neoplastic pharmacophores.
Pharmaceutical Biology, 2002
Aqueous and organic extracts of Asteraceae (Compositae) collected from the State of Rio Grande do... more Aqueous and organic extracts of Asteraceae (Compositae) collected from the State of Rio Grande do Sul, Brazil, have been tested in vitro for cytotoxic activity against human solid tumour cell lines. Twenty-five species, 125 extracts in total, were screened against HT29 human colon adenocarcinoma cells and NCI-H460 human non-small cell lung cancer cells. Twenty-five extracts from 11 species demonstrated cytotoxicity at 100 mg/ml against one or both of the cell lines tested. Further analysis was performed on the active extracts using three cell lines HT29, NCI-H460, and U373 human glioblastoma cells, to determine the IC 50 and the degree of tumour cell line selectivity. Extracts from Baccharis coridifolia, Baccharis ochracea, Eupatorium macrocephalum, Eupatorium pedunculosum and Stenachaenium riedelii all produced IC 50 values below 5 mg/ml. Comparison of the IC 50 results between cell lines identified that Baccharis coridifolia, Baccharis ochracea, Eupatorium laevigatum and Pluchea sagittalis extracts produced differential sensitivity across the panel of three cell lines. These species are currently under further investigation with the ultimate objective of isolation and identification of the active principles responsible for the anti-proliferative activity.
Journal of Photochemistry and Photobiology B: Biology, 2009
The photoprotective effect of the methanolic extracts of three Antarctic plant species-Deschampsi... more The photoprotective effect of the methanolic extracts of three Antarctic plant species-Deschampsia antarctica Desv., Colobanthus quitensis (Kunth) Bartl., and Polytrichum juniperinum Hedw. against UV-induced DNA damage was investigated in hamster lung fibroblasts (V79 cells) and in a biomonitor organism Helix aspersas, using comet assay. The protective, mutagenic, and antimutagenic profiles of these extracts were also evaluated using haploid strains of the simple eukaryote Saccharomyces cerevisiae, and antioxidant activity were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, as well as the hypoxanthine/xanthine oxidase assay. At the concentration range employed, the extracts were not cytotoxic or mutagenic to S. cerevisiae. In addition, the treatment with these extracts enhanced survival, and decreased induced reverse, frameshift, and forward mutations in a dose-response manner in all UVC doses employed. The plants extracts did not generate DNA strand breaks in V79 cells, and the treatment significantly decreased DNA damage induced by UVC. Extracts significantly decreased UVC-induced lipid peroxidation in V79 cells, showing a clear antioxidant property. Moreover, results of comet assay in V79 cells, employing Fpg, Endo III, and Endo V enzymes, demonstrated significant reduction of UVC-induced DNA damage after pre-incubation with these extracts. The treatment with all tested extracts were much less efficient against UVC-induced cytotoxicity in the yeast strain defective in photolyase as compared to the wild type strain, suggesting that this DNA repair pathway is stimulated by substances present in the extracts. All extracts showed a significant inhibitory effect in the hypoxanthine/xanthine oxidase assay, and they had the ability to scavenge DPPH. In H. aspersas, the treatment was able to protect against UVCinduced damage. In conclusion, D. antarctica, C. quitensis, and P. juniperinum extracts present photoprotective properties, which can be attributed to molecules, such as flavonoids and carotenoids, which act as UV-absorbing molecules and as antioxidants, as well as stimulate DNA-repair processes.
Journal of Medicinal Food, 2012
Cynara scolymus L. (Asteraceae), popularly known as artichoke, has been widely used in herbal med... more Cynara scolymus L. (Asteraceae), popularly known as artichoke, has been widely used in herbal medicine for the treatment of hepatic diseases. The genotoxicity of C. scolymus L. leaf extract (LE) and the ability to modulate the genetic toxicity of the alkylating agent ethyl methanesulfonate (EMS) were assessed using the comet assay on Chinese hamster ovary cells. Genotoxicity was evaluated after 1-and 24-h treatments using four different LE concentrations: 0.62, 1.25, 2.5, and 5.0 mg/mL. Antigenotoxicity was assessed for pretreatment, simultaneous treatment, and post-treatment. All doses used led to a significant increase in the frequency of DNA damage, after exposure for 1 and 24 h. In the antigenotoxicity experiments, LE reduced the frequency of DNA damage induced by EMS in the simultaneous treatment only. However, the lowest dose was more protective than higher concentrations. Flavonoids and phenolic compounds are, probably, the C. scolymus constituents responsible for its genotoxic and antigenotoxic effects.
Journal of Food Science, 2013
The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic... more The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic properties. However, few studies have assessed the possible toxic effects of artichoke extracts. This study evaluates genotoxic and mutagenic activities of artichoke leaf aqueous extract in mice using the comet assay and the micronucleus test. Leaf extracts were given by gavage (500 mg/kg, 1000 mg/kg, and 2000 mg/kg) for 3 consecutive days. Extract composition was investigated using phytochemical screening and high-performance liquid chromatography (HPLC). In addition, antioxidant capacity was analyzed through the diphenyl-picrylhydrazyl (DPPH) and xanthine oxidase assay. Phytochemical screening detected the presence of phenolic compounds, flavonoids, and saponins. HPLC analyses indicated the presence of chlorogenic acid, caffeic acid, isoquercetrin, and rutin. Extracts showed a dose-dependent free radical scavenging effect of DPPH and an inhibitory effect of xanthine oxidase. The genotoxic results showed that leaf extracts did not increase micronuclei in peripheral blood cells. Compared to the control group, a significant increase in comet assay values was observed only in bone marrow of group treated with 2000 mg/kg, the highest dose tested, indicating that artichoke tea should be consumed with moderation.
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Papers by Alexandre Ferraz