RESUMO
Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.
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This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs8-13(L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non- ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids8-13(L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.
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Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Edema/tratamento farmacológico , Peritonite/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Úlcera/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Carragenina , Celecoxib/química , Celecoxib/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Estrutura Molecular , Peritonite/induzido quimicamente , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Ratos , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia , Úlcera/induzido quimicamenteRESUMO
Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC-MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2ß-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.
Assuntos
Antiulcerosos/farmacologia , Jatropha/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Brasil , Linhagem Celular Tumoral , Diterpenos , Feminino , Masculino , Medicina Tradicional , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Sesquiterpenos , Úlcera Gástrica/induzido quimicamente , Testes de Toxicidade AgudaRESUMO
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 urtigão. 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.
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Antiulcerosos/farmacologia , Extratos Vegetais/farmacologia , Úlcera Gástrica/prevenção & controle , Urticaceae/química , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/isolamento & purificação , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos WistarRESUMO
Phycobiliproteins of Arthrospira (Spirulina) maxima have attracted attention because of their potential therapeutic antioxidant properties. The aim of this study was to assess the possible antiulcerogenic activity of these phycobiliproteins (ExPhy) against ethanol-induced gastric ulcers in rats. To explore the possible mechanisms of action, we examined antioxidant defense enzymes (e.g., catalase, superoxide dismutase, and glutathione peroxidase), as well as the level of lipid peroxidation (MDA) and the histopathological changes in the gastric mucosa. Intragastric administration of ExPhy (100, 200, and 400 mg/kg body weight) significantly lowered the ulcer index value compared to the ulcer control group (p < 0.05). The greatest protection was provided by the concentration of 400 mg/kg. The histological study supported the observed gastroprotective activity of ExPhy, showing a reduced inflammatory response. Moreover, the alcohol-induced decrease in stomach antioxidant enzyme activity found in the ulcer control group was prevented by ExPhy pretreatment. Furthermore, ExPhy reversed the ethanol-induced increase in lipid peroxidation. In summary, the antiulcerogenic potential of ExPhy may be due, at least in part, to its anti-oxidant and anti-inflammatory effects.
Assuntos
Antiulcerosos/farmacologia , Etanol , Mucosa Gástrica/efeitos dos fármacos , Ficobiliproteínas/farmacologia , Spirulina/química , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Antiulcerosos/isolamento & purificação , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Citoproteção , Modelos Animais de Doenças , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ficobiliproteínas/isolamento & purificação , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
A new furostane steroidal saponin was isolated from the leaves of Agave angustifolia var. marginata. On the basis of chemical conversions and spectroscopic analyses, its structure was established as 3-[O-ß-d-glucopyranosyl-(1â3)-O-ß-d-glucopyranosyl-(1â3)-O]-[O-6-deoxy-α-l-mannopyranosyl-(1â4)-ß-d-xylopyranosyl-(1â2)-O-ß-d-glucopyranosyl-(1â4)-ß-d-galactopyranosyl)oxy]-(3ß,5α,22α,25R)-26-(ß-d-glucopyranosyloxy)-22-methoxy-furostane (1). Results of preliminary biological investigations indicated that compound 1 showed significant protective effects against induced gastric ulcers using in vivo experimental models and demonstrated negligible toxicity on membrane integrity in the in vitro assays.
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Agave/química , Antiulcerosos/farmacologia , Saponinas/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Permeabilidade da Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Estrutura Molecular , Folhas de Planta/química , Saponinas/química , Saponinas/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Mikania laevigata leaves are commonly used in Brazil as a medicinal plant. OBJECTIVE: To obtain hydroalcoholic dried extract by nebulization and evaluate its antiulcerogenic potential. MATERIALS AND METHODS: Plant material and hydroalcoholic extract were processed and analyzed for their physicochemical characteristics. A method using HPLC was validated to quantify coumarin and o-coumaric acid. Hydroalcoholic extract was spray dried and the powder obtained was characterized in terms of its physicochemical parameters and potential for antiulcerogenic activity. RESULTS: The analytical method proved to be selective, linear, precise, accurate, sensitive, and robust. M. laevigata spray dried extract was obtained using colloidal silicon dioxide as adjuvant and was shown to possess 1.83 ± 0.004% coumarin and 0.80 ± 0.012% o-coumaric acid. It showed significant antiulcer activity in a model of an indomethacin-induced gastric lesion in mice and also produced a gastroprotective effect. CONCLUSION: This dried extract from M. laevigata could be a promising intermediate phytopharmaceutical product. SUMMARY: Research and development of standardized dried extract of Mikania laevigata leaves obtained through spray drying and the production process was monitored by the chemical profile, physicochemical properties and potential for anti-ulcerogenic activity. Abbreviations used: DE: M. laevigata spray dried extract, HE: hydroalcoholic extract.
