RESUMEN
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.
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Bignoniaceae/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Neoplasias Gástricas/tratamiento farmacológico , Survivin/metabolismo , Proteína bcl-X/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Necrosis , Extractos Vegetales/química , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Especies Reactivas de Oxígeno , Survivin/genética , Proteína bcl-X/genéticaRESUMEN
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 12h with doses of 3.0, 0.2, 3.0 and 1.0µM 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.
Asunto(s)
Apoptosis/efectos de los fármacos , Asclepias/química , Cardenólidos/farmacología , Glicósidos/farmacología , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Asclepias , Glicósidos/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Glicósidos/aislamiento & purificación , Humanos , Metanol/química , Ratones , Extractos Vegetales/química , Solventes/químicaRESUMEN
Several species of Bauhinia are used in traditional medicine for the treatment of gastrointestinal diseases, diabetes, and inflammation, among other conditions. The aim of this study was to investigate the antiulcer effect of a hydroalcoholic extract from the leaves of B. holophylla. The chemical profile of the extract was determined by HPLC-PAD-ESI-IT-MS. A dose-effect relation was constructed using the ethanol-induced gastric ulcer model in male Wistar rats. Histological analyses and studies of antioxidant and anti-inflammatory activities were performed in stomach samples. The involvement of SH compounds, NO, K(+) ATP channels, and α 2-adrenergic receptors in the gastroprotective effect was evaluated. A toxicity study was performed with a single oral dose of 5000 mg/kg. The extract was composed mainly of cyanoglucoside and flavonol-O-glycosides derivatives of quercetin and myricetin. SH compounds, NO release, K(+) ATP channel activation, and presynaptic α 2-adrenergic receptor stimulation each proved to be involved in the antiulcer effect. The levels of GSH and activity of GR and GPx were increased, and the levels of TNF-α, IL-6 and IL-10 were modulated. There was an antidiarrheal effect and there were no signs of toxicity. B. holophylla presents antiulcer activity mainly by decreasing oxidative stress and attenuating the inflammatory response, without inducing side effects.
RESUMEN
BACKGROUND: Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells. METHODS: Changes induced by nemorosone in the cell cycle and gene expression of the MCF-7 BUS (estrogen-dependent) breast cancer cell line were analyzed using flow cytometry and the RT(2) Profiler PCR array, respectively. RESULTS: In comparison to breast cancer cells without treatment, nemorosone induced discrete cell cycle arrest in the G1 phase and significant depletion in the G2 phase. Moreover, the compound altered the expression of 19 genes related to different pathways, especially the cell cycle, apoptosis and hormone receptors. CONCLUSION: These promising results justify further studies to clarify mechanisms of action of nemorosone, in view of evaluate the possible use of this benzophenone as adjuvant in the treatment of breast cancer.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Benzofenonas/farmacología , Neoplasias de la Mama/patología , Ciclo Celular/efectos de los fármacos , Clusia/química , Femenino , Flores/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7/efectos de los fármacosRESUMEN
O emprego de plantas medicinais refere-se a uma prática milenar, seja na medicina alternativa para cura de diversas doenças, ou como método abortivo. No entanto, a população em geral desconhece os grandes riscos que a cometem. Neste sentido este trabalho teve como objetivo avaliar o índice de consumo de plantas medicinais por mulheres de uma Unidade Básica de Saúde (UBS), na tentativa de identificar quais as espécies mais frequentemente ingeridas inclusive em período gestacional. Através de um questionário de caráter explorativo com 48 mulheres observou-se que a maioria das entrevistadas tinha filhos e as plantas medicinais mais citadas foram "boldo" (Peumus boldus), "carqueja" (Baccharis trimera) e "sene" (Cassia angustifolia), as quais eram empregadas principalmente em dores estomacais ou como digestivos (53%), para resfriados (23%), cólicas menstruais (4%) ou para menstruar (2%). Outra parte do trabalho constituiu a análise visual e química de espécies de plantas medicinais citadas pelo público feminino entrevistado, bem como, outras utilizadas popularmente com propriedades abortivas. Análises visuais comparativas de amostras de plantas medicinais de quatro estabelecimentos comerciais diferentes denominadas Grupo A-C, mostraram a ausência de controle de qualidade com relação às especificações nas embalagens, e separação do material vegetal a ser consumido. Através de análises dos perfis químicos destas amostras por cromatografia em camada delgada (CCD) e cromatografia líquida de alta eficiência (CLAE) indicaram que aquelas pertencentes ao Grupo C diferiram significativamente em relação àquelas de mesma identificação, exceto no que se refere ao boldo do Chile, cujas amostras apresentaram-se bastante similares com relação à constituição química.
The use of medicinal plants corresponds to an ancient practice, either as an alternative medicine for the cure of several diseases, or as a method of abortion. Nevertheless, the population in general does not know the risks involved in the use of medicinal plants. In this sense, the purpose of the study was to evaluate the consumption rate of medicinal plants by women in a Basic Health Unit (BHU), on order to identify which plant species have been most frequently consumed by them, including during the pregnancy. Through an exploratory questionnaire with 48 women, it was observed that most part of the interviewees had children and the most of them cited Peumus boldus, Baccharis trimera and Cassia angustifolia, which were mainly used for stomach aches or digestives (53%), for colds (23%), menstrual cramps (4%) or to menstruate (2%). The remaining part of the study consisted in the visual and chemical analysis of the plant species cited by the interviewees, including other species that have been popularly used as a method of abortion. Comparative visual analysis of medicinal plants (Group A-C) from four different shops showed the absence of quality control concerning packing specifications and the separation of the plant material to be consumed. The analysis of the chemical profiles of these samples by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) indicated that those species belonging to the Group C were significantly different from those plants having the same identification, except for Peumus boldus, whose samples were similar in terms of chemical composition.
Asunto(s)
Adolescente , Adulto , Persona de Mediana Edad , Anciano , Solicitantes de Aborto , Centros de Salud , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Plantas Medicinales/clasificación , Investigación/instrumentaciónRESUMEN
Bioassay-guided fractionation of the chloroform extract of Byrsonima fagifolia leaves led to the isolation of active antitubercular compounds alkane dotriacontane (Minimal Inhibitory Concentration-MIC, 62.5 µg mL(-1)), triterpenoids as bassic acid (MIC = 2.5 µg mL(-1)), α-amyrin acetate (MIC = 62.5 µg mL(-1)), a mixture of lupeol, α- and ß-amyrin (MIC = 31.5 µg mL(-1)) and a mixture of lupeol, and acetates of α- and ß-amyrin (MIC = 31.5 µg mL(-1)). The antimycobacterial activity was determined by the Microplate Alamar Blue Assay (MABA) and the structures of promising compounds were determined by spectroscopic analysis. This investigation constitutes the first report of a chemical and antitubercular study of apolar compounds from B. fagifolia Niedenzu (IK).
RESUMEN
AIM OF THE STUDY: Mouriri pusa, popularly known as "manapuçá" or "jaboticaba do mato", is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects. MATERIALS AND METHODS: The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid. RESULTS: In the acute model, treatment with either, TF (25mg/kg) or FF (50mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers' regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed. CONCLUSIONS: Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety.
Asunto(s)
Antiulcerosos/uso terapéutico , Flavonoides/uso terapéutico , Melastomataceae , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Taninos/uso terapéutico , Animales , Antiulcerosos/aislamiento & purificación , Brasil , Flavonoides/aislamiento & purificación , Masculino , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Ratas , Ratas Wistar , Úlcera Gástrica/patología , Úlcera Gástrica/prevención & control , Taninos/aislamiento & purificación , Resultado del TratamientoRESUMEN
Leaf fractions of Wilbrandia ebracteata were investigated for anti-ulcerogenic effects in ethanol and indomethacin-induced gastric ulcer assays in mice. Protective anti-ulcer effects were detected only in the ethanol-induced ulcer assay effects after pre-treatment with MeOH extract, MeOH chlorophyll-free, chlorophyll residue, HEX, DCM, aqueous MeOH fraction, ethyl acetate (EtOAc) and aqueous fractions. A potent anti-ulcerogenic effect was determined after pre-treatment of animals with EtOAc fraction, which was fractionated for isolation of active constituents. Seven flavonoids, 3',4',5,6,7,8-hexahydroxyflavonol, orientin, isoorientin, vitexin, isovitexin, luteolin, 6-methoxi-luteolin were isolated from the leaves of W. ebracteata (Cucurbitaceae) by chromatographic methods and identified by their spectral data. The data suggest that flavonoids are active anti-ulcerogenic compounds from leaves of W. ebracteata. The ability of scavenging free radicals was evaluated by DPPH reduction assay by TLC of flavonoids isolated.
Asunto(s)
Antiulcerosos/farmacología , Cucurbitaceae/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Plantas Medicinales/química , Administración Oral , Animales , Antiulcerosos/uso terapéutico , Compuestos de Bifenilo , Brasil , Flavonoides/química , Flavonoides/uso terapéutico , Indometacina/farmacología , Ratones , Picratos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoAsunto(s)
Toxicología , Toxicología , Biodiversidad , Venenos , Intoxicación , Toxinas Biológicas , Toxicología , Zoología , BiodiversidadRESUMEN
Among the current treatment strategies for the peptic ulcer patient with Helicobacter pylori infection, the method of choice is triple therapy based on the concurrent use of proton inhibitors and two antibiotics. Alchornea triplinervia is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. In the present work we proposed therapy based on this medicinal plant that presents effective gastroprotective action with antibiotic effects. Oral pretreatment with methanolic extract (ME) of A. triplinervia in rats and mice decreased the gastric injuries induced by ethanol and HCl/ethanol. Increasing the dose reduced the gastroprotective effects of ME on the gastric lesions induced by nonsteroidal anti-inflammatory drug. After pylorus ligature of mice, oral administration of ME induced a decrease not only in total acid but also in the ulcer index. We also observed that ME displayed antibacterial activity against H. pylori. Liquid-liquid separation of ME indicated that active constituents responsible for the gastroprotective action are concentrated in the ethyl acetate fraction (EAF) (50% protection) rather than in the aqueous fraction, which did not induce significant gastroprotection at the same dose (100 mg/kg). EAF induced an increase of gastric mucosa prostaglandin (PG) E(2) levels, which remained high even after previous administration of indomethacin. The phytochemical profile of ME revealed that EAF contains mainly flavonoids. In conclusion, all these results suggest that ME did not show acute toxicity, but exhibited an antisecretory property, anti-H. pylori effect, and gastroprotective action. The observed effect did not involve the participation of nitric oxide or endogenous sulfhydryl groups. However, EAF showed a more efficient gastroprotective effect than ME at a lower dose and protected the gastric mucosa by increasing PGE(2).
Asunto(s)
Antibacterianos/farmacología , Antiulcerosos/farmacología , Euphorbiaceae , Helicobacter pylori/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Úlcera Gástrica/prevención & control , Administración Oral , Animales , Antibacterianos/administración & dosificación , Antiulcerosos/administración & dosificación , Brasil , Relación Dosis-Respuesta a Droga , Femenino , Flavonoides/análisis , Jugo Gástrico/efectos de los fármacos , Mucosa Gástrica/patología , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Masculino , Ratones , Extractos Vegetales/toxicidad , Prostaglandinas/biosíntesis , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamenteRESUMEN
Mouriri pusa Gardner and Mouriri elliptica Martius are fruit-bearing plants of the Melastomataceae family, popularly known in Brazil as puçá-preto or jaboticaba-do-cerrado, and they are used in folk medicine for the treatment of gastric ulcers. In this study, we employ the Ames test to assess the mutagenicity of compounds obtained from the leaves of these species. The methanol extract of the M. pusa was mutagenic to the Salmonella typhimurium strains TA98, TA97a and TA100, with or without metabolic activation. The methanol extract of M. elliptica induced mutagenic activity in TA98 when metabolized with S9 fraction and TA97a with and without S9, but with lower mutagenicity index (MI) and potencies values than those for M. pusa. Enriched fractions of flavonoids and tannins of M. pusa were also evaluated and they demonstrated positive mutagenicity. The highest values of MI and potency were obtained with the flavonoid fraction, which contains large amounts of quercetin, quercetin glycosides and myricetin. These compounds are probably related to the mutagenicity observed in the Ames test. The dichloromethane extract was not mutagenic in any of the test conditions employed.
Asunto(s)
Melastomataceae/toxicidad , Mutágenos/toxicidad , Animales , Cromatografía Líquida de Alta Presión , Flavonoides/toxicidad , Técnicas In Vitro , Pruebas de Mutagenicidad , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Ratas , Salmonella/efectos de los fármacos , Salmonella/genética , Fracciones Subcelulares/efectos de los fármacos , Taninos/toxicidadRESUMEN
In order to determine the potential of Cerrado plants as sources of antimicrobial activity, the phytochemical screening of ethanol extracts from Virola surinamensis, Qualea grandiflora, Alchornea castaneifolia, Hancornia speciosa and Curatella americana traditionally used in folk medicine are reported.
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Antiinfecciosos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Antiinfecciosos/química , Apocynaceae/química , Brasil , Dilleniaceae/química , Lauraceae/química , Magnoliopsida/química , Pruebas de Sensibilidad Microbiana , Myristicaceae/química , Extractos Vegetales/química , Trichosporon/efectos de los fármacosRESUMEN
Several plants are used in folk medicine to treat gastrointestinal disorders. Ananas ananassoides (Baker) L.B. Smith (Family Bromeliaceae) is a medicinal plant commonly used in the central region of Brazil against gastric pain. We evaluated two extracts (methanol [MeOH] and dichloromethane [DCM]) obtained from the leaves of A. ananassoides for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% ethanol, absolute ethanol, non-steroidal anti-inflammatory drugs, and pylorus ligation) in mice and rats. The best results were obtained after pretreatment with the DCM extract, whereas the MeOH extract did not show any significant anti-ulcerogenic activity but presented mutagenic action. The mechanism of action of the DCM extract suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. The data, taken together with the absence of acute toxicity and mutagenicity, indicate the apolar extract, instead of the polar, extract of A. ananassoides as a safe and potential new anti-ulcerogenic drug.
Asunto(s)
Ananas/química , Mutágenos/farmacología , Fitoterapia , Extractos Vegetales/toxicidad , Extractos Vegetales/uso terapéutico , Gastropatías/prevención & control , Animales , Brasil , Etanol , Mucosa Gástrica/efectos de los fármacos , Masculino , Metanol , Cloruro de Metileno , Ratones , Pruebas de Mutagenicidad , Hojas de la Planta/química , Ratas , Ratas Wistar , Gastropatías/inducido químicamente , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & controlRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used by people living in the Cerrado to treat gastrointestinal disturbances. This medicinal plant has shown intense gastroprotective action in rodent gastric lesion, but still there are no data about its healing effect on gastric mucosa. AIM OF THE STUDY: To evaluate the methanolic extract (MeOH) obtained from Mouriri pusa leaves for its effect on the cicatrisation process of gastric ulcer. MATERIALS AND METHODS: The healing effects on gastric ulcers inducted by subserosal injection of acetic acid were evaluated by macroscopic and microscopic measures, immunohistochemistry and cell counting in rats treated with MeOH extract of Mouriri pusa (250 mg/kg, p.o./daily) for 14 or 30 days. The toxicity of Mouriri pusa was also evaluated by body and organ weight measure and clinical biochemical parameters. RESULTS: Mouriri pusa treatments lasting 14 and 30 days showed elevated mucus secretion (PAS) and thicker regenerative gastric mucosa, denoting increased cell proliferation, which was confirmed by PCNA immunohistochemical analysis. Moreover, there was important cell recruitment (neutrophils and mast cells) to the site of the ulcer, which is an important factor in ulcer healing. No toxic effect was observed in all parameters evaluated. Phenolic compounds present in the MeOH extract like tannins, flavonoids and epicatechin are the probable agents involved in the healing effects of this medicinal plant. CONCLUSIONS: These findings showed a potential effect of Mouriri pusa in increasing regeneration of damaged gastric mucosa with safety for human use.
Asunto(s)
Antiulcerosos/farmacología , Melastomataceae/química , Extractos Vegetales/farmacología , Úlcera Gástrica/tratamiento farmacológico , Ácido Acético , Administración Oral , Animales , Antiulcerosos/efectos adversos , Antiulcerosos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Moco/efectos de los fármacos , Moco/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Fenoles/aislamiento & purificación , Fenoles/farmacología , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Factores de TiempoRESUMEN
Strychnos pseudoquina St. Hil. is a native plant of the Brazilian Savannah, used in popular medicine to treat a number of conditions. Since it contains large quantities of alkaloids with proven antiulcer activity, we tested the genotoxic potential of crude extracts and fractions containing alkaloids and flavonoids from the leaves of this plant, on Salmonella typhimurium and performed the micronucleus test on peripheral blood cells of mice treated in vivo. The results showed that the methanol extract of the leaves of S. pseudoquina is mutagenic to the TA98 (-S9) and TA100 (+S9, -S9) strains of Salmonella. The dichloromethane extract was not mutagenic to any of the tested strains. Fractions enriched with alkaloids or flavonoids were not mutagenic. In vivo tests were done on the crude methanol extract in albino Swiss mice, which were treated, by gavage, with three different doses of the extract. The highest dose tested (1800 mg/kgb.w.) induced micronuclei after acute treatment, confirming the mutagenic potential of the methanol extract of the leaves of S. pseudoquina. In high doses, constituents of S. pseudoquina compounds act on DNA, causing breaks and giving rise to micronuclei in the blood cells of treated animals.
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Antiulcerosos/toxicidad , Micronúcleos con Defecto Cromosómico/efectos de los fármacos , Mutágenos/toxicidad , Extractos Vegetales/toxicidad , Salmonella typhimurium/efectos de los fármacos , Strychnos , Administración Oral , Animales , Antiulcerosos/metabolismo , Fraccionamiento Químico , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Metanol/química , Ratones , Pruebas de Micronúcleos , Mutágenos/metabolismo , Extractos Vegetales/metabolismo , Plantas Medicinales/química , Reticulocitos/efectos de los fármacos , Proteína Ribosómica S9 , Proteínas Ribosómicas/efectos de los fármacos , Proteínas Ribosómicas/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Strychnos/químicaRESUMEN
This study was designed to determine the effect of Mangifera indica flowers decoction, on the acute and subacute models of induced ulcer in mice and rats. A single oral administration of the aqueous decoction (AD) from M. indica up to a dose of 5 g/kg, p.o. did not produce any signs or symptom of toxicity in the treated animals. The oral pre-treatment with AD (250, 500 and 1000 mg/kg) in rats with gastric lesions induced by ethanol, decreased the gastric lesions from 89.0+/-6.71 (control group) to 9.25+/-2.75, 4.50+/-3.30 and 0, respectively. Pretreatment with AD (250, 500 and 1000 mg/kg) to mice with HCl/ethanol- or stress-induced gastric lesions resulted in a dose-dependent significant decrease of lesion index. In the piroxicam-induced gastric lesions, the gastroprotective effect of AD was reducing with the increase of the AD dose. In the pylorus-ligature, AD (p.o.) significantly decreased the acid output indicating the antisecretory property involved in the gastroprotective effect of M. indica. Treatment with AD during 14 consecutive days significantly accelerated the healing process in subacute gastric ulcer induced by acetic acid in rats. Pretreatment with N-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO-synthase, did not abolish the gastroprotective effects (99% with saline versus 80% with l-NAME) of AD against ethanol-induced gastric lesions. Pretreatment with N-ethylmaleimide (NEM), a blocker of endogenous sulphydryl group, significantly abolished the protective effects of AD against ethanol-induced gastric ulcers (95% with saline versus 47% with NEM). Phytochemical screening showed the presence of steroids, triterpenes, phenolic compounds and flavonoids. Estimation of the global polyphenol content in the AD was performed by Folin-Ciocalteu method and showed approximately 53% of total phenolic on this extract. These findings indicate the potential gastroprotective and ulcer-healing properties of aqueous decoction of M. indica flowers and further support its popular use in gastrointestinal disorders in Caribbean.
Asunto(s)
Antiulcerosos/uso terapéutico , Flores/química , Mangifera/química , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Estómago/efectos de los fármacos , Animales , Inhibidores de la Ciclooxigenasa/toxicidad , Etanol/toxicidad , Etilmaleimida/toxicidad , Flavonoides/química , Ácido Gástrico/metabolismo , Ácido Clorhídrico/toxicidad , Masculino , Ratones , Fenoles/química , Polifenoles , Ratas , Ratas Wistar , Estómago/patología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patologíaRESUMEN
Qualea grandiflora is one of the species widely used in folk medicine to treat gastric ulcers in Cerrado of the central region of Brazil. The hydroalcoholic extract of bark (HE) of Qualea grandiflora was investigated for their ability to prevent and heal lesions in the gastric mucosa. The oral administration of HE exhibited antiulcer activity decreasing the ulcerative index induced by HCl/ethanol solution, indomethacin/bethanechol and stress. In the Shay model, results showed that HE (p.o.) only reduced the severity of gastric lesions without effects on pH, gastric acidity or volume. When given by intraduodenal route, HE changed the pH, but did not modify the other parameters of the gastric juice. These data were in accordance with those obtained when HE was administered orally for 14 days after gastric ulcers were induced by acetic acid in rats. HE presented healing process in subacute gastric ulcer induced by acetic acid in rats. Moreover, histological examinations showed the simple columnar epithelium, lamina propria with simple branched tubular glandules with dilated lumen and large amounts of mucus secretion. Phytochemical investigation of HE led to the detection of terpenes, steroids, saponins, phenolic compounds and tannins in this extract, which may be involved in the observed activity.