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Different Passiflora species have been appointed as a promising herbal medicine due to antioxidant properties; however, their effect on oxidative process induced by diabetes is still controversial. We aimed to evaluate effects of hydroethanolic extract 70% from P. edulis leaf on biochemical blood markers, collagen glycation, production of oxidant species and platelet aggregation in diabetic rats. The phytochemical analysis of the extract was performed by dereplication using LC coupled to the Photodiode Array Detector and Mass Spectrometer detector. Male Wistar rats were assigned to the control group and groups treated with alloxan (150 mg/kg) intraperitoneally, extract (200 mg/kg/d, for 90 d) and combination of alloxan and extract. The phytochemical analysis suggested the presence of flavonoids C-glycosides in the extract. The diabetic animals treated with the extract presented improvement in glycaemic control, reduced glycation collagen, levels of non-high density lipoprotein (non-HDL) cholesterol, total cholesterol and creatinine, production of oxidant species and aggregation in platelet in relation to diabetic animals non-treated. Our results showed that P. edulis leaf extract presents a health benefit to the diabetic state, preventing the appearance of its complications. Its effect can be associated with flavonoids, among which is the flavonoid C-glycoside isoorientin.

In the original article, there was an error. The words "and T. catappa" should be removed. A correction has been made to Materials and Methods Section, under subsection Data processing, Paragraph Number: 3: "The 1H NMR and J-res projection spectra were previously stacked and then pre-processing according the following steps: baseline correction with the Whittaker Smoother option; apodization with Gaussian function of 1 GB [Hz]; normalization by the largest peak and smoothing Savitzky-Golay method. The processed NMR data were prepared using bin width of 0.04 ppm and the bin intensities method was average sum. Afterwards, the spectral data were saved with the peak intensities. Chemical shifts (δ) values were established between 0.0 and 10.0 ppm for S. marginata samples data and 0.0–13.0 ppm for B. intermedia." In the original article, there was an error. The words "and T. catappa" should be removed. A correction has been made to Discussion Section, Paragraph Number 1: "The analyses conducted for each set of samples using LC-HRMS and NMR showed that the extracts prepared from the leaves of the plant species B. intermedia and S. marginata had a comparable metabolite profile." In the original article, there weres errors. The words "and 90 compounds in the extracts of T. catappa" should be removed, and the reference to "Supplementary Table S7" should be “Supplementary Table S5." A correction has been made to Discussion Section, Paragraph Number 3: "The dereplication of the ESI-HRMS data using the macro database containing the Natural Products Dictionary (DNP) allowed a rapid and effective annotation of 68 compounds in the extracts of B. intermedia and 81 compounds in the extracts of S. marginata (see Supplementary Tables S4, S5)." In the original article, there was an error. The reference to "Supplementary Table S5" should be "Supplementary Table S4." A correction has been made to Discussion Section, Paragraph Number 4: "As mentioned previously in the results section, the metabolite profile of the hydroethanolic extracts of B. intermedia revealed that this plant is a rich source of cinnamic acids, phenolic acids derived from galloyl quinic and shikimic acid, proanthocyanidins, glycosylated flavonoids, triterpenes and other phenols (Supplementary Table S4)." In the original article, there was an error. A reference to "Supplementary Table S6" should be "Supplementary Table S5." A correction has been made to Discussion Section, Paragraph Number 8: "The extracts of S. marginata showed mainly exhibited compounds derived from saponins, glycosylated flavonoids, catechins and oligomeric proanthocyanidins (Supplementary Table S5). The detection of saponins in S. marginata in this study helped to confirm the findings reported in the literature which pointed out that saponins are the major class of compounds in this plant species (Heredia-Vieira et al., 2015). Precisely, the results of our study showed that triterpenic saponins were prevalent in the extracts of S. marginata; these compounds contained aglycones of oleanolic acid (olean-12-en-28-oic), hederagenin (3,23-dihydroxyolean-12-en-28-acid) and gypsogenin (3 hydroxy-23-oxo-olean-12-en-28-acid). The presence of glycosylated flavonoids was detected in three groups: C-glycosylated, C,O-glycosylated and O-glycosylated flavonoids (Supplementary Table S5). The compounds tetrastigma B (m/z 561.1603 [M+H]+, Rt = 9.89) and cassiaocidentalin A (m/z 561.1602 [M+H]+, Rt = 10.37) are examples of C,O glycosylated flavonoids isomers with an interglycosidic linkage between a deoxyhexose and 6-dideoxyhexose sugars (Heredia-Vieira et al., 2015). Two types of proanthocyanidin compounds were found in S. marginata; these included B-type and A-type proanthocyanidins (Supplementary Table S5). B-type proanthocyanidins are characterized by a single interflavan linkage between monomeric units which can be formed by the equivalent units of (epi)catechin. A-type proanthocyanidins, on the other hand, contain double interflavan bonds." The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Made available in DSpace on 2022-05-01T09:30:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Bauhinia holophylla leaves, also known as pata-de-vaca, are traditionally used in Brazil to treat diabetes. Although the hypoglycemic activity of this medicinal plant has already been described, the active compounds responsible for the hypoglycemic activity have not yet been identified. To rapidly obtain two fractions in large amounts compatible with further in vivo assay, the hydroalcoholic extract of B. holophylla leaves was fractionated by Vacuum Liquid Chromatography and then purified by medium pressure liquid chromatography combined with an in vivo Glucose Tolerance Test in diabetic mice. This approach resulted in the identification of eleven compounds (1-11), including an original non-cyanogenic cyanoglucoside derivative. The structures of the isolated compounds were elucidated by nuclear magnetic resonance and high-resolution mass spectrometry. One of the major compounds of the leaves, lithospermoside (3), exhibited strong hypoglycemic activity in diabetic mice at the doses of 10 and 20 mg/kg b.w. and prevents body weight loss. The proton nuclear magnetic resonance (1H NMR) quantification revealed that the hydroalcoholic leaves extract contained 1.7% of lithospermoside (3) and 3.1% of flavonoids. The NMR analysis also revealed the presence of a high amount of pinitol (4) (9.5%), a known compound possessing in vivo hypoglycemic activity. The hypoglycemic properties of the hydroalcoholic leaves extract and the traditional water infusion extracts of the leaves of B. holophylla seem thus to be the result of the activity of three unrelated classes of compounds. Such results support to some extent the traditional use of Bauhinia holophylla to treat diabetes. Faculty of Sciences São Paulo State University (UNESP), São Paulo School of Pharmaceutical Sciences University of Geneva Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO) University of Geneva Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University GC, Tehran Institute of Biociences São Paulo State University (UNESP), São Paulo Faculty of Sciences São Paulo State University (UNESP), São Paulo Institute of Biociences São Paulo State University (UNESP), São Paulo

Made available in DSpace on 2019-10-06T16:06:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Ethnopharmacological relevance: Virola elongata is a tree species belonging to the Myristicaceae family, distributed in the North and Midwest regions of Brazil, in the phytogeographic domain of the Amazon. The aqueous infusion or the hydroethanolic macerate of the stem bark of V. elongata are used in Brazilian and Ecuadorian indigenous folk medicine for several ethnopharmacological purposes, principally, in the treatment of stomach pain, indigestions, and gastric ulcers. This study was aimed to investigate the gastroprotective activity of this plant in order to support its popular use with scientific evidence. Materials and methods: The stem bark hydroethanolic extract of the plant (HEVe) was prepared by maceration. Its qualitative and quantitative phytochemical constituents were investigated by classical colorimetric techniques, HPLC, and electrospray ionization-multiple stage fragmentation (ESI-MSn). The gastroprotective and antiulcer activity of HEVe at doses of 100, 300 and 900 mg/kg p.o. were tested using three acute (acidified ethanol, piroxicam, and in-water-restrain stress), and one chronic (acetic acid) animal ulcer models. The probable mode of action of the HEVe was evaluated by analyzing gastric acid secretion, mucus content, nitric oxide effect, and its antioxidant properties (on catalase, myeloperoxidase, and GSH content) in experimental rodents. The direct extract's activity on the growth of Helicobacter pylori was also investigated. Results: Total phenolic content in the HEVe was of 146.20 ± 1.07 mg, being flavonoids about 50% (71.79 ± 0.70 mg) of it. Comparative HPLC fingerprint analysis revealed the presence of known phenolic antiulcer compounds, such as gallic acid, catechin, and rutin. Also, methanol/water fractionation and ESI-MSn analysis of the HEVe reveals the presence of quinic acid, 3,3′,4-trihydroxystilbene, juruenolid D, one catechin dimer, one C-glycosyl flavonoid, one polyketide and two neolignans as the major components of the extract. The HEVe attenuated gastric ulceration in all the different models of acute gastric ulcer, by enhancing gastroprotection through its antioxidant properties in vivo, and reducing also considerably the gastric secretion and total acidity. The HEVe also presented healing properties against the induced chronic ulceration process. On the other hand, the HEVe did not exhibit direct activity against H. pylori. Conclusion: The HEVe exhibited significant gastroprotective/antiulcer effects and contain a relative high proportion of phenolic compounds, especially flavonoids, that could likely account, at least in part, for its pharmacological properties. The results justify its traditional usage and provided scientific evidence for its potential as a new herbal medicine to treat gastric ulcers. Área de Farmacologia Departamento de Ciências Básicas em Saúde Universidade Federal de Mato Grosso (UFMT), Av. Fernando Correa da Costa, no. 2367 Curso de Farmácia Faculdade Noroeste do Mato Grosso Associação Juinense de Ensino Superior (AJES) Laboratório de Pesquisa de Produtos Naturais Faculdade de Medicina Universidade Federal de Tocantins (UFT) Laboratório de Bioprospecção de Produtos Naturais. Instituto de Biociências Universidade Estadual Paulista (UNESP) - Campus do Litoral Paulista Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP) - Campus Araraquara Laboratório de Bioprospecção de Produtos Naturais. Instituto de Biociências Universidade Estadual Paulista (UNESP) - Campus do Litoral Paulista Departamento de Química Orgânica Instituto de Química Universidade Estadual Paulista (UNESP) - Campus Araraquara CNPq: 132286/015-7 CAPES: 23038.000731/2013-56

Background/aim The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). Materials and methods Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks. Results Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05). Conclusion Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

The properties of oil-resin of copaiba, Copaifera multijuga are commonly mentioned in the literature, but there are few studies on extracts from its stem bark. We evaluated the antioxidant effects of ethanolic (EE) and ethyl acetate (EA) crude stem bark extracts from copaiba and compared them to rutin in a paracetamol (PCM)-induced oxidative stress model in mice. All test comparisons differed significantly. Hepatic catalase (CAT) and glutathione-S-transferase (GST) activity decreased in the PCM group, and there was an increase of protein carbonyls in the liver, kidney and brain. However, the protein carbonyls decreased in the liver for the PCM + EE group, in the kidneys for the PCM + EA and PCM + Rutin groups, and in the brain for all treatments. Hepatic GSH decreased in the PCM group and increased in the PCM + EE group. The extracts showed a positive effect on ascorbic acid (ASA), since they were able to restore the levels of parameters that had been changed by PCM. There was an increase of ALT and AST activity in the plasma within the PCM group. Even though ALT decreased in the PCM + Rutin, PCM + EE and PCM + EA groups, EE and EA did not have an effect on AST. The strongest antioxidant effect was observed for EE, due to the presence of the phenolic compounds epicatechin and epiafzelechin, as well as the highest concentration of total phenols and an excellent antioxidant potential observed in the DPPH· test. RESUMO As propriedades do óleo-resina da copaíba, Copaifera multijuga são comumente citadas na literatura, mas há poucos estudos sobre extratos da casca do caule. Avaliamos os efeitos antioxidantes de extratos brutos etanólico (EE) e acetato de etila (EA) da casca do caule da copaíba e os comparamos à rutina no modelo de estresse oxidativo induzido por paracetamol (PCM) em camundongos. Todas as comparações de teste diferiram significativamente. A atividade da catalase hepática (CAT) e da glutationa-S-transferase (GST) diminuiu no grupo PCM, e houve um aumento de proteínas carboniladas no fígado, rim e cérebro. No entanto, as proteínas carboniladas diminuíram no fígado no fígado para o grupo PCM + EE, nos rins para os grupos PCM + EA e PCM + rutina, e no cérebro para todos os tratamentos. A GSH hepática diminuiu no grupo PCM e aumentou no grupo PCM + EE. Os extratos mostraram um efeito positivo sobre o ácido ascórbico (ASA), uma vez que foram capazes de restaurar os níveis dos parâmetros que foram alterados pelo PCM. Houve um aumento da atividade de ALT e AST no plasma dentro do grupo PCM. Embora a ALT tenha diminuído nos grupos PCM + rutina, PCM + EE e PCM + EA, EE e EA não afetaram a AST. O efeito antioxidante mais forte foi observado para o EE, provavelmente devido à presença dos compostos fenólicos epicatequina e epiafzelequina, assim como à maior concentração de fenóis totais e um excelente potencial antioxidante observado no teste DPPH·.

Made available in DSpace on 2022-04-29T08:35:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods. Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy. A novel, surfactant-based ART-LUM formulation (S3AL), developed for transdermal delivery, may eliminate the shortcomings associated with oral delivery; namely poor drug absorption which is caused by the inherently low solubility of ART and LUM. Moreover, by successfully delivering these antimalarials transdermally, first-pass metabolism will be avoided leading to enhanced drug bioavailability in both cases. The S3AL formulation contained ART and LUM at equal concentrations (2.5% w/w of each) as well as Procetyl® AWS (30% w/w), oleic acid (10% w/w), 1-methyl-2-pyrrolidone (10% w/w), and water (45% w/w). The addition of LUM to the formulation changed the system from a striae structure to a dark field structure when visualized by a polarized light microscope. Additionally, this system possessed higher viscosity and superior skin bioadhesion, as evidenced by mechanical characterization, when compared to a similar formulation containing ART alone. S3AL was also proven to be biocompatible to human keratinocyte cells. Finally, in vitro studies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 295 µg cm-2 of ART and 94 13 µg cm-2 of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria. Graduate School of Bioscience and Technology of Bioactive Products Biology Institute University at Campinas, Sao Paulo School of Pharmacy Queen's University Belfast UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo Faculty of Pharmaceutical Science University at Campinas, Sao Paulo Centre for Information Technology 'Renato Archer' (CTI) 3D Printing Open Lab - Laprint, Sao Paulo Universidade de S o Paulo Departamento de Bot nica Instituto de Biociencias, Sao Paulo Faculdade de Ciencias Médicas Universidade Estadual de Campinas, Sao Paulo School of Mechanical Engineering University of Campinas, Sao Paulo UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente University of Calabar UNESP- University Estadual Paulista Faculdade de Ciencias Farmaceuticas UNESP, Sao Paulo UNESP Univ Estadual Paulista Instituto de Biociencias, Sao Vicente

Made available in DSpace on 2021-06-25T11:13:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-22 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31–1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole. Laboratory of Pharmacognosy Department of Pharmaceutical Sciences Faculty of Pharmacy Federal University of Rio Grande do Norte Laboratory of Bioprospecting of Natural Products São Paulo State University (UNESP) Laboratory of Phytochemistry Institute of Chemistry São Paulo State University (UNESP) Laboratory of Medical and Molecular Mycology Department of Clinical and Toxicological Analyses Federal University of Rio Grande do Norte Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar) Faculty of Pharmacy Federal University of Rio Grande do Norte Department of Health University Center of Maurício de Nassau Laboratory of Pharmacognosy Faculty of Pharmacy University Paris Descartes Laboratory of Bioprospecting of Natural Products São Paulo State University (UNESP) Laboratory of Phytochemistry Institute of Chemistry São Paulo State University (UNESP)

Made available in DSpace on 2021-06-25T10:33:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-10 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Ethnopharmacological relevance: Commiphora leptophloeos (Mart.) J.B. Gillett (Burseraceae) is a medicinal plant native from the brazilian northeast caatinga biome, known popularly as “imburana” or “imburana-de-cambão”. The leaves of C. leptophloeos are widely used in folk medicine in the treatment of various inflammatory disorders. However, there is no scientific evidence to justify their popular use. Aim of the study: This approach aimed to characterize the phytochemical profile of hydroethanolic leaf extract, as well as evaluate the anti-inflammatory and antioxidant potential activity and to investigate the acute toxicity with pre-clinical in vitro and in vivo methodologies. Materials and methods: The phytochemical profile was characterized by UPLC-MS and FIA-ESI-IT-MS/MS. The in vitro anti-inflammatory potential the hydroethanolic extract of C. leptophloeos (1, 10, 100 and 200 μg/mL) was investigated by lipopolysaccharide (LPS) induced nitric oxide assay, in order to analyze the potential decrease of nitric oxide (NO) production. For carrageenan-induced paw edema and zymosan-induced air pouch models, the extract (100, 200 and 400 mg/kg) was administrated by intragastric gavage (i.g.) route and used for evaluating the anti-inflammatory effect in vivo. Related to the first animal model, the antiedematogenic activity and myeloperoxidase (MPO) levels could be investigated. In addition, the zymosan-induced air pouch model allowed the analyses of leukocytes migration, total MPO, malondialdehyde (MDA) and cytokines (TNF-α and IL-10) levels. The toxicity in vitro of the extract (1, 10, 100 and 200 μg/mL) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute toxicity in vivo was tested using the extract at 2000 mg/kg by i. g. route. Results: The phytochemical analyses of C. leptophloeos leaf extract pointed the presence of six glycosylated flavonoids, identified as orientin, isoorientin, vitexin and isovitexin, quercetrin and isoquercitrin. A decrease of NO in vitro was noticed by the use of the extract in the LPS-induced nitric oxide assay and an expressive reduction of the paw-edema followed by a decrease of myeloperoxidase activity at doses of 200 and 400 mg/kg. The zymosan-induced air pouch model indicated that the extract, in all doses, significantly reduced the leukocytes migration, total protein concentration, MPO and MDA levels. The levels of cytokines were verified by the administration of extract in this model, revealing a lower of TNF-α level and an increase of the IL-10 production. In the toxicity study, the MTT assay evidenced no cytotoxicity of the tested concentrations and acute toxicity in vivo test did not result in any sign of toxicity and mortality or significant changes on the biochemical parameters. Conclusion: Based on these results, is possible suggest that the anti-inflammatory activity revealed in this approach can be related to the modulating the level of cytokine, decrease of TNF-α, increase of IL-10 in vivo and also the inhibition of the production of nitric oxide RAW 264.7 activated by LPS. These results demonstrate the potential anti-inflammatory effect C. leptophloeos leaf extrat in inflammatory in vivo models, supporting its use in folk medicine for treatment of inflammatory diseases. Finally, glycosylated flavonoids can be responsible, at least in part, for this effect. Research Group on Bioactive Natural Products (PNBio) Laboratory of Pharmacognosy Department of Pharmaceutical Sciences Faculty of Pharmacy Federal University of Rio Grande Do Norte Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar) Faculty of Pharmacy Federal University of Rio Grande Do Norte Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis Laboratory of Phytochemistry São Paulo State University (Unesp) Institute of Chemistry Araraquara, São Paulo Laboratory of Bioprospecting of Natural Products São Paulo State University (Unesp) Coastal Campus of São Vicente, São Vicente Laboratory of Microbiology and Immunology Department of Biology Federal Rural University of Pernambuco Rua Dom Manuel de Medeiros, S/N, Dois Irmãos Laboratory of Natural Polymers Biotechnology Department of Biochemistry Federal University of Rio Grande Do Norte, Avenue Salgado Filho Department of Biophysics and Pharmacology Biosciences Center Federal University of Rio Grande Do Norte, Avenue Salgado Filho, Natal Department of Health University Center of Maurício de Nassau, Fernando Lopes, 752 - Graças Laboratory of Phytochemistry São Paulo State University (Unesp) Institute of Chemistry Araraquara, São Paulo Laboratory of Bioprospecting of Natural Products São Paulo State University (Unesp) Coastal Campus of São Vicente, São Vicente

Made available in DSpace on 2021-06-25T10:56:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Ibervillea sonorae (Cucurbitaceae) is a medicinal plant utilized in Northwest Mexico against Diabetes and cancer. This natural product is taken orally, its presentation is capsules containing the plant's dried and powdered caudices. There is no regulation or standardized dosage that allows reproducibility of its pharmacological effects. Cucurbitacins are the main group of compounds found in I. sonorae and are known for their antiproliferative activity in cancer cells. Cucurbitacin IIb (CIIb), one of the compounds present in I. sonorae, has demonstrated in experimental models with HeLa cervical cancer cells an apoptotic and anti-tumoral activity. The objective of this study is to obtain and standardize two phytopreparations of I. sonorae based on their CIIb content, evaluate their antiproliferative activity in cancer cell lines, and compare the results with those obtained with CIIb; expecting to find phytopreparations with anti-cancer potential. APCI-IT-MSn is utilized for the identification of cucurbitacins, FT-ICR-MS/MS for the quantification of CIIb, and the MTT assay for the evaluation of the antiproliferative activity. The CIIb content was 0.67% for Fito-Ison-EtOH and 1.84% for Fito-Ison-EtOAc. In both phytopreparations, six cucurbitacins have been identified, and a seventh one not previously identified. Phytopreparations were more effective against HeLa, with IC50 of 30.0 and 18.6 µg/mL for Fito-Ison-EtOH and Fito-Ison-EtOAc, respectively. This effect is lower than observed on CIIb in HeLa (5.8 µg/mL). There are no significant differences (p > 0.05) in the antiproliferative activity between Fito-Ison-EtOAc and CIIb in A549, LS180, and MDA-MB-231 cells. Phytopreparations of I. sonorae have potential for the development of anti-cancer products. Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas, Araraquara – São Paulo, Brasil. Rodovia Araraquara – Jaú Km 1 Departamento de Ciencias Químico Biológicas y de la Salud Universidad de Sonora – Blvd. Luis Donaldo Colosio esq. Rosales S/N, Centro, Hermosillo Sonora Departamento de Ciencias Químico Biológicas y Agropecuarias Universidad de Sonora – Avenida Universidad e Irigoyen, Caborca Sonora Departamento de Medicina Universidad Panamericana – Augusto Rodin No. 498, Col. Insurgentes Mixcoac. Ciudad de México Universidade Estadual Paulista (UNESP) Coastal Campus of São Vicente, São Vicente, SP Praça Infante Dom Henrique s/n, CEP 11330-205 Universidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas, Araraquara – São Paulo, Brasil. Rodovia Araraquara – Jaú Km 1 Universidade Estadual Paulista (UNESP) Coastal Campus of São Vicente, São Vicente, SP Praça Infante Dom Henrique s/n, CEP 11330-205

Objectives This study was carried out to evaluate the effects of flavonoids present in leaves of Passiflora edulis fruit on complications induced by diabetes in rats. Methods The extract of P. edulis leaf was obtained by 70% ethanol maceration. From the dry extract, the fractions were obtained by consecutive liquid–liquid partition with hexane, ethyl acetate and n-butanol. The content of isoorientin of ethyl acetate and n-butanol fractions was determined by ultra-performance liquid chromatography coupled with electrospray and triple quadrupole ionization (TQD) analysis in tandem mass spectrometry (UPLC–ESI-Tq-MS). Only Fr-BuOH was used to treat diabetic or not Wistar rats. Biochemical parameters, platelet aggregation and production of reactive species were evaluated. Key findings The UPLC–ESI-Tq-MS analysis revealed the presence of several flavonoids, among which we identified five possible flavonoids c-heterosides (luteolin-7-O-pyranosyl-3-O-glucoside, apigenin-6-8-di-C-glycoside, apigenin-6-C-arabinoside-8-C-glycoside, isoorientin, isovitexin). The diabetic rats (treated intraperitoneally with alloxan, 150 mg/kg) treated with Fr-BuOH (20 mg/kg/day for 90 days) presented improvement in blood glucose, serum levels of fructosamine, lipid profile and urea. Furthermore, the Fr-BuOH reduced both platelet aggregation and the production of oxidant species in diabetic animals. Conclusions These results suggested that flavonoid C-glycosides present in the Fr-BuOH may be beneficial for the diabetic state, preventing complications induced by diabetes.

Made available in DSpace on 2020-12-12T02:01:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-28 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Ethnopharmacological relevance: Terminalia catappa L. (Combretaceae), known as “amendoeira da praia” in Brazil, has been recognized as a medicinal plant in folk medicine for the treatment of gastrointestinal disorders and other inflammatory conditions. The present study aimed to investigate the preventive and healing effects of the infusion of leaves of T. catappa (ILTC) against gastric lesions caused by ischemia and reperfusion (I/R) injury and characterize its mechanism of action in the gastric mucosa of rats. Materials and methods: Different doses (30, 100, and 300 mg/kg) of ILTC were orally administered as acute and subacute treatments against I/R-induced gastric lesion in rats. After treatment, the stomach of rats was collected to measure the lesion area, redox parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) and inflammatory parameters myeloperoxidase activity (MPO), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). The activities of matrix metalloproteinases 2 and 9 (MMPs 2 and 9) were assessed by zymography method to clarify the mechanisms of the healing acceleration promoted by ILTC. Results: Pretreatment with ILTC (100 mg/kg) was effective in preventing the aggravation of lesions in the acute model by reducing MPO activity by 38% relative to control group, despite the lack of clarity of this action at the macroscopical level at the lesion area (p < 0.05). After three days of treatment with ILTC (30 and 100 mg/kg), this infusion significantly reduced the lesion area by 95% and 89%, respectively, compared the control (p < 0.05). The gastric healing effect of all doses of ILTC was followed by a reduction in MPO activity (decrease by 70–78%). Compared to the negative control, an improvement in gastric healing owing to treatment with ILTC was observed and this was followed by an increase in MMP-2 (20–47%) (p < 0.05). Conclusion: Three days of treatment with ILTC could accelerate the healing process in I/R-induced lesions in rats. By decreasing MPO levels, ILTC enabled the action of MMP-2, which led to tissue recovery in the gastric mucosa. Department of Physiology Biosciences Institute UNESP-São Paulo State University, São Paulo Snyder Institute for Chronic Diseases Cumming School of Medicine University of Calgary Biosciences Institute UNESP-São Paulo State University, São Vicente, São Paulo Institute of Chemistry UNESP-São Paulo State University, São Paulo Laboratory of Extracellular Matrix UNESP- São Paulo State University, São Paulo Department of Physiology Biosciences Institute UNESP-São Paulo State University, São Paulo Biosciences Institute UNESP-São Paulo State University, São Vicente, São Paulo Institute of Chemistry UNESP-São Paulo State University, São Paulo Laboratory of Extracellular Matrix UNESP- São Paulo State University, São Paulo FAPESP: 2015/14797-3 CNPq: 301397/2017-1 CNPq: 306209/2016-0 CAPES: 88882.183585/2018-01 CAPES: 88882.183586/2018-01

Made available in DSpace on 2020-12-12T02:33:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 The aim of this study was to evaluate the therapeutic properties of Mimosa caesalpiniifolia in liver of rats exposed to cadmium under morphological, oxidative, inflammatory, and mutagenic parameters. A total of 40 Wistar rats (90 days, ~ 250 g) were distributed into eight groups (n = 5) as follows: (i) control; (ii) cadmium: cadmium chloride injection at 1.2 mg/kg; (iii) Mimosa extract: treatment with Mimosa extract at 250 mg/kg; (iv) Mimosa fraction: treatment with Mimosa acetate fraction at 62.5 mg/kg; (v) cadmium and Mimosa extract 62.5: submitted to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 62.5 mg/kg; (vi) cadmium and Mimosa extract 125: subjected to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 125 mg/kg; (vii) cadmium and Mimosa 250 extract: submitted to cadmium chloride 1.2 mg/kg injection and treatment with Mimosa extract at 250 mg/kg; (viii) cadmium treated with fraction of Mimosa acetate: submitted to cadmium chloride 1.2 mg/kg injection and treatment with acetate fraction of Mimosa extract at 62.5 mg/kg. In the animals intoxicated with cadmium and treated with fraction [62.5], increased expression of SOD-Mn reduced frequency of binucleated hepatocytes, karyolysis, and karyorrhexis, besides the antimutagenic and antioxidant action. The extract [62.5] was cytoprotective, antimutagenic, and reduced karyolysis. The extract [125] was cytoprotective, antioxidant, antifibrotic, anti-inflammatory, and reduced frequency of binucleated hepatocytes, while extract [250] was cytotoxic and mutagenic. In summary, the extract of Mimosa exerts some therapeutic properties in hepatic tissue after Cd intoxication, but only when it is administrated at intermediate doses. Probably, a high content of polyphenols in the EHM [250] and Fr-EtOAc groups exert pro-oxidant activities in the liver particularly when associated with Cd. Department of Biosciences Federal University of Sao Paulo UNIFESP, Rua Silva Jardim, 136 UNESP São Paulo State University, Coastal Campus UNESP São Paulo State University, Coastal Campus

Made available in DSpace on 2020-12-10T19:48:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-25 Unochapeco Ethnopharmacological importance: The species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is native to the Americas and is distributed widely throughout Brazil, where it is known as urtiga-brava, urtiga-vermelha, or urtigao. The leaves are often used as anti-inflammatory and antirheumatic agents and for the treatment of gastric disorders. However, the pharmacological mode of action underlying the gastroprotection induced by this species has not been investigated. Aim of the study: To contribute to the knowledge of the gastroprotective mode of action of the hydroalcoholic extract of U. baccifera (HEU) leaves. Materials and methods: Antiulcerogenic effect of HEU against ethanol-induced acute gastric ulcer was evaluated in rats and mice at doses of 3-300 mg/kg. NO-synthase inhibitor (L-NAME), SH blocker (NEM), cyclooxygenase inhibitor (indomethacin) and alpha 2-adrenergic receptor antagonist yohimbine were used to evaluate the participation of cytoprotective factors in HEU gastroprotection. Moreover, the levels of reduced gluthatione (GSH) and cytokines (TNF, IL-6, IL4 and IL-10), as well as the enzymatic activity of gluthatione S-transferase (GST), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) were measure. Moreover, the samples were analyzed histologically and the antisecretory capability of HEU were quantified using pylorus ligated rats. Results: The phytochemical analysis of HEU (UPLC/ESI-IT-MS) identified the flavonoids diosmetin and apigenin glucuronide. Furthermore, HEU decreased the occurrence of ethanol-induced ulcers at 30 and 300 mg/kg by 57% and 66%, respectively, compared with the vehicle. The gastroprotective effects were accompanied by increased GSH levels and GST and SOD activity as well as by reduced MPO activity in vivo and in vitro, revealing antioxidant effects and inhibition of neutrophil infiltration. The beneficial effects of 30 and 300 mg/kg HEU were also observed upon histological analyses. Regarding the mode of action, the gastroprotective effect of HEU was abolished by the pre-administration of L-NAME, NEM, indomethacin or yohimbine. Moreover, HEU was able to decrease the IL-6, IL-4 and IL-10 in ulcerated tissue, as well as the pepsin activity of the gastric juice in pylorus-ligated rats. Conclusion: Together, the results confirmed that the gastroprotection elicited by HEU was due reduction in oxidative damage, neutrophil migration, and peptic activity. This work validates the popular use of U. baccifera to treat gastric disorders and supports important future research for the identification of gastroprotective molecules from this species. Univ Comunitaria Regiao Chapeco, Programa Posgrad Ciencias Saude, BR-89809900 Chapeco, SC, Brazil Univ Estadual Paulista, Inst Biociencias, BR-70770901 Sao Vicente, SP, Brazil Univ Vale Itajai, Programa Posgrad Ciencias Farmaceut, BR-88302202 Itajai, SC, Brazil Univ Estadual Paulista, Inst Biociencias, BR-70770901 Sao Vicente, SP, Brazil

Made available in DSpace on 2020-12-12T01:46:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-05 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Estadual Paulista Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Isoorientin (ISOO) a glycosylated flavonoid found in acai berry exhibits relevant activities such as antidiabetic and antidepressant. However, its physicochemical action on any molecular target is scarcely known. In this work, we tackle the problem about the binding of ISOO to human serum albumin (HSA) applying fluorescence spectroscopy bimodal analysis aided by computational simulations. A static quenching process was detected having hypsochromic shift with implication in the polarizability around the endogenous probe (Trp 214) during complex formation. The binding mechanism reveals that all sites are equivalents and independents with binding constant value of 9.1 × 104 M-1 and, a total of six sites accessed whereas three of them were identified experimentally. The thermodynamic evaluation indicates that the complex formation is spontaneous (ΔG

Made available in DSpace on 2020-12-12T01:48:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Consejo Nacional de Ciencia y Tecnología The phytochemical profile, formulations (nanoparticles and gel), moisturizing and antioxidant potential of a hydroalcoholic fraction of Moringa oleifera leaves (HFM) were determined. These were obtained through the application of eco-friendly strategies of cultivation and processing. The HFM phytochemical analysis by ESI-IT-MSn showed the presence of seven compounds (flavonoids and phenolic acids). The viscosity, pH and particle size of HFM formulations ensure the suitability for topical application. Antioxidant activity was determined by inhibition of lipid peroxidation and ferric thiocyanate in vitro; it was confirmed that HFM and in formulations showed a significant inhibition of oxidation. In relation to the in vitro skin biophysical evaluation for topical formulations of HFM, water content, lipids and trans-epidermal water loss on the skin were favored with the presence of HFM. In addition, skin pH was not been modified. Our results emphasize the moisturizing and antioxidant potential of the moringa-formulation as a new skin drug delivery system. Departamento de Química Analítica Facultad de Medicina Universidad Autónoma de Nuevo León, Av. Fco. I. Madero y Dr. E. Aguirre Pequeño s/n Departamento de Química Analítica Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León, Av. Pedro de Alba s/n Instituto de Biotecnología. Universidad del Papaloapan, Av. Circuito Central No. 200 Col. Parque Industrial. Tuxtepec Instituto de Biociências – Câmpus do litoral Paulista UNESP – Universidade Estadual Paulista, Praça Dom Infante Henrique s/n, Parque Bitaru CEP 11330-900, São Vicente Cátedras CONACYT-UANL Cátedras CONACYT-UNPA Instituto de Biociências – Câmpus do litoral Paulista UNESP – Universidade Estadual Paulista, Praça Dom Infante Henrique s/n, Parque Bitaru CEP 11330-900, São Vicente Consejo Nacional de Ciencia y Tecnología: - Consejo Nacional de Ciencia y Tecnología: 284813 Consejo Nacional de Ciencia y Tecnología: CB/2016

Made available in DSpace on 2020-12-12T01:46:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão Fridericia platyphylla (Cham.) L.G. Lohmann (FP) has cytotoxic, anti-inflammatory, and analgesic properties. We aimed to characterize the cytotoxic and antiproliferative effects of FP extract on normal (GAS) and tumor-derived (ACP02 and HepG2) cell lines. The effective concentrations (EC50s) by tetrazolium bromide assay (MTT) were 56.16, 43.68, and 42.57 µg mL−1 and 69.38, 41.73, and 52.39 µg mL−1 by neutral red assay for GAS, ACP02, and HepG2 cells, respectively. The extract decreased nuclear division indices, which was not reflected in cell proliferation curves. Flow cytometric analyses showed that even 30 µg mL−1 extract (shown to be noncytotoxic by MTT assay) increased the sub-G1 population, indicating cell death due to apoptosis and necrosis. A cytokinesis-block micronucleus cytome assay showed that 30 µg mL−1 of the extract increased the frequency of nuclear buds in tumor cells. Real-time quantitative polymerase chain reaction showed CCND1 upregulation in doxorubicin-treated GAS cells and BCL-XL, BIRC5, and MET downregulation in 5 or 30 µg mL−1 in FP extract-treated ACP02 cells. In conclusion, FP extract modulated apoptosis- and cell cycle-related genes and presented selective cytotoxicity toward tumor cells that deserves further investigation by testing other cell types. Our results demonstrated that even medicinal plants exert adverse effects depending on the extract concentrations used and tissues investigated. Laboratory of Mutagenesis Department of Biological Sciences Faculty of Pharmaceutical Sciences São Paulo State University (UNESP) Laboratory of Mutagenesis and Oncogenetics Department of General Biology Center of Biological Sciences State University of Londrina (UEL) Laboratory of Cytogenetics and Mutagenesis Department of Biology Faculty of Philosophy Sciences and Letters of Ribeirão Preto (FFCLRP) Laboratory of Advanced Studies in Phytomedicines Department of Chemistry Federal University of Maranhão (UFMA) Campus Litoral Paulista São Paulo State University (UNESP) Laboratory of Mutagenesis Department of Biological Sciences Faculty of Pharmaceutical Sciences São Paulo State University (UNESP) Campus Litoral Paulista São Paulo State University (UNESP) Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão: 00863/16

Ageratina havanensis (Kunth) R. M. King &amp, H. Robinson is a species of flowering shrub in the family Asteraceae, native to the Caribbean and Texas. The aim of this work was to compare the quantitative chemical composition of extracts obtained from Ageratina havanensis in its flowering and vegetative stages with the antioxidant potential and to determine the effects on P-glycoprotein (P-gp) function. The quantitative chemical composition of the extracts was determined quantifying their major flavonoids by UPLC-ESI-MS/MS and by PCA analysis. The effects of the extracts on P-gp activity was evaluated by Rhodamine 123 assay, antioxidant properties were determined by DPPH, FRAP and inhibition of lipid peroxidation methods. The obtained results show that major flavonoids were present in higher concentrations in vegetative stage than flowering stage. In particular, the extracts obtained in the flowering season showed a significantly higher ability to sequester free radicals compared to those of the vegetative season, meanwhile, the extracts obtained during the vegetative stage showed a significant inhibitory effect against brain lipid peroxidation and a strong reductive capacity. This study also showed the inhibitory effects of all ethanolic extracts on P-gp function in 4T1 cell line, these effects were unrelated to the phenological stage. This work shows, therefore, the first evidence on: the inhibition of P-gp function, the antioxidant effects and the content of major flavonoids of Ageratina havanensis. According to the obtained results, the species Ageratina havanensis (Kunth) R. M. King &amp, H. Robinson could be a source of new potential inhibitors of drug efflux mediated by P-gp. A special focus on all these aspects must be taking into account for future studies.

Made available in DSpace on 2020-12-12T02:13:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Abstract: Since the beginning, natural products have represented an important source of bioactive molecules for cancer treatment. Among them, cardenolides attract the attention of different research groups due to their cardiotonic and antitumor activity. The observed biological activity is closely related to their Na+/K+-ATPase inhibition potency. Currently, the discovery of new compounds against cancer is an urgent need in modern pharmaceutical research. Thus, the aim of this work is to determine the physicochemical properties and substituent effects that module the antiproliferative activity of cardenolides on the human lung cancer cell line A549. We build and curate a library with results obtained from literature; molecular descriptors were calculated in PaDEL software, and SAR/QSAR analysis was performed. The SAR results showed that cardenolides were sensitive to modifications in C and D steroidal ring and required substituent groups with the function of hydrogen bond acceptor at the C3 position. QSAR models to doubly linked-type cardenolides indicated that properties as lipoaffinity and atoms with the capacity to be hydrogen bond acceptors are involved in the increment of antiproliferative activity on A549 cell line. In contrast, the presence and position of very electro-negative atoms on the molecule decreased the antiproliferative effect on A549 cells. These results suggest that the antiproliferative capacity of cardenolides on the cell line A549 is strongly related to substituent groups on the C3 position, which must not be carbohydrate. Additionally, the steroidal rings C and D must remain without modifications. Graphic abstract: [Figure not available: see fulltext.]. Programa de Doctorado en Ciencias Químico Biológicas y de la Salud Universidad de Sonora Unidad Regional Centro Departamento de Ciencias Químico Biológicas y de la Salud Universidad de Sonora, Blvd. Encinas y Rosales S/N Centro de Investigación de Alimentos y Desarrollo A. C UNESP São Paolo State University, Coastal Campus of São Vicente Escuela de Ciencias de la Salud Universidad Autonoma de Baja California, Blvd. Zartuche y Blvd. Los Lagos, Fraccionamiento Valle Dorado UNESP São Paolo State University, Coastal Campus of São Vicente

Made available in DSpace on 2019-10-06T16:43:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Abstract: We recognize the chemical composition of the acetonic extract of Rhizophora mangle barks (AERM) using mass spectrometry analysis [liquid chromatography (LC)–ESI–IT-MS/MS and matrix-assisted laser desorption/ionization-time of flight-MS (MALDI-TOF)]. Analgesic activity was evaluated by formalin and tail-flick experimental assays. Anti-inflammatory activity was performed by paw edema test induced by carrageenan and 48/80 compounds. The first series of experiments involved [LC]–FIA–IT-MS/MS with 11 separated catechins derivatives until degree of polymerization 3 (DP3). The spectra obtained by MALDI-TOF analysis of the AERM presented two homologous series: one based on polymers of m/z 288 Da increments (up to DP12) and another series based on polymers of m/z [288 + 162] Da increments (up to DP11). In addition to these series of flavan-3-ol, each DP had a subset of masses with a variation of − 16 Da (homologous series of afzelechins—m/z 873–3465 Da) and + 16 Da (homologous series of gallocatechins—m/z 905–3497 Da). A similar pattern with homologous series of gallocatechins and afzelechins could also be observed for a fifth and a sixth monohexoside series: glucogallocatechins (m/z 779–3371) and glucoafzelechins (m/z 747–3339). The intraperitoneal administration of different doses of AERM (50, 150 and 300 µg mL−1) have a morphine-like effect and intense anti-inflammatory activity. Graphical Abstract: [Figure not available: see fulltext.]. Laboratory of Bioprospection of Natural Products (LBPN) UNESP - São Paulo State University/Coastal Campus of São Vicente, Pça Infante Dom Henrique S/N Laboratório de Estudos Avançados em Fitomedicamentos (LEAF) UFMA - Federal University of Maranhão, Av. dos Portugueses, 1966 - Bacanga Embrapa Agroenergy Brazilian Agricultural Research Corporation, W3 Norte, PqEB Laboratory of Bioprospection of Natural Products (LBPN) UNESP - São Paulo State University/Coastal Campus of São Vicente, Pça Infante Dom Henrique S/N FAPESP: 2009/52237-9 FAPESP: 2014/23951-3

Made available in DSpace on 2019-10-06T16:01:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-14 AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing. METHODS In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity. RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed. CONCLUSION In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration. Department of Physiology Institute of Biosciences São Paulo State University (UNESP) Laboratory of Bioactive Compounds São Francisco University Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Programa de Pós-graduação em Ciências Farmacêuticas Núcleo de Investigações Químico-Farmacêuticas (NIQFAR) Universidade do Vale do Itajaí - UNIVALI Coastal Campus of São Vicente São Paulo State University (UNESP), 11330-900 Department of Biological Science Faculty of Sciences and Languages São Paulo State University (UNESP) Department of Physiology Institute of Biosciences São Paulo State University (UNESP) Department of Morphology Institute of Biosciences São Paulo State University (UNESP) Coastal Campus of São Vicente São Paulo State University (UNESP), 11330-900 Department of Biological Science Faculty of Sciences and Languages São Paulo State University (UNESP)

Studies have suggested that a diet rich in functional foods containing flavonoids provides benefits to human health for anti-inflammatory, antioxidant, antibacterial, and anticancer activities. These compounds are usually present in fruits, vegetables and beverages. Human Serum Albumin (HSA) is a predominant carrier protein in blood plasma. The exceptional capacity of HSA to interact with many molecules makes this protein an important regulator of intercellular fluxes. In this work, HSA was used as a model for the study of nanocarrier-flavonoid interaction. The flavonoids investigated were Rutin (RU) and Guaijaverin (GUA). For analytical studies a combination of steady-state fluorescence spectroscopy and molecular modelling calculations were employed. The fluorescence quenching results indicated that the flavonoids binding near residue Trp214, which is localized in the subdomain IIA of HSA. The quenching mechanism is static which indicates the formation of the HSA-flavonoid complexes. The Gibbs free energy changes of both complexes were negative which characterize spontaneous reactions. The molecular modelling results for binding of RU and GUA with HSA are in accordance with the fluorescence spectroscopy data.

Rationale Actinocephalus divaricatus (Eriocaulaceae) is an important source of income for rural communities as it is sold as an ornamental plant. To date, no investigation has been conducted concerning the chemical composition and biological studies of the aerial parts of A. divaricatus. Methods The methanolic extract of the aerial parts of this species was chemically characterized. We applied an analytical dereplication approach based on Liquid Chromatography coupled to High-Resolution Orbitrap Mass Spectrometry in order to develop, identify and define rapidly the metabolite fingerprint of the aerial parts of A. divaricatus. Biological in vitro antitumor tests were undertaken using breast and lung cell lines of mice and humans. Results High-Resolution Mass Spectrometry (HRMS) allowed the fast determination of 30 compounds, which comprised three different classes of compounds: naphthopyranones, flavonoids and saponins. Chromatographic fractionation of the crude methanolic extract validated these results, since it led to the isolation of compounds belonging to the aforementioned classes of compounds, including new acyl glycosylated flavonoids (6-hydroxy-7-methoxyquercetin-3-O-(2"-O-acetyl)-β-D-glucopyranoside and 6-hydroxy-7-methoxyquercetin-3-O-(6"-O-acetyl)-β-D-glucopyranoside), which were fully characterized by Nuclear Magnetic Resonance and Mass Spectrometry experiments, and a known triterpenic saponin (3-O-β-D-glucuronopyranosyl-30-norolean-12,20(29)-dien-28-O-β-D-glucopyranosyl ester). Biological assays indicated that the methanolic extract of the capitula exhibited the best in vitro cytotoxicity against MCF7 cells (human breast cancer). Conclusions The HRMS technique enabled us to identify several classes of compounds. In addition, saponins were identified for the first time in plants belonging to the Eriocaulaceae family. Thus, the essential contribution of this work lies in the new elements it brings to the taxonomic discussion which the Actinocephalus genus as a distinct genus of the Paepalanthus. The results obtained show that the methanolic extract of the capitula could be a promising source of bioactive fractions and/or compounds that may contribute towards breast cancer treatment.

Made available in DSpace on 2018-12-11T17:05:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-12-04 Consejo Nacional de Ciencia y Tecnología Ethnopharmacological relevance Asclepias subulata Decne. (Apocynaceae) is a shrub occurring in Sonora-Arizona desert. The ethnic groups of Sonora, Mexico, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. Aim of the study To determine the cell death pathways that the cardenolide glycosides with antiproliferative activity found in the methanol extract of A. subulata are able to activate. Materials and methods The effect of cardenolide glycosides isolated of A. subulata on induction of apoptosis in cancer cells was evaluated through the measuring of several key events of apoptosis. A549 cells were treated for 12 h with doses of 3.0, 0.2, 3.0 and 1.0 µM of 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively. Apoptotic and necrotic cell levels were measured by double staining with annexin V-FITC/PI. Mitochondrial membrane depolarization was examined through JC-1 staining. Apoptosis cell death and the apoptosis pathways activated by cardenolide glycosides isolated of A. subulata were further characterized by the measurement of caspase-3, caspase-8 and caspase-9 activity. Results Apoptotic assays showed that the four cardenolide glycosides isolated of A. subulata induced apoptosis in A549 cells, which was evidencing by phosphatidylserine externalization in 18.2%, 17.0%, 23.9% and 22.0% for 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, respectively, compared with 4.6% of control cells. Cell death was also associated with a decrease in mitochondrial membrane potential, which was more than 75% in the treated cultures respect to control. The activation of caspase-3 was observed in all cardenolide glycosides-treated cancer cells indicating the caspase-dependent apoptosis of A549 cells. Extrinsic and intrinsic apoptosis pathways were activated by cardenolide glycosides treatment at the doses tested. Conclusion In this study was found that cardenolide glycosides, 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, isolated from A. subulata induced the cell death trough caspase-dependent apoptosis, which was activated, preferably, by extrinsic pathway. Departamento de Investigaciones Científicas y Tecnológicas de la Universidad de Sonora División de Ciencias Biológicas y de la Salud Universidad de Sonora, Blvd. Colosio s/n, entre Sahuaripa y Reforma Colonia Centro Departamento de Ciencias Químico Biológicas División de Ciencias Biológicas y de la Salud Universidad de Sonora, Encinas y Rosales Hermosillo UNESP - São Paulo State University – Institute of Biosciences, Coastal Campus of São Vicente UNESP - São Paulo State University – Institute of Biosciences, Coastal Campus of São Vicente Consejo Nacional de Ciencia y Tecnología: 83462

Made available in DSpace on 2019-10-04T12:38:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Some literature studies have shown the popular use of species of Eugenia sp. leaves as an antioxidant, hypoglycemic, hypotensive and antipyretic. However, the species E. florida DC. shows few studies in this field of knowledge. In this way, it becomes a choice for further research. Several chemical compounds, such as phenolic acids, flavonoids, saponins and tannins, have previously been identified in the species and may be related to biological activity. The aim of present work was done to identify the chemical compounds present in the hydroethanolic extract of Eugenia florida DC. leaves by high-performance liquid chromatography coupled to mass spectrometry, as well as to investigate the antioxidant and antidiabetic effects in alloxan-induced type 1 diabetic rats. Initially, the data collection, specimen deposition of leaves of E. florida DC. and the preparation of the hydroethanolic extract were done. The chemical characterization of the major compounds in the extract was done using a liquid chromatograph coupled to the mass spectrometer, in the negative ionization mode. The evaluation of the antioxidant activity of the extracts was done by the DPPH method. To evaluate the biochemical parameters in the Wistar diabetic rats, alloxan was administered at a dose of 140 mg/kg to the diabetic groups, and the extract was diluted in water to 200 mg/mL and administered to all groups for 30 days. After this period, whole blood from the animals was collected for the determination of some biochemical parameters, as well as livers and kidneys for the evaluation of the effects of the extract on the control of lipid peroxidation. The phytochemical analysis of the extract revealed the presence of substances belonging to the classes described in the literature for the genus Eugenia sp., such as flavonoids, tannins and phenolic acids, based on the molecular mass and the fragmentation patterns obtained. The leaf extract presented potential DPPH radical scavenging activity very close to the catechin standard. In the evaluation of the biochemical parameters of diabetic rats treated with the extract, significant decreases in serum levels of glucose, fructosamine and triglycerides (38.0%, 31.0% and 19.7%, respectively) were observed, as well as an increase in HDL cholesterol (10.3%). The administration of the extract had no significant effect on renal function, AST and ALT activity and on the other parameters of the lipid profile. In addition, there was improvement in liver and kidney damage in treated diabetic animals, through reduction of MDA values in livers and kidneys (17.3% and 13.8%, respectively). Thus, the species E. florida DC. presents an interesting biological potential, due mainly to its bioactive secondary metabolites, which showed promising antioxidant activity and biochemical parameters in diabetic rat models. (C) 2019 SAAB. Published by Elsevier B.V. All rights reserved. Univ Fed Alfenas, Fac Pharmaceut Sci, Dept Foods & Drugs, Alfenas, MG, Brazil Univ Fed Alfenas, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Alfenas, MG, Brazil Univ Fed Maranhao, Dept Chem, Sao Luis, MA, Brazil Sao Paulo State Univ, Inst Biosci, Sao Vicente, SP, Brazil Sao Paulo State Univ, Inst Biosci, Sao Vicente, SP, Brazil CAPES: 001

Three new benzaldehyde derivatives, sporulosaldeins A – C (1–3), and 3 new benzopyran derivatives, sporulosaldeins D – F (4–6), were discovered from an endophytic fungus, Paraphaeosphaeria sp. F03, which was isolated from Paepalanthus planifolius leaves. Compounds 1–6 were elucidated by 1- and 2-dimensional nuclear magnetic resonance experiments and high-resolution mass spectrometry analysis. The absolute configuration of compound 5 was determined through the comparison of experimental and calculated electronic circular dichroism data. Compounds 1–6 were found to exhibit antifungal activity with minimum inhibitory concentration (MIC) values of 7.8 – 250 µg/mL and racemic mixture of compound 6 exhibited weak cytotoxicity against MCF-7 and LM3 with IC50 values of 34.4 and 39.2 µM, respectively.

Made available in DSpace on 2019-10-06T16:56:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 According to the most recent World Health Organization statistics, malaria infected approximately 219 million people in 2017, with an estimate of 435,000 deaths (World Health Organization, 2018). Communities isolated from cities are the most deprived of access to the necessary hospital facilities. Herein we report the development of a transdermal bioadhesive containing artemether (ART), an alternative, potentially lifesaving, treatment regimen for malaria in low-resource settings. Bioadhesives were prepared from an aqueous blend of hydroxyethylcellulose (4.5% w/w), ART, propoxylated-ethoxylated-cetyl-alcohol, polysorbate 80, propyleneglycol, glycerine, mineral oil, and oleic acid. In this study, the average pore size of bioadhesive 5.5b was 52.6 ± 15.31 μm. Differential scanning calorimetry and thermogravimetric analyses confirm the thermal stability of ART bioadhesives at room temperature. Tensile tests indicated good mechanical properties for bioadhesive 5.5b, when compared to 5.5a, where 5.5b showed elastic modulus 0.19 MPa, elongation at break 204%, tensile stress 0.31 MPa, tensile strength at break 0.23 MPa. Bioadhesion assays suggested that formulations containing surfactants had higher detachment forces. Permeation studies demonstrated that the best outcome was achieved with a bioadhesive containing 25 mg ART (5.5b) that after 24 h released 6971 ± 125 μg, which represents approximately 28% of drug permeation. Data reported presents a promising candidate for a new antimalarial transdermal formulation. Graduate School of Bioscience and Technology of Bioactive Products Biology Institute University of Campinas School of Pharmacy Queen's University Belfast Centro Pluridisciplinar de Pesquisas Químicas Biológicas e Agrícolas Departamento de Botânica Instituto de Biociências Universidade de São Paulo UNESP-Univ Estadual Paulista Faculdade de Ciências Farmacêuticas School of Mechanical Engineering University of Campinas University of Calabar UNESP-Univ Estadual Paulista Instituto de Biociências Faculty of Pharmaceutical Science University at Campinas UNESP-Univ Estadual Paulista Faculdade de Ciências Farmacêuticas UNESP-Univ Estadual Paulista Instituto de Biociências

Made available in DSpace on 2020-12-10T19:40:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2021-07-15T15:06:44Z : No. of bitstreams: 1 S1516-89132019000100412.pdf: 585705 bytes, checksum: 3a2d47e9df2f97ad2af651f38c9af498 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Unochapeco Natural products, especially phytochemicals, have been extensively studies and have exhibited important antiproliferative effects. The American native species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is widely distributed in Brazil, where it is known as urtiga-vermelha or urtigao. The leaves are popularly used as anti-inflammatory, antirheumatic and in the treatment of gastric disorders. However, the antiproliferative potential of this plant against human tumor cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of U. baccifera leaves extracts and fractions against a panel of human tumor cell lines in vitro besides a chemical evaluation of the most active sample by mass spectrometry (ESI-IT-MSn). The hydroalcoholic extract was inactive while dichloromethane extract showed moderate cytostatic activity against ovarian carcinoma cell line (OVCAR-3, GI(50) = 1.5 mu g/mL). More, the ethyl acetate and n-butanol fractions did not show important activity against tumour cell while the dichloromethane and hexane fractions showed moderate cytostatic activity against ovarian tumor cell line (OVCAR-3, GI(50) = 12.7 and 9.4 mu g/mL, respectively). Finally, the chemical profile evaluated by mass spectrometry (ESI-IT-MSn) allowed the detection of flavonoids in the HEU and hydroxylated fatty acid in DEU that can explain partially the biological effects observed. This is the first report of the antiproliferative effects of U. baccifera, and DEU has shown potential as a promising source of bioactive compounds. Community Univ Reg Chapeco, Hlth Sci Postgrad Program, Chapeco, SC, Brazil Community Univ Reg Chapeco, Lab Pharmacognosy, Chapeco, SC, Brazil Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP, Brazil State Univ Sao Paulo Juilo de Mesquita Filho, Inst Biosci, Sao Vicente, SP, Brazil State Univ Sao Paulo Juilo de Mesquita Filho, Inst Biosci, Sao Vicente, SP, Brazil

Made available in DSpace on 2018-12-11T17:22:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-05 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de Mato Grosso Ethnopharmacological relevance: Terminalia argentea Mart. (Combretaceae), known mainly as “capitão” is a native tree, not endemic, that occurs in the Amazon, Caatinga, Cerrado and Atlantic Forest in Brazil. Leaf infusion is popularly mentioned by riverine communities that inhabit the microregion of Northern Araguaia (Mato Grosso, Brazil) for the treatment of gastric ulcer, bronchitis and haemorrhage. Considering the wide medicinal use, lack of studies that evaluate the safety of use and the scarcity of phytochemical studies of T. argentea leaves, this work was carried out with the objective of evaluating the toxicity of the hydroethanolic extract of the leaves of T. argentea Mart. (HETa) in experimental models in vivo and in vitro, as well as to advance the phytochemical analysis of HETa. Materials and methods: HETa was prepared by macerating the leaf powder in hydroethanolic solution. Phytochemical characterisation was carried out by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and mass spectrometry through direct flow infusion coupled with electrospray ionization and ion-trap analyzer (DFI-ESI-IT-MS analyses) The contents of phenols, flavonoids and phytosterols were analysed by colorimetric methods. Cytotoxicity was assessed by the Alamar blue assay on Chinese hamster ovary epithelial cells (CHO-K1) and human gastric adenocarcinoma cells (AGS). In vitro genotoxicity of HETa (10, 30 or 100 μg/mL) was assessed by micronucleus (MN) and comet tests using CHO-K1 cells. The acute toxicity assessment was performed by oral administration of HETa in single dose Swiss mice (males and females) up to 2000 mg/kg and sub-chronic toxicity by daily oral administration of HETa (50, 200 and 800 mg/kg) in Wistar rats for 30 days. The parameters related to the clinical and toxicological observations were determined every 6 days and at the end of the treatment the blood was collected for biochemical and haematological analysis, and some organs were removed for macroscopic and histopathological analysis. Results: Preliminary phytochemistry and TLC analysis of HETa revealed the presence of phenolic compounds (18.8%), flavonoids (10.8%), saponins, tannins and phytosterols (19%). The HPLC data revealed the presence of gallic acid, rutin, ellagic acid, catechin, quercetin and kaempferol. In the analysis by DFI-ESI-IT-MS, the presence of gallic acid, rutin, ellagic acid and quercetin was confirmed and identified caffeic acid, quinic acid, galloylmucic acid, quercetin xyloside, quercetin rhamnoside, quercetin glucoside, caffeoyl ellagic acid, quercetin galloyl xyloside, terminalin, quercetin galloyl glucose, corilagin, quercetin digalloyl xyloside, quercetin digalloyl glucoside, punicalin and punicalagin. HETa showed no cytotoxic effect on CHO-K1 and AGS cells. In the MN assay, HETa increased the number of MNs and nuclear buds (NBUDs) in binucleate cells at the three concentrations tested and the nucleoplasmic bridges (NPBs) number at 30 μg/mL. In the comet test, HETa (10 and 100 μg/mL) alone showed a genotoxic effect on CHO-K1 cells. In pre-treatment, HETa at all concentrations tested prevented DNA damage induced by H2O2. In co-treatment with H2O2, HETa showed genotoxic effects at the three concentrations, and post-treatment DNA damage in exposed CHO-K1 cells to H2O2 was repaired in 22.5% with 10 μg/mL HETa. In the acute toxicity test, the HETa did not cause death in the mice, being verified only by piloerection and reversible in 2 h in males and in 4 days in females. No macroscopic changes were observed in the analysed organs. In the sub-chronic toxicity test, the HETa did not cause death in the rats after 30 days and the few changes were: absolute (103/mm3) and relative (%) values of basophils increased by 477.8% and 423% (p < 0.001), respectively, with 50 mg/kg; reduction in feed intake (23.6%, p < 0.01) only on day 18; total cholesterol concentration (13.1%, p < 0.05) and relative heart weight (13.2% %, p < 0.05) at a dose of 800 mg/kg. These effects were not dose-dependent nor followed by clinical signs and symptoms of intoxication, nor of macroscopic and histopathological changes in the organs of animals treated with HETa. Conclusions: The results demonstrated that HETa had no cytotoxic in vitro effects for CHO-K1 and AGS cells. In in vitro genotoxicity assays, the HETa induced different responses, according to concentration and experimental condition. In the MN test the HETa presented genotoxic potential by increasing the number of MNs, NBUDs and NPBs. In the comet assay, HETa was genotoxic by itself and in the co-treatment protocol with H2O2. In pre-treatment or post-treatment protocols with H2O2, HETa presented an antigenotoxic effect by preventing or repairing, respectively, the genotoxicity induced by H2O2. In the in vivo models, HETa was shown to be relatively safe after acute administration in mice [no-observed-adverse effect level (NOAEL) of 2000 mg/kg] and sub-chronic in rats (NOAEL of 800 mg/kg), confirming the riverine information that it is non-toxic in the dosage used. Phytochemical analysis of HETa revealed the presence of phenolic compounds, flavonoids, saponins, tannins and phytosterols. Among the flavonoids and tannins, we highlight gallic acid, rutin, ellagic acid, quercetin, caffeic acid, quinic acid, corilagin, punicalin and punicalagin. Thus, it can be stated that HETa has a good safety margin for therapeutic use. Área de Farmacologia Departamento de Ciências Básicas em Saúde Faculdade de Medicina Universidade Federal de Mato Grosso (UFMT) UNESP - Universidade Estadual Paulista Instituto de Biociências Laboratório de Bioprospecção de Produtos Naturais câmpus do Litoral Paulista Laboratório de Pesquisa em Produtos Naturais Faculdade de Medicina Universidade Federal de Tocantins (UFT) Laboratório de Histologia Departamento de Ciências Básicas em Saúde Faculdade de Medicina Universidade Federal de Mato Grosso (UFMT) Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso (IFMT) Campus Avançado de Lucas do Rio Verde UNESP - Universidade Estadual Paulista Instituto de Biociências Laboratório de Bioprospecção de Produtos Naturais câmpus do Litoral Paulista CAPES: 100234/2013 Fundação de Amparo à Pesquisa do Estado de Mato Grosso: 157529/2014

Made available in DSpace on 2018-11-26T17:06:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-07-01. Added 1 bitstream(s) on 2021-07-15T14:31:54Z : No. of bitstreams: 1 S0102-695X2016000400427.pdf: 541368 bytes, checksum: 506a3f3bed1b2d0690bc1ecc14a4ca73 (MD5) Operculina macrocarpa (L.) Urb., Convolvulaceae, is used by the population as a laxative. In this work we described the isolation of the three phenolic acids present in the hydroethanolic extract of the O. macrocarpa roots. The quantification of the caffeic, chlorogenic acids and of the new caffeic dimer in the hydroethanolic and infusion extracts was performed by high-performance liquid chromatography coupled photodiode array detector. These analyses showed the higher content of the chlorogenic, caffeic and the new 3,4'-dehydrodicaffeic acid in hydroethanolic and hydroethanolic extracts without resin in which infusion. The acid found in greater quantity is caffeic acid followed by the 3,4'-dehydrodicaffeic acid. The laxative activity was evaluated by different experimental models of intestinal transit with the hydroethanolic and infusion extracts, and the resin fraction, caffeic, chlorogenic and ferulic acids. The results showed all extracts and compounds tested had significant activity in the experimental model tested. These results obtained are essential for the future development of a pharmaceutical product with safety and efficacy. (C) 2016 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Farmacos & Med, Programa Posgrad Ciencias Farmaceut, Araraquara, SP, Brazil Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Ciencias, Dept Quim, Bauru, SP, Brazil Univ Estadual Paulista, Campus Litorai Paulista, Sao Vicente, SP, Brazil Ctr Univ Herminio Ometto, Fundacao Heiminio Ometto, Araras, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Farmacos & Med, Programa Posgrad Ciencias Farmaceut, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias, Dept Quim, Bauru, SP, Brazil Univ Estadual Paulista, Campus Litorai Paulista, Sao Vicente, SP, Brazil

Made available in DSpace on 2018-12-11T17:03:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-12-01 Brazilian flora biodiversity has been widely investigated to identify effective and safe phytotherapeutic compounds. Among the investigated plant species, the Byrsonima genus exhibits promising biological activities. This study aimed at evaluating the cytotoxicity of B. correifolia, B. verbascifolia, B. fagifolia and B. intermedia extracts using different assays in two cell lines (primary gastric and HepG2 cells). The different extract concentrations effects on cell viability were assayed using the MTT, aquabluer, neutral red and LDH assays. Non-cytotoxic concentrations were selected to generate cell proliferation curves and to assess cell cycle kinetics by flow cytometry. Byrsonima extracts differentially affected cell viability depending on the metabolic cellular state and the biological parameter evaluated. B. fagifolia and B. intermedia extracts exhibited lower cytotoxic effects than B. correifolia and B. verbascifolia in all assays. The results obtained with LDH and flow cytometry assays were more reliable, suggesting that they can be useful in the screening for herbal medicine and to further characterize these extracts as phytotherapeutic compounds. Department of General Biology State University of Londrina, PR 445 Km 380, s/n - Campus Universitário Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University “Júlio de Mesquita Filho” School of Arts Science and Humanities São Paulo University Institute of Biosciences UNESP- Paulista State University, Coastal Campus of São Vicente Instituto de Investigaciones Biológicas Clemente Estable Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University “Júlio de Mesquita Filho” Institute of Biosciences UNESP- Paulista State University, Coastal Campus of São Vicente

Made available in DSpace on 2020-12-11T19:25:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-15 University of Sonora Bursera microphylla is an endemic plant from Sonora desert, used in folk medicine, however, there is a few scientific information about compounds profile and antioxidant activity. The objective of the study was to determine the phenolic profile and antioxidant activity of B. mycrophylla leaves (BMLE) and fruits (BMFE) extracts. Phenolic content was quantified by the Folin-Ciocalteu assay and phenolic compounds (PC) profile was investigated using UHPLC-ESI-IT-MS and ESI-IT-MSn analysis. Antioxidant activity was evaluated through the 1,1diphenyl-2-picrylhydrazyl (DPPH), trolox equivalent antioxidant capacity (TEAC), oxygen radical antioxidant capacity (ORAC) and ferric reducing antioxidant power (FRAP) methods. Obtained results showed that BMLE (243.4 mg GAE/g) presented higher amount (p < 0.05) of PC compared with BMFE (104.3 mg GAE/g). A total of 11 phenolic compounds were identified in the evaluated extracts (4 phenolic acids, 6 flavonols and 1 flavan-3ol). Antioxidant evaluation results evidenced that BMLE [DPPH IC50 (concentration to inhibit the 50% of DPPH radical): 34.7 mu g/mL; TEAC: 79.3 mu M TE/g; ORAC: 1632.8 mu M TE/g; FRAP: 3809.4 mu M Fe(II)/g] exhibited the greatest capacity (p < 0.05) to stabilize free radicals and reduce metals. Additionally, a strong correlation between antioxidant activity and PC (DPPH vs PC: r= 0.96; TEAC vs PC: r= 0.95; ORAC vs PC: r= 0.96; FRAP vs PC: r= 0.96) was observed. This study is the first one that report the antioxidant potential and phenolic profile of B. mycrophylla plant. In addition, B. mycrophylla extracts showed an interesting antioxidant potential, which could be considered as a natural source of antioxidant compounds. Univ Estadual Paulista, Fac Ciencias Farmaceut, Campus Araraquara,Rodovia Araraquara Jau,Km 01, BR-1480090 Araraquara, SP, Brazil Univ Sonora, Unidad Reg Ctr, Lab Invest Prod Nat, Blvd Luis Donaldo Colosio & Rosales S-N, Hermosillo 83000, Sonora, Mexico Ctr Invest Alimentac & Desarrollo AC, Hermosillo 83304, Sonora, Mexico Univ Sonora, Unidad Reg Norte, Ave K S-N, Eleazar Ortiz Caborca 83600, Sonora, Mexico Univ Estadual Paulista, Fac Ciencias Farmaceut, Campus Araraquara,Rodovia Araraquara Jau,Km 01, BR-1480090 Araraquara, SP, Brazil University of Sonora: USO413005342

Solanum paniculatum L. is widely used in Brazilian folk medicine for the treatment of liver and gastrointestinal disorders as well as for culinary purposes and beverage production. Fractionation of hydroalcoholic [ethanol (EtOH) 70%] tincture from S. paniculatum leaves led to the isolation of six new spirostanic saponins which included 6- O-α-l-rhamnopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,23 R,25 S)-3β,6α,23-trihydroxy-5α-spirostane (1), 6- O-β-d-xylopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,23 R,25 R)-3β,6α,23-trihydroxy-5α-spirostane (4), 3- O-α-l-rhamnopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,23 S,25 R)-3β,6α,23-trihydroxy-5α-spirostane (5), 3- O-β-d-xylopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,23 S,25 R)-3β,6α,23-trihydroxy-5α-spirostane (6), 6- O-α-l-rhamnopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,25 S)-1β,3β,6α-trihydroxy-5α-spirostane (7), and 6- O-β-d-xylopyranosyl-(1''→3')-β-d-quinovopyranosyl-(22 S,25 S)-3β,4β,6α-trihydroxy-5α-spirostane (8) together with two known spirostanic saponins (2, 3). The structures of these compounds were determined by one-dimensional (1D) and two-dimensional (2D) NMR experiments in addition to high-resolution electrospray ionization mass spectrometry (HRESIMS) analyses. The 70% alcohol tincture, used as phytomedicine, exhibited promising activities against oral pathogens, including, Steptococcus sanguinis, St. oralis, St. mutans, St. mitis, and Lactobacillus casei with minimal inhibitory concentration (MIC) values ranging from 6.25 to 50 μg/mL. The saponin fraction, nonetheless, showed lower activity against all the strains tested (from 100 to400 μg/mL).

Made available in DSpace on 2018-12-11T17:18:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 The aim of this study was to evaluate the chemopreventive potential of purple carrot extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). For this purpose, histopathological analysis, proliferative status, antioxidant activity and inflammatory status were investigated in this setting. A total of 20 male rats were distributed into four groups as follows (n = 5 per group): Group 1—free access to water and commercial diet for 12 weeks; Group 2—received 4NQO at 50 ppm dose in drinking water daily and commercial diet for 12 weeks; Group 3—free access to water and received diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks; and Group 4—received 4NQO at 50 ppm dose in drinking water daily and diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks. Histopathological analysis revealed that animals treated with purple carrot extract reduced the oral lesions such as dysplasia and squamous cell carcinoma. Animals with oral pre-neoplastic lesions and treated with purple carrot extract decreased ki-67 and 8-OHdG immunoexpression. Moreover, pNFκBp50 and MyD88 protein expressions were decreased after purple carrot treatment associated or not with 4NQO exposure. SOD-Mn mRNA levels increased with treatment with purple carrot extract as well. In conclusion, our results demonstrated that purple carrot extract was able to protect oral lesions induced by 4NQO in Wistar rats as a result of antioxidant activity, anti-inflammatory potential and antiproliferative and antimutagenic actions. Department of Biosciences Federal University of São Paulo (UNIFESP), Rua Silva Jardim, 136, Vila Mathias Sao Paulo State University (UNESP), Campus Litoral Paulista Sao Paulo State University (UNESP), Campus Litoral Paulista

Seed exudates are plant-derived natural bioactive compounds consisting of a complex mixture of organic and inorganic molecules. Plant seed exudates have been poorly studied against parasite nematodes. This study was undertaken to identify proteins in the Myracrodruon urundeuva seed exudates and to assess the anthelmintic activity against Haemonchus contortus, an important parasite of small ruminants. M. urundeuva seed exudates (SEX) was obtained after immersion of seeds in sodium acetate buffer. SEX was fractionated with ammonium sulfate at 0-90% concentration to generate the ressuspended pellet (SEXF1) and the supernatant (SEXF2). SEX, SEXF1, and SEXF2 were exhaustively dialyzed against distilled water (cut-off: 12 kDa) and the protein contents determined. Mass spectrometry analyses of SEX, SEXF1, and SEXF2 were done to identify proteins and secondary metabolites. The seed exudates contained protease, protease inhibitor, peptidase, chitinase, and lipases as well as the low molecular weight secondary compounds ellagic acid and quercetin rhamnoside. SEX inhibited H. contortus larval development (LDA) (IC50 = 0.29 mg mL-1), but did not affect larval exsheathment (LEIA). On the other hand, although SEXF1 and SEXF2 inhibited H. contortus LEIA (IC50 = 1.04 and 0.93 mg mL-1, respectively), they showed even greater inhibition efficiency of H. contortus larval development (IC50 = 0.29 and 0.42 mg mL-1, respectively). To the best of our knowledge, this study is the first to show the anthelmintic activity of plant exudates against a gastrointestinal nematode. Moreover, it suggests the potential of exuded proteins as candidates to negatively interfere with H. contortus life cycle.

Made available in DSpace on 2018-12-11T17:24:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-05 Plinia cauliflora is a plant species with edible fruits but its chemical composition is not totally known yet although former studies showed its potential as antifungal agent. This work aimed the chemical analysis of the leaves, the activity against fungi species and evaluated cytotoxicity. Extract was obtained with 70% ethanol. An ethyl acetate fraction was obtained and glycosylated quercetin and myricetin were isolated. Samples were tested against Candida species, dermatophytes and entomopathogenic fungi. Cytotoxicity was evaluated against fibroblast cells. Extract showed good activity against C. albicans (minimum inhibitory concentration at 156 μg/mL), C. parapsilosis (78 μg/mL), C. krusei (19 μg/mL), Trichophyton rubrum (78 μg/mL) and Microsporum canis (156 μg/mL). Isolated compounds were more active against C. krusei and T. rubrum. The extract, which was the more active sample, demonstrated low cytotoxic effect and encourage more studies against rising non-albicans species and dermatophyte T. rubrum. Department of Drugs and Medicines, São Paulo State University-UNESP, Araraquara, Brazil Department of Organic Chemistry, São Paulo State University-UNESP, Araraquara, Brazil

Made available in DSpace on 2019-10-06T16:56:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 The analysis by HPLC-PDA of the hydroalcoholic extract of the leaves of M. eriocarpum together with the injection of the fractions containing the already identified metabolites allowed the detection of at least 5 flavonoids, of which two are derived from apigenin and three from luteolin. After isolating larger amounts of isovitexin (I), assays were performed to evaluate the allelopathic activity together with the crude extract. The results show that the initial inhibition indexes were very similar to those observed in the treatments with F17 (Fraction enriched in isovitexin) and F18 (isovitexin), mainly in the concentrations of 500 and 1000 mg L−1. The index of the number of lateral roots, an increase of the inhibitory effect is observed with the increase of the concentration of M. eriocarpum extract. Escola de Artes Ciências e Humanidades USP - Universidade de São Paulo Departamento de Botânica Instituto de Biociências Universidade de São Paulo Campus of São Paulo Coast UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho” Center of Biological and Health Sciences (CCBS) UFMS–Universidade Federal do Mato Grosso do Sul Campo Grande MS Bioscience Institute Botany Department UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho” Departamento de Fisiologia Instituto de Biociências UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho” Campus of São Paulo Coast UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho” Bioscience Institute Botany Department UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho” Departamento de Fisiologia Instituto de Biociências UNESP - Universidade Estadual Paulista “Júlio de Mesquita Filho”

Made available in DSpace on 2018-12-11T17:16:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Bauhinia holophylla (Bong.) Steud. (Fabaceae) is a plant used in Brazilian folk medicine to treat diabetes and inflammation. This study evaluated the phytochemical properties, cytotoxic, apoptotic, mutagenic/antimutagenic effects and alterations in gene expression (RNAm) in HepG2 cells treated with the B. holophylla extract. The phytochemical profile highlight the presence of flavonoids isorhamentin and quercetin derivates. The MTT assay was used to evaluate the cytotoxicity of different concentrations for different treatment times. Three concentrations (7.5, 15, 30 µg/mL) were chosen for assessment of apoptosis (AO/EB), mutagenicity (micronucleus), and cell cycle kinetics (flow cytometry). Thereafter, the concentration of 7.5 µg/mL was chosen to evaluate the protective effects against DNA damage induced by benzo[a]pyrene (B[a]P). At concentrations higher than 7.5 µg/mL (between 10 and 50 µg/mL), the extract was cytotoxic, induced apoptosis, and caused antiproliferative effects. However, it did not induce micronucleus and a reduction of apoptotic and micronucleated cells was observed in treatments that included the extract and B[a]P. The protective effect is attributable to the presence of flavonoids, described as antioxidants, inhibitors of DNA adduct and activators of detoxifying enzymes. The results of the present study such as absence of cytotoxic and mutagenic effects and protective effects against known carcinogens suggest that B. holophylla has potential for use soon as herbal medicine. Department of General Biology Biological Sciences Center State University of Londrina - UEL, Rod Celso Garcia Cid PR 445, Km 380, University Campus, P.O. Box 6001 Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University - UNESP Campus Litoral Paulista São Paulo State University - UNESP Department of Biological Sciences Faculty of Sciences of Bauru São Paulo State University – UNESP Department of Botany Biosciences Institute São Paulo State University - UNESP Institute of Biological Investigation Clemente Estable Department of Biological Sciences Faculty of Pharmaceutical Sciences of Araraquara São Paulo State University - UNESP Campus Litoral Paulista São Paulo State University - UNESP Department of Biological Sciences Faculty of Sciences of Bauru São Paulo State University – UNESP Department of Botany Biosciences Institute São Paulo State University - UNESP FAPESP: 2009/16147-5 FAPESP: 2009/52237-9 FAPESP: 2012/01996-0

Ethnopharmacological relevance Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as “cipo-uva” or “cipo-timbo”. Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. Material and methods We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia–reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE 2 , vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. Results The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro . In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250 mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro , the extract also displayed evident antimicrobial effects against Helicobacter pylori . However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. Conclusions Despite the anti- H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine.

Ethnopharmacological relevance Asclepias subulata Decne. is a shrub occurring in Sonora–Arizona desert (Mexico–USA). The ethnic groups, Seris and Pimas, use this plant for the treatment of sore eyes, gastrointestinal disorders and cancer. Aim of the study To isolate the compounds responsible for antiproliferative activity of the methanol extract of A. subulata. Materials and methods A bioguided fractionation of methanol extract of A. subulata was performed using MTT assay to measure the antiproliferative activity of different compounds on three human cancer cell lines (A549, LS 180 and PC-3), one murine cancer cell line (RAW 264.7) and one human normal cell line (ARPE-19). The methanol extract was partitioned with hexane, ethyl acetate and ethanol. The active fractions, ethanol and residual, were fractioned by silica-column chromatography and active sub-fractions were separated using HPLC. The chemical structures of isolated compounds were elucidated with different chemical and spectroscopic methods. Results A new cardenolide glycoside, 12, 16-dihydroxycalotropin, and three known, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin, were isolated of active sub-fractions. All isolated compounds showed a strong antiproliferative activity in human cancer cells. Calotropin was the more active with IC50 values of 0.0013, 0.06 and 0.41 µM on A549, LS 180 and PC-3 cell lines, respectively; while 12, 16-dihydroxycalotropin reached values of 2.48, 5.62 and 11.70 µM, on the same cells; corotoxigenin 3-O-glucopyranoside had IC50 of 2.64, 3.15 and 6.62 µM and desglucouzarin showed values of 0.90, 6.57 and 6.62, µM. Doxorubicin, positive control, showed IC50 values of 1.78, 6.99 and 3.18 µM, respectively. The isolated compounds had a weak effect on murine cancer cells and human normal cells, exhibiting selectivity to human cancer cells. Conclusion In this study, we found that 12, 16-dihydroxicalotropin, calotropin, corotoxigenin 3-O-glucopyranoside and desglucouzarin are responsible of antiproliferative properties of A. subulata, and that these compounds are highly selective to human cancer cells. Further studies are needed in order to establish the action mechanisms of the isolated compounds.

Acalypha californica Benth., is a plant in the northwestern region from Mexico, commonly known as “cancer herb” and used in traditional medicine for treating cancer. In the present study we have investigated the antiproliferative activity of methanolic extract of A. californica and its fractions in cancer cell lines and phytochemical analysis and mechanism of apoptosis of the fractions with antiproliferative activity. The antiproliferative activity of methanol extract and its fractions of solvents were evaluated by MTT assay against the M12.Ak.C3.F6, RAW 264.7, HeLa and L929 cell lines. Active fractions were fractionated by molecular exclusion chromatography, HPLC and MPLC. The identification of compounds was performed by NMR and FIA-ESI-IT-MS/MS analysis. Apoptotic mechanism was analyzed by flow cytometry, determining the reduction in the mitochondrial membrane potential (JC-1) and the activity of caspases 3, 8 and 9. Cell viability assays showed that the hexane fraction of the methanol extract of the plant has significant effects against cancer lines RAW 264.7 (IC50 = 52.08 ± 1.06 μg/mL) and HeLa (IC50 = 46.77 ± 1.09 μg/mL), the residual fraction showed a selective effect on cell lines M12.Ak.C3.F6 (IC50 = 59.90 ± 1.05 μg/mL), RAW 264.7 (IC50 = 58.93 ± 1.26 μg/mL) and HeLa (IC50 = 50.11 ± 1.135 μg/mL) compared to the control cell line L929 (IC50 = 100.00 ± 1.09 μg/mL). The chemical characterization of the active fractions allowed the identification of β-sitosterol and stigmasterol in hexane fraction and some phenolic acids, proanthocyanidins and flavonoids in the residual fraction. The methanol extract and hexane fraction reduces mitochondrial membrane potential significantly and activates caspases 3, 8 and 9. Because of the antiproliferative activity observed, our results provide a rational basis for the use of extracts of A. californica in treating various types of cancer in traditional medicine from Mexico. The extracts induce apoptosis via activation of caspases.

Made available in DSpace on 2018-11-26T16:16:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-05-01. Added 1 bitstream(s) on 2019-10-09T18:25:36Z : No. of bitstreams: 1 S0102-695X2015000300228.pdf: 675360 bytes, checksum: ed8bbb1454f9719acc059484c6f335cf (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Arrabidaea brachypoda Bureau, Bignoniaceae, known as cipo-una, is widely used in traditional medicine in Southeastern and Northeastern Brazil for kidney stones and painful joints. This study was aimed at evaluating the anti-inflammatory proprieties of the oleanane-type triterpenoid 3 beta-estearioxy-olean-12-ene isolated from the roots of A. brachypoda. Carrageenan-induced paw oedema, formalin test and hot plate test were used to investigate the antiinflammatory activity of 3 beta-estearioxy-olean-12-ene in animals. We observed that 3 beta-estearioxy-olean-12-ene at doses of 5, 10 and 15 mg/kg p.o. demonstrated anti-inflammatory effects, by reduced (p < 0.05) paw oedema induced by carrageenan and by decreased (p < 0.05) licking time caused by a subplantar injection of formalin. In conclusion, 3 beta-estearioxy-olean-12-ene, a triterpene isolated from the roots of A. brachypoda, demonstrate anti-inflammatory effect indifferent tests. Thus, it may be useful in the treatment of inflammatory disorders, which supports previous claims of its traditional use. (C) 2015 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved. Univ Estadual Paulista, Inst Quim, Dept Quim Organ, Araraquara, SP, Brazil Univ Fed Alfenas, Inst Ciencias Biomed, Dept Ciencias Fisiol, Alfenas, MG, Brazil Soc Brasileira Fisiol, Programa Multictr Posgrad Ciencias Fisiol, Sao Paulo, SP, Brazil Univ Fed Vicosa, Dept Quim, Vicosa, MG, Brazil Univ Estadual Paulista, Inst Quim, Dept Quim Organ, Araraquara, SP, Brazil

Made available in DSpace on 2015-10-21T20:58:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-01-01. Added 1 bitstream(s) on 2015-10-22T09:52:42Z : No. of bitstreams: 1 S0102-695X2015000100016.pdf: 1198316 bytes, checksum: 2b987312242bae2e1a5fb1edf85e9f77 (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) PADC-UNESP A large number of quinones have been associated with antitumor, antibacterial, antimalarial, and antifungal activities. Results of previous studies of 5-methoxy-3,4-dehydroxanthomegnin, a naphthoquinone isolated from Paepalanthus latipes Silveira, Eriocaulaceae, revealed antitumor, antibacterial, immunomodulatory, and antioxidant activities. In this study, we assessed the mutagenicity and metabolism-mediated cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin by using the Ames test and a microculture neutral red assay incorporating an S9 fraction (hepatic microsomal fraction and cofactors), respectively. We also evaluated the mutagenic activity in Salmonella typhimurium strains TA100, TA98, TA102, and TA97a, as well as the cytotoxic effect on McCoy cells with and without metabolic activation in both tests. Results indicated that naphthoquinone does not cause mutations by substitution or by addition and deletion of bases in the deoxyribonucleic acid sequence with and without metabolic activation. As previously demonstrated, the in vitro cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin to McCoy cells showed a significant cytotoxic index (CI50) of 11.9 mu g/ml. This index was not altered by addition of the S9 fraction, indicating that the S9 mixture failed to metabolically modify the compound. Our results, allied with more specific biological assays in the future, would contribute to the safe use of 5-methoxy-3,4-dehydroxanthomegnin, compound that has showed in previous studies beneficial properties as a potential anticancer drug. (C) 2014 Sociedade Brasileira de Farmacognosia. Published by Elsevier Editora Ltda. All rights reserved. Univ Fed Espirito Santo, Dept Ciencias Farmaceut, BR-29043900 Vitoria, ES, Brazil Univ Estadual Paulista, Inst Quim Araraquara, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Ciencias Biol, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Anal Clin, Araraquara, SP, Brazil Univ Estadual Paulista, Inst Quim Araraquara, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Ciencias Biol, Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut Araraquara, Dept Anal Clin, Araraquara, SP, Brazil

Made available in DSpace on 2018-11-26T17:39:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-07-25 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations. Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Biol, Celso Garcia Cid Rd,PR 445 Km 380, BR-86057970 Londrina, Parana, Brazil Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil Yale Sch Med, Abraham Ribicoff Res Facil, New Haven, CT USA Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil

Made available in DSpace on 2018-12-11T17:10:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-15 Helminth infections represent a serious problem for the production of small ruminants that is currently aggravated by resistance to anthelmintic products and has induced a search for control alternatives, such as natural products. In this study, extracts of Turnera ulmifolia L. (leaves and roots), Parkia platycephala Benth. (leaves and seeds) and Dimorphandra gardneriana Tul. (leaves and bark), which have been cited in ethnoveterinary studies and selected naturally by goats in the cerrado (Brazilian savanna), were tested in vitro against Haemonchus contortus. Hydroacetonic (ACT) and hydroalcoholic (ETH) extracts were evaluated using an Egg Hatching Assay (EHA), a Larval Exsheathment Inhibition Assay (LEIA) and a Larval Development Assay (LDA). A second set of incubations was performed using polyvinylpolypyrrolidone (PVPP) to determine the influence of polyphenols on the anthelmintic effects of EHA and LEIA. Data from each extract were used to calculate inhibition concentrations (IC50). All tested extracts showed activity against at least one life stage of H. contortus. The use of PVPP revealed that the tannins are not the only extracts of secondary metabolites responsible for the anthelmintic effects. The results showed clear in vitro anthelmintic activities against H. contortus at different stages and indicated the potential use of these species as a promising alternative approach to control helminthic infections of small ruminants. Universidade Federal do Maranhão Centro de Ciências Biológicas e da Saúde Universidade Federal do Maranhão Departamento de Farmácia Universidade Federal do Maranhão Departamento de Química UNESP – Universidade Estadual Paulista Instituto de Biociências Campus do Litoral Paulista UNESP – Universidade Estadual Paulista Instituto de Biociências Campus do Litoral Paulista

Ethnopharmacological relevance An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation. Aim of the study The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents. Material and methods The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP. Results The oral administration of HEEP (125, 250 and 500 mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250 mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l -arginine (500 mg/kg, i.p.) but not by naloxone (1 mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3–30 mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500 mg/kg, p.o.) protected the rats against ethanol (88.4–99.8%) and indomethacin (53–72.3%) and increased the mucus levels of the gastric mucosa without producing an antisecretory effect. The phytochemical profile of HEEP obtained using HPLC-PDA showed secondary metabolites already reported for the genus, mostly flavonoids, gallotannins and proanthocyanidins. Conclusions These data show for the first time that HEEP has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system, the synthesis of nitric oxide and the inhibition of the phosphorylation of p38α MAPK. HEEP also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production. These results support the use of Eugenia punicifolia in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties.

Made available in DSpace on 2015-03-18T15:56:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-10-01Bitstream added on 2015-03-18T16:28:24Z : No. of bitstreams: 1 WOS000344456100039.pdf: 1799519 bytes, checksum: 39aec716d18cec3a02d0c394f0fd13af (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Caesalpinia ferrea Martius has traditionally been used in Brazil for many medicinal purposes, such as the treatment of bronchitis, diabetes and wounds. Despite its use as a medicinal plant, there is still no data regarding the genotoxic effect of the stem bark. This present work aims to assess the qualitative and quantitative profiles of the ethanolic extract from the stem bark of C. ferrea and to evaluate its mutagenic activity, using a Salmonella/microsome assay for this species. As a result, a total of twenty compounds were identified by Flow Injection Analysis Electrospray Ionization Ion Trap Mass Spectrometry (FIA-ESI-IT-MS/MSn) in the ethanolic extract from the stem bark of C. ferrea. Hydrolyzable tannins predominated, principally gallic acid derivatives. The HPLC-DAD method was developed for rapid quantification of six gallic acid compounds and ellagic acid derivatives. C. ferrea is widely used in Brazil, and the absence of any mutagenic effect in the Salmonella/microsome assay is important for pharmacological purposes and the safe use of this plant. Sao Paulo State Univ UNESP, Inst Chem, Dept Organ Chem, BR-14800900 Araraquara, Brazil Mato Grosso Fed Inst IFMT, BR-78043400 Cuiaba, Brazil Mato Grosso Fed Univ UFMT, Inst Nat Human & Social Sci, BR-78557267 Sinop, Brazil Sao Paulo State Univ UNESP, BR-11350000 Sao Vicente, Brazil Sao Paulo State Univ UNESP, Fac Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, Brazil Sao Paulo State Univ UNESP, Inst Chem, Dept Organ Chem, BR-14800900 Araraquara, Brazil Sao Paulo State Univ UNESP, BR-11350000 Sao Vicente, Brazil Sao Paulo State Univ UNESP, Fac Pharmaceut Sci, Dept Biol Sci, BR-14801902 Araraquara, Brazil

Mimosa caesalpiniifolia popularly known as “sabiá” or “sansão-do-campo” is a Brazilian Northeast native perennial tree used for several purposes and in traditional medicine. The aim of the present work was to determine some of the constituents and evaluate the cytotoxic activity of the ethanolic extract of M. caesalpiniifolia leaves (EEM) to MCF-7 cells, a human breast adenocarcinoma cell-line. EEM presented 651.90±6.30mg/g total phenols and 170.11±1.20mg/g flavonoids, namely catechin. EEM and cyclophosphamide (cytotoxic agent) treatment for 24 and 48h decreased the MCF-7 cells protein content, as compared to control cells. Morphological analysis, after hematoxylin–eosin staining of cells, showed changes such as cell rounding-up, shrinkage, nuclear condensation and significantly (p

The antimutagenicity of ten flavonoids, differing in their hydroxylation patterns against direct-acting and indirect-acting mutagens, namely 4-nitro-o-phenylenediamine, sodium azide, mitomycin C, benzo[a]pyrene, aflatoxin B1 and 2-aminofluorene, were compared with the aim of investigating how the hydroxyl groups in their structures govern the biological activity of flavonoids, by the Ames test, with Salmonella typhimurium strains TA98, TA100 and TA102. The flavonoids tested were: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone. In these tests, all compounds were shown to be antimutagenic in more than one strain and various mechanisms of action were demonstrated. The results suggested that the number and position of hydroxyl groups may increase or decrease the protective effect, depending on the type and concentration of flavonoids and mutagen used. These studies contribute to clarifying the mechanisms by which these flavonoids act in protecting DNA from damage. This is required before they can be widely used.

Made available in DSpace on 2015-02-02T12:39:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2014Bitstream added on 2015-02-02T13:07:45Z : No. of bitstreams: 1 S0100-40422014000700003.pdf: 2465139 bytes, checksum: 667337d2851759318201b309af84da89 (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This article describes the isolation and identification of flavonoids in the hydroethanolic extract of the aerial parts from Tonina fluviatilis and evaluation of their antiradical activity. A method based on HPLC-DAD was developed and validated for detecting and quantifying flavonoids in hydroethanolic extracts. The flavonoids identified and quantified in the extract were 6,7-dimethoxyquercetin-3-O-β-D-glucopyranoside (1), 6-hydroxy-7-methoxyquercetin-3-O-β-D-glucopyranoside (2), and 6-methoxyquercetin-3-O-β-D-glucopyranoside (3). The developed method presented good validation parameters, showing that the results obtained are consistent and can be used in ensuring the quantification of these constituents in the extracts. Compounds 2 and 3 showed strong antiradical activity when compared with the positive controls (quercetin and gallic acid). Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica Universidade Estadual Paulista Departamento de Química Universidade Estadual Paulista Universidade Santa Cecília Universidade Federal de Mato Grosso Instituto de Ciências Naturais, Humanas e Sociais Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica Universidade Estadual Paulista Departamento de Química Universidade Estadual Paulista