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Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.
Assuntos
Ácido Acético , Antiulcerosos/farmacologia , Baccharis , Etanol/química , Extratos Vegetais/farmacologia , Solventes/química , Úlcera Gástrica/prevenção & controle , Estômago/efeitos dos fármacos , Animais , Antiulcerosos/isolamento & purificação , Antiulcerosos/toxicidade , Antioxidantes/farmacologia , Baccharis/química , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Ratos Wistar , Estômago/patologia , Estômago/fisiopatologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
BACKGROUND: Alpha-pinene (α-pinene) is a monoterpene commonly found in essential oils with gastroprotective activity obtained from diverse medicinal plants, including Hyptis species. The genus Hyptis (lamiaceae) consists of almost 400 species widespread in tropical and temperate regions of America. In the north and northeastern Brazil, some Hyptis species are used in traditional medicine to treat gastrointestinal disturbances. OBJECTIVE: The present study has investigated the gastoprotective effect of purified α-pinene in experimental gastric ulcer induced by ethanol and indomethacin in mice. MATERIALS AND METHODS: Gastric ulcers were induced in male Swiss mice (20-30 g) by oral administration of absolute ethanol or indomethacin 45 min after oral pretreatment with vehicle, standard control drugs or α-pinene (10, 30, and 100 mg/kg). One hour after the ulcerative challenges, the stomach were removed, and gastric lesions areas measured. The effects of α-pinene on the gastric juice acidity were determined by pylorus ligation model. The gastrointestinal motility and mucus depletion were determined by measuring the gastric levels of phenol red and alcian blue, respectively. Hematoxylin and eosin stained sections of gastric mucosa of the experimental groups were used for histology analysis. RESULTS: α-pinene pretreatment inhibited ethanol-induced gastric lesions, reduced volume and acidity of the gastric juice and increased gastric wall mucus (P < 0.05). Furthermore, we showed an interesting correlation between concentration of α-pinene and gastroprotective effect of Hyptis species (P Pearson = 0.98). CONCLUSION: Our data showed that the α-pinene exhibited significant antiulcerogenic activity and a great correlation between concentration of α-pinene and gastroprotective effect of Hyptis species was also observed.
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RESUMO As úlceras pépticas são decorrentes de um desequilíbrio entre os agentes agressores endógenos, exógenos e agentes protetores. Neste estudo avaliou-se a atividade antiulcerogênica in vivo para o extrato aquoso de Salviaofficinalis (EAS). Após os tratamentos (n = 6; v.o) com o controle (C) água; pantoprazol (30 mg/kg) e EAS (100, 250 e 400 mg/kg, respectivamente) os ratos receberam uma solução de HCl 0,3 M em etanol 60% (v.o) e realizaram-se avaliações morfológicas dos estômagos por meio de uma tabela de escores de lesão (ANOVA; one way e Tukey). EAS (400 mg/kg) apresentou atividade antiulcerogênica (31,47%) semelhante ao pantoprazol (33,83%) em comparação (p<0,0001) com o grupo C. A análise fitoquímica por cromatografia líquida de alta eficiência revelou uma elevada concentração de ácido rosmarínico (3,53%) para EAS. Os flavonoides (0,25%) e os fenóis totais (309,0 EAG) foram quantificados por espectrofotometria de UV/Vis. EAS e ácido rosmarínico apresentaram elevadas atividades antioxidantes por DPPH (Concentração Efetiva 50%-CE50 9,2 e 0,7 mg/mL, respectivamente) justificando pelo menos em parte, o efeito antiulcerogênico do extrato.
ABSTRACT Peptic ulcers are caused by an unbalance among endogenous, exogenous damaging agents and protective agents. In this study we evaluated the in vivo antiulcerogenic activity for the aqueous extract of Salvia officinalis (EAS). After treatments (n = 6; v.o) with control (C) water; pantoprazole (30 mg/kg) and EAS (100, 250 and 400 mg/kg, respectively) the rats received a 0.3 M HCl solution in ethanol 60% (v.o) and it were performed morphological evaluations of the stomachs through the use of a table of injury scores (ANOVA, one way and Tukey). The EAS (400 mg/kg) showed an antiulcerogenic activity (32.53%). Similar to the pantoprazole (29.91%), in comparison with (p<0.0001) the group C. The phytochemical analysis through high performance liquid chromatography revealed high acid rosmarinic (3.53%) for the EAS. The flavonoids (0.25%) and the total phenolics (GAE 309.0) were quantified by spectrophotometry UV/Vis. The EAS and the rosmarinic acid exhibited elevated antioxidant activities by DPPH (Effective Concentration 50% -EC50 9.2 and 0.7 mg/mL, respectively,) at least partially explaining the antiulcerogenic effect of the extract.
Assuntos
Úlcera/complicações , Extratos Vegetais/análise , Salvia/metabolismo , Polifenóis/farmacocinética , Antioxidantes/classificaçãoRESUMO
RESUMO No Brasil, a família Malvaceae está representada por aproximadamente 200 espécies e algumas foram descritas como gastroproteroras. Pavonia alnifolia A.St.-Hil. (Malvaceae) foi selecionada após uma abordagem quimiossistemática, considerando-se sua potencial capacidade em prevenir lesões gástricas. Assim, a atividade gastroprotetora do extrato etanólico de caules de P. alnifolia foi avaliada utilizando o modelo de indução aguda da lesão gástrica por etanol acidificado em camundongos. Além disso, foram quantificados o teor de flavonóides, pelo método de cloreto de alumínio, e de polifenóis, pelo método Folin-Ciocalteu, uma vez que a relação desses componentes com a proteção gástrica foi evidenciada. Os ensaios apontaram redução acentuada das lesões gástricas em camundongos tratados com o extrato da planta em todas as doses ensaiadas (10, 100 e 300 mg/kg). Esse efeito pode estar relacionado com a presença de polifenóis, cujo teor encontrado foi 74,3 ± 7,5 µg equivalente de pirogalol/mg do material vegetal examinado e 82,7 ± 7,1 µg equivalente de pirogalol /mg da amostra no extrato preparado por percolação e teor de flavonoides totais, que por sua vez apresentou um resultado de 17,1 ± 1,4 µg/mg de extrato. O extrato apresentou proteção da mucosa gástrica e este efeito pode estar relacionado à presença dos polifenóis e flavonóides encontrados
ABSTRACT Gastro protective activity of the Pavonia alnifolia A.St.-Hil. extract. In Brazil, the Malvaceae family is represented by at about 200 species. Some of those species are known as gastro protective ones. The Pavonia alnifolia A.St.-Hil (Malvaceae) was selected after a chemosystematic approach. The gastro preventive activity of the ethanol extract of stems Pavonia alnifolia was evaluated through the use of the Ethanol:chlroridric acid model on mice. The quantification of the total flavonoids (aluminum chloride method) and total polyphenols (Folin-Ciocalteu method) was also performed since the relation of those components with gastric protection has been previously highlighted. The tests showed a significant reduction of the ulcer formation in the mice treated with the plant extract (10, 100 and 300 mg/kg). This effect may be related to the presence of polyphenols whose content was found to be 74.3 ± 7.5 µg/mg of vegetal material and 82.7 ± 7.1 µg/mg of crude extract and flavonoids, which in turn showed a content of 17.1 ± 1.4 µg/mg dry extract
Assuntos
Extratos Vegetais/análise , Malvaceae/classificação , Flavonoides/análise , Polifenóis/análiseRESUMO
Gastric ulcers are a significant medical problem and the development of complications lead to significant mortality rates worldwide. In Brazil, Carthamus tinctorius L., Asteraceae, seeds essential oil, the safflower oil, is currently used as a thermogenic compound and as treatment for problems related to the cardiovascular system. In this study, by Raman spectroscopy, it was shown that oleic and linoleic acids are the compounds present in higher concentrations in the safflower oil. We demonstrated that safflower oil (750 mg/kg, p.o.) decrease the ulcerogenic lesions in mice after the administration of hydrochloric acid-ethanol. The gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) in mice treated with cholinomimetics were treated with four different doses of safflower oil, of which, the dose of 187.5 mg/kg (p.o.) showed significant antiulcerogenic properties (**p < 0.01). Moreover, the safflower oil at doses of 187.5 mg/kg (i.d.) increased the pH levels, gastric volume (**p < 0.01) and gastric mucus production (***p < 0.001), and decreased the total gastric acid secretion (***p < 0.001). The acute toxicity tests showed that safflower oil (5.000 mg/kg, p.o.) had no effect on mortality or any other physiological parameter. Ecotoxicological tests performed using Daphnia similis showed an EC50 at 223.17 mg/l, and therefore safflower oil can be considered “non-toxic” based on the directive 93/67/EEC on risk assessment for new notified substances by European legislation. These results indicate that the antiulcer activity of Safflower oil may be due to cytoprotective effects, which serve as support for new scientific studies related to this pathology.
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Introduction: species of the family Cyperaceae are commonly used by the population to treat gastric disorders.However, there are a few ethnopharmacological studies about this family Lagenocarpus rigidus (Kunth) Ness, Cyperaceae, is one of the most widespread swamp species. Objective: evaluate the gastric activity of L. rigidus and its chemical characterization. Methods: ethanolic extract of L. rigidus (ELR) leaves prepared by percolation was subjected to total polyphenol and flavonoid quantification, as well as HPLC quantification of some flavonoids. Angiotensin converting enzyme (ACE) inhibition was determined by colorimetric assays.The gastric effects of ELR were tested in male Wistar rats (n = 6 each group) treated with different doses (600, 60 and 6 mg/kg i.p.) ELR.Gastric lesions were induced by administration of indomethacin (30 mg/kg s.c.).The number of ulcers and the index of mucosal damage (IMD) were determined taking into account the color, edema and bleeding of gastric lesions, the number of petechiae, and the number and size of the ulcers. Statistical analysis of data was performed with one-way ANOVA followed by Tukey's test; significance was p < 0.05. Results: ELR inhibited the ACE (68.5±18.1%) at a concentration of 100 mg/mL.Oral administration of ELR (6, 60 and 600 mg/kg) showed protective activity against indomethacin-induced gastric injury. Total polyphenols in ELR were 157.7 ± 5.8 mg pirogalol/mg equivalent flavonoids and 66.9 ± 3.1 µg equivalent quercetin/mg. Conclusion: L. rigidus protects against acute gastric damage induced by indomethacin in an independent dose manner.
Introducción: las especies de la familia Cyperaceae popularmente se utilizan para tratar trastornos gástricos. Sin embargo, hay pocos estudios etnofarmacológicos sobre esta familia. Lagenocarpus rigidus (Kunth) Ness, Cyperaceae, es una de las especies más grandes de población en pantano. Objetivo: evaluar la actividad gástrica de L. rigidus, junto a su caracterización química. Métodos: el extracto etanólico de hojas de L. rigidus (ELR), preparado por percolación fue objeto de cuantificación de polifenoles y flavonoides totales, cuantificación por HPLC de algunos flavonoides. La inhibición de la enzima convertidora de angiotensina (ECA) se realizó por ensayos colorimétricos. Los efectos gástricos de ELR se llevó a cabo en ratas Wistar macho (n = 6, cada grupo), el tratamiento con diferentes dosis (600, 60 y 6 mg/kg ip) de ELR. Las lesiones gástricas se indujeron mediante la administración de indometacina (30 mg/kg sc). El número de úlceras y signos de puntuación del índice de lesión de las mucosas (IMD) se evaluó teniendo en cuenta el color, edema y hemorragia de las lesiones gástricas, el número de petequias, y el número y tamaño de las úlceras. El análisis estadístico de los datos se realizó mediante ANOVA 1 vía, seguido por el test de Tukey y significación fue de p < 0,05. Resultados: ELR inhiben la ACE (68,5 ± 18,1 %) a una concentración de 100 mg/mL. La administración oral de ELR (6, 60 y 600 mg/kg) mostró un efecto protector gástrico contra inducido por indometacina. Los polifenoles totales de ELR fue 157,7 ± 5,8 mg equivalente de pirogalol/mg de flavonoides y 66,9 ± 3,1 μg equivalentes de quercetina/mg. Conclusiones: L. rigidus protege contra el daño gástrico agudo inducido por la indometacina en una organización independiente de la dosis.
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Ethnobotanical claims regarding Kigelia africana reported antiulcer properties as part of its medicinal application. In this work, aqueous leaf extract from K. africana was investigated for its phytochemical constituents and antiulcer potential against ethanol-induced ulcer in rats. The participation of oxidative stress on ethanol-induced ulcer and the potential protective antioxidant activity of K. africana extracts were investigated by determining vitamin C and thiobarbituric acid reactive species (TBARS) contents in the gastric mucosa of rats. The HPLC analysis showed the presence of gallic acid, chlorogenic acid, caffeic acid and also the flavonoids rutin, quercetin and kaempferol in the aqueous plant extract. Oral treatment with K. africana extract (1.75; 3.5; 7 and 14 mg/kg) one hour after ulcer induction with ethanol decreased in a dose dependent manner the ulcer index. Ethanol increased significantly stomachal TBARS levels and decreased vitamin C content when compared to the control animals. K. africana blunted the ethanol-induced oxidative stress and restored vitamin C content to the control levels. The present results indicate that the aqueous leaf extract from K. africana possesses antiulcer potential. The presence of flavonoids in plant extract suggests that its antiulcerogenic potential is associated with antioxidant activity. Of particular therapeutic potential, K. africana was effective against ethanol even after the induction of ulcer, indicating that it can have protective and curative effects against gastric lesion.
RESUMO
The Celtis iguanaea (Jacq.) Sargent (Cannabaceae) is one of the native species of the Cerrado region of Brazil widely used in folk medicine to treat dyspepsia. The objective of the present study was to evaluate the gastroprotective effect of the Celtis iguanaea (Jacq.) Sargent (HE) hexane leaf extract in the lesion and gastric secretion models.Antiulcerogenic activity of the Celtis iguanaea (HE) hexane leaf extract was observed with the experimental models, such as indomethacin and pyloric ligation-induced gastric ulcers. In order to evaluate the antisecretory activity of this extract, isolated Rana catesbeiana mucosa and pyloric ligation in mice were used. The HE treatment reduced the lesion index of indomethacin and pyloric ligation-induced ulcer. This extract also reduced the gastric acid secretion and total acidity (increasing the gastric pH) in mice. The secretion of H+ was reduced in the basal values (15.58 ± 1.99 µEq H+/g/15 min) when isolated Rana catesbeiana mucosa was incubated with HE. Intraduodenal administration of HE reduced the gastric secretion produced by bethanecol or histamine. The antiulcerogenic and antisecretory efficacy of HE in this study suggest anticholinergic and antihistaminergic mechanism or interruption of intracellular events that are linked to acid secretion.
Celtis iguanaea (Jacq.) Sargent (Cannabaceae) é uma das espécies nativas do cerrado brasileiro, sendo amplamente utilizada na medicina popular para o tratamento de dispepsia. O objetivo do presente trabalho foi avaliar o efeito gastroprotetor do extrato hexânico das folhas de Celtis iguanaea (Jacq.) Sargent (EH) em modelos de secreção e de lesões gástricas. A atividade antisecretória do extrato hexânico das folhas de Celtis iguanaea (EH) foi avaliada no modelo de mucosa isolada de Rana catesbeiana e pelo modelo de ligadura pilórica em camundongos. A avaliação da atividade anti-ulcerogênica do EH foi determinada no modelo de úlceras gástricas induzidas por indometacina e ligadura pilórica. Quando a mucosa de Rana catesbeiana isolada foi incubada com o EH, a secreção de H+ foi reduzida em comparação com o valor basal (15,58 ± 1,99 µEq H+/g/15 min). O tratamento com o EH reduziu o índice de lesões na úlcera induzida por indometacina e ligadura pilórica. O EH também reduziu o volume de secreção, a acidez total, e aumentou o pH gástrico. A administração intraduodenal reduziu a secreção gástrica produzida por betanecol ou histamina. A eficácia anti-ulcerogênica e antisecretória do EH neste estudo, sugere um mecanismo anticolinérgico e antihistaminérgico ou interrupção de eventos intracelulares que estão ligados à secreção ácida.
Assuntos
Animais , Masculino , Feminino , Ratos , Extratos Vegetais/análise , Cannabaceae/classificação , Rana catesbeiana , Úlcera Gástrica , PradariaRESUMO
Bryophyllum pinnatum (Lam.) Kurz pertence a família Crassulaceae e é conhecida vulgarmente como coirama, folha-da-fortuna, ou folha-do-ar, sendo usada popularmente como antifúngico, no tratