RESUMO
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 µM) or ISA (0.5 to 50 µM). 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 µM) and HeLa cells (10 to 200 µM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 µM; HeLa: 5 and 10 µM). 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.
Assuntos
Dano ao DNA/fisiologia , Proteínas de Ligação a DNA/biossíntese , Endonucleases/biossíntese , Isatina/farmacologia , Mutagênese/fisiologia , Proteína X Associada a bcl-2/biossíntese , Animais , Antibióticos Antineoplásicos/isolamento & purificação , Antibióticos Antineoplásicos/farmacologia , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cricetinae , Cricetulus , Dano ao DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Endonucleases/genética , Feminino , Expressão Gênica , Células HeLa , Humanos , Indóis/isolamento & purificação , Indóis/farmacologia , Isatina/isolamento & purificação , Masculino , Camundongos , Mutagênese/efeitos dos fármacos , Componentes Aéreos da Planta , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Proteína X Associada a bcl-2/genéticaRESUMO
BACKGROUND: Syngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as "sempre-vivas," are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action. METHODS: The activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated. RESULTS: In chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. CONCLUSIONS: The results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.
Assuntos
Antiulcerosos/administração & dosagem , Eriocaulaceae/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Humanos , Masculino , Camundongos , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/metabolismo , Úlcera Gástrica/fisiopatologia , Cicatrização/efeitos dos fármacosRESUMO
Isatin (1H-indole-2,3-dione) is a chemical found in various medicinal plant species and responsible for a broad spectrum of pharmacological and biological properties that may be beneficial to human health, as an anticonvulsant, antibacterial, antifungal, antiviral, and anticancer agent. The aim of the present study was to determine in vitro the cytotoxic, mutagenic, and apoptotic effects of isatin on CHO-K1 and HeLa cells using the MTT viability assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide), micronucleus (MN) test, apoptosis index, and nuclear division index (NDI). The 5 isatin concentrations evaluated in the mutagenicity and apoptosis tests were 0.5, 1, 5, 10, and 50 µM, selected through a preliminary MTT assay. Positive (doxorubicin, DXR) and negative (phosphate buffered saline, PBS) control groups were also included in the analysis. Isatin did not exert a mutagenic effect on CHO-K1 after 3 and 24 h of treatment or on HeLa cells after 24 h. However, 10 and 50 µM concentrations inhibited cell proliferation and promoted apoptosis in both CHO-K1 and HeLa cells. Data indicate that the cytotoxic, apoptotic, and antiproliferative effects of isatin were concentration independent and cell line independent.
Assuntos
Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Isatina/toxicidade , Mutagênicos/toxicidade , Plantas Medicinais/química , Animais , Células CHO , Divisão Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Cricetinae , Cricetulus , DNA de Neoplasias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células HeLa , Humanos , Isatina/classificação , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos/métodos , Mutagênicos/classificação , Extratos Vegetais/classificação , Extratos Vegetais/toxicidade , Sais de Tetrazólio , TiazóisRESUMO
The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE(2) production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes.
Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Indigofera/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Cicatrização/efeitos dos fármacos , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Antioxidantes/administração & dosagem , Antioxidantes/química , Modelos Animais de Doenças , Etanol/efeitos adversos , Suco Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Masculino , Metaboloma , Metabolômica , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Prostaglandinas/biossíntese , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Metabolismo Secundário , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismo , Compostos de Sulfidrila/farmacologia , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera suffruticosa is specie typical of the "Cerrado" or Brazilian savannah; it is a member of the Fabaceae family - in folkmedicine is used for gastric disorders, infection and inflammation. AIM OF THE STUDY: Ethyl acetate fraction (AcF) and aqueous fraction (AqF) of the methanolic extract of I. suffruticosa leaves were evaluated against acute gastric ulcer. The AcF fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. MATERIALS AND METHODS: The gastroprotective action of AcF and AqF fractions were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action, mucus and prostaglandin production, toxicological and healing activity of the AcF (100mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA and HSP-70) assays to evaluate the effects of I. suffruticosa. RESULTS: AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant in 100mg/kg group compared vehicle. AcF did not interfered with gastric secretion, significantly increased the PGE(2) and mucus production (validated in PAS technique). The gastroprotection was attenuated by pretreatment with N-ethylmaleimide, but not L-NAME. In acid-acetic-induced ulcer model AcF accelerated ulcer healing. Immunohistochemistry analysis showed induction of proliferating cell (PCNA) and heat shock protein (HSP 70). CONCLUSIONS: These results showed that AcF acted as gastroprotective agent stimulating prostaglandin, mucus and HSP70.
Assuntos
Antiulcerosos/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Indigofera , Muco/metabolismo , Extratos Vegetais/farmacologia , Prostaglandinas/metabolismo , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Acetatos/química , Animais , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Citoproteção , Modelos Animais de Doenças , Etanol , Mucosa Gástrica/metabolismo , Imuno-Histoquímica , Indigofera/química , Masculino , Metanol/química , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Solventes/química , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Compostos de Sulfidrila/metabolismo , Água/químicaRESUMO
Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo, using the comet assay and the micronucleus test. Three doses (50, 100, and 150mg/kgb.w.) were administered to mice via gavage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1g/kgb.w. To evaluate the results, parametric (ANOVA/Tukey) and non-parametric (Kruskal-Wallis/Dunn's post hoc test) tests were used, according to the nature of the data distribution. At all doses (50, 100 and 150mg/kgb.w.), after acute treatment with isatin, alterations in DNA migration (comet assay) were not observed and mutagenic effects were not seen (micronucleus test on peripheral blood cells). After repeated doses, only the highest dose of isatin (150mg/kgb.w.) induced alterations in the DNA that gave rise to micronuclei in the bone marrow and peripheral blood cells of the mice. Our results show that the mutagenic and genotoxic effects of isatin depend on dose and on period of exposure.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Dano ao DNA , Isatina/farmacologia , Leucócitos/efeitos dos fármacos , Animais , Células da Medula Óssea/metabolismo , Ensaio Cometa , Relação Dose-Resposta a Droga , Feminino , Isatina/administração & dosagem , Isatina/toxicidade , Leucócitos/metabolismo , Masculino , Camundongos , Testes para Micronúcleos , Microscopia de Fluorescência , Testes de Mutagenicidade , Reticulócitos/efeitos dos fármacos , Reticulócitos/metabolismo , Fatores de TempoRESUMO
Indigofera truxillensis and I. suffruticosa, are used as a source of indigo dye and to treat several diseases. The mutagenic activity of the methanolic extracts from aerial parts, glycerolipid, flavonoid and alkaloid fractions of the extract were evaluated by means of Salmonella/microsome assays using TA100, TA98, TA102 and TA97a strains. The methanolic extract of I. truxillensis showed mutagenic activity in the TA98 strain without S9 while glycerolipid fraction was devoid of activity. The flavonoid and alkaloid fractions of both plants showed mutagenicity. Chemical analysis of flavonoid fractions of I. truxillensis and I. suffruticosa resulted in the identification of kaempferol, quercetin and their derivatives. The alkaloid fraction of both the species contained indigo and indirubin and indigo was found mainly responsible for the mutagenic activity.
RESUMO
CONTEXT: Alchornea triplinervia (Spreng.) Müll. Arg. (Euphorbiaceae) is a tree widespread in many Brazilian states. This plant naturally occurs in different ecosystems including tropical Atlantic forest, Amazon rain forest, moist tropical mixed forest, savanna forest, among others. Local populations traditionally use it in tea form to treat gastric disturbances. OBJECTIVE: The objective of this research was to evaluate the plant A. triplinervia as a potential inhibitor of some macrophage functions involved in the inflammatory process. MATERIALS AND METHODS: The effects of Alchornea triplinervia ethyl acetate fraction (AtF) on hydrogen peroxide (H2O2), nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production in peritoneal macrophages were investigated using phenol red, Griess reagent and a sandwich immunoassay, respectively. RESULTS: AtF chromatographic analyses indicate the presence of flavonoids as majority compounds. The fraction also showed an intense inhibition of H2O2 and NO production. The inhibitory effects of the fraction in H2O2 and NO production ranged from 72.25 ± 4.68 to 69.64 ± 4.21 and from 47.8 ± 8.96 to 76.77 ± 8.11%, respectively in the two tested concentrations, 15.62 and 62.5 µg/mL. TNF-α production was partially inhibited in the tested concentrations and the inhibitory rate was around 18%. DISCUSSION AND CONCLUSION: It is supposed that the elevated biological potential of A. triplinervia is related to the presence of phenolic compounds in the plant leaves. According to the results observed in this study, it is suggested that AtF presents anti-inflammatory activity, supporting the traditional use of A. triplinervia in Brazilian folk medicine.
Assuntos
Anti-Inflamatórios/farmacologia , Euphorbiaceae/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Brasil , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Peróxido de Hidrogênio/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Medicina Tradicional , Camundongos , Óxido Nítrico/metabolismo , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/administração & dosagem , Folhas de Planta , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (85%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.
Assuntos
Antiulcerosos/farmacologia , Proliferação de Células/efeitos dos fármacos , Euphorbiaceae/química , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis/toxicidade , Animais , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Atropina/farmacologia , Relação Dose-Resposta a Droga , Suco Gástrico/efeitos dos fármacos , Suco Gástrico/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/fisiopatologia , Trânsito Gastrointestinal/efeitos dos fármacos , Lansoprazol , Masculino , Medicina Tradicional , Metanol , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle , Testes de Toxicidade Aguda , Cicatrização/efeitos dos fármacosRESUMO
The genus Indigofera (Fabaceae) is used in folk medicine to treat gastrointestinal pain. In this study, we investigated the antiulcerogenic properties of Indigofera truxillensis Kunth. Oral administration of MeOH extract did not produce any signals of acute toxicity. The antiulcerogenic activity was assessed in different models of acute gastric ulcers (100 percent ethanol, piroxicam 30 mg.kg-1, hypothermic restraint stress and pylorus ligature) in mice and rats. The animals were treated with the drugs lanzoprazole (30 mg.kg-1) or cimetidine (100 mg.kg-1) as positive controls depending on the performed model. In another experiment with ethanol-induced ulcers in rats, N-ethylmaleimide (NEM), a sulfhydryl group blocker, was also used. The MeOH extract, at doses of 250, 500 and 1000 mg.kg-1, inhibited the gastric lesions in all experiments: a) by 62 percent, 69 percent and 32 percent, respectively, in piroxicam-induced lesions, b) by 43 percent, 71 percent and 98 percent, in ethanol-induced lesions, c) by 69 percent, 64 and 89 percent, in hypothermic-restraint stress-induced lesions, d) by 73 percent, 82 percent and 84 percent, in pylorus ligature lesions. Significant changes in the total gastric acid levels were also found after intraduodenal administration of the MeOH extract in the ligated pylorus model. Pre treatment with NEM reduced partially the antiulcerogenic activity of the MeOH extract in ethanol-induced gastric lesions. This result indicates an increase in the levels of non-protein sulfhydryl groups by MeOH extract in the gastric mucosa. These results indicate that the MeOH extract has antisecretory and citoprotective effects that may be related to the presence of flavonoids detected by phytochemical analysis.
O gênero Indigofera (Fabaceae) é utilizado na medicina tradicional para distúrbios gastrintestinais. Em nosso trabalho foi investigada a propriedade antiulcerogênica da Indigofera truxillensis Kunth. A administração oral do extrato metanólico (MeOH) não produziu efeitos tóxicos. A atividade antiulcerogênica foi avaliada em diferentes modelos agudos de úlcera gástrica (etanol 100 por cento, piroxicam 30 mg.kg-1, estresse por retenção e frio e ligadura do piloro) em camundongos e ratos. Os animais foram tratados com lansoprazol (30 mg.kg-1) ou cimetidina (100 mg.kg-1), que foram utilizados como controle positivo dependendo do modelo testado. Em outro experimento com úlcera induzida por etanol em ratos, N-etilmaleimida (NEM), um bloqueador dos compostos sulfidríla, também foi utilizado. O extrato metanólico, nas doses de 250, 500 e 1000 mg.kg-1, inibiu significativamente as lesões gástricas em todos os experimentos: a) 62 por cento, 69 por cento e 32 por cento, respectivamente, nas lesões gástricas induzidas por piroxicam, b) 43 por cento, 71 por cento e 98 por cento, nas lesões gástricas induzidas por etanol, c) 69 por cento, 64 por cento e 89 por cento, nas lesões gástricas induzidas por estresse por contenção e frio, d) 73 por cento, 82 por cento e 84 por cento, nas lesões gástricas induzidas por ligadura de piloro. Alterações significativas foram observadas na concentração total de ácido gástrico após a administração via intraduodenal do extrato MeOH no modelo de ligadura do piloro. Pré-tratamento com NEM reduziu parcialmente a atividade antiulcerogênica do extrato MeOH na úlcera induzida por etanol, o que sugere um aumento nos níveis de compostos sulfidríla pelo extrato MeOH na mucosa gástrica. Os resultados indicam que o extrato MeOH possui um efeito antisecretor e citoprotetor, e que tais efeitos podem estar relacionados com a presença de flavonóides detectados por análise fitoquímica no extrato MeOH.
Assuntos
Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/toxicidade , Gastroenteropatias/classificação , Gastroenteropatias/complicações , Gastroenteropatias/terapia , RatosRESUMO
The effects of Alchornea glandulosa ethyl acetate fraction (AGF) on hydrogen peroxide (H2O2), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages activated with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) were investigated. Analysis by thin layer chromatography (TLC) of AGF showed several constituents, including flavonoids, which may have anti-inflammatory activity. Inhibitory effects of the fraction in H2O2 and NO production ranged from 8.59+/-7.84% to 70.56+/-4.16% and from 16.06+/-3.65% to 38.73+/-3.90%, respectively. The TNF-alpha production was only partially inhibited in the tested concentrations (12.21+/-6.23% - 15.16+/-0.96%). According to these results, it is suggested that AGF has anti-inflammatory activity. This medicinal plant may have therapeutic potential in the control of inflammatory disorders.
Assuntos
Euphorbiaceae/química , Peróxido de Hidrogênio/metabolismo , Macrófagos Peritoneais/metabolismo , Óxido Nítrico/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Acetatos , Animais , Sobrevivência Celular/efeitos dos fármacos , Cromatografia em Camada Fina , Peróxido de Hidrogênio/antagonistas & inibidores , Fatores Imunológicos/farmacologia , Camundongos , Extratos Vegetais , Folhas de Planta/química , SolventesRESUMO
Syngonanthus arthrotrichus SILVEIRA, popularly known as "sempre-vivas mini-saia," is found in mountains of the Espinhaço range in the Brazilian states of Bahia and Minas Gerais. Extracts of this species contain several constituents, including flavonoids which may have antiulcerogenic activity. An ethanolic extract (EEOH), and flavonoid-rich (FRF) and flavonoid-deficient (FDF) fractions obtained from the scapes of S. arthrotrichus were investigated for their ability to prevent ulceration of the gastric mucosa in mice and rats. In the ethanol/HCl-induced ulcer model, lansoprazole (30 mg/kg), EEOH (50, 100, 250 mg/kg) given orally protected the gastric mucosal against injury in mice by 79%, 78%, 73%, and 64% respectively. In the ethanol-induced gastric ulcer model in rats, the lansoprazole (30 mg/kg), FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of rats by 65%, 38% and 25% respectively when compared with the negative control group. In indomethacin/bethanechol-induced gastric ulcers, cimetidine (100 mg/kg) and the EEOH (100, 250 mg/kg) inhibited gastric ulcer formation by 73%, 55% and 32% respectively. In this exactly model other treatments as cimetidine, FRF and FDF (100 mg/kg) each caused 54%, 36% and 45% inhibition, respectively. In the stress-induced gastric ulcer model, cimetidine (100 mg/kg) and the EEOH (50, 100, 250 mg/kg), inhibited gastric ulcer formation by 63%, 73%, 68% and 69% respectively. In the same model, cimetidine, FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of the mice by 60%, 51% and 47% when compared to the control group. In pylorus-ligated mice, cimetidine (positive control) and FRF significantly decreased gastric acid secretion, increased gastric pH and reduced the acid output when compared to the negative control. FDF had no significant effect on these parameters. The protection provided by FRF probably involved an antisecretory mechanism mediated by flavonoids which were absent in FDF. The amount of adherent mucous in the stomach contents was also evaluated with the treatments carbenoxolone (200 mg/kg), FRF and FDF (100 mg/kg) treatment. Each treatments significantly increased the amount of adherent mucous in the gastric juice (8.67+/-1.73, 3.35+/-1.59, 2.1+/-0.41 mg/g of wet tissue, respectively) compared to the control group, indicating a cytoprotective action on the gastric mucosa. Treatment with FRF plus indomethacin and FDF plus indomethacin reduced the prostaglandin biosyntesis (13.6+/-6.5, 27+/-5.5 pg/well) by the mucosa, indicating that the cytoprotective action on the gastric mucosa was not related to the level of prostaglandins. Only FDF (38+/-17 pg/well) maintained the level of prostaglandins and guaranteed the integrity of the mucosa. The results indicate that the EEOH, FRF and FDF have antisecretory and cytoprotective actions, that may be related to the presence of luteoline in the extract and active fractions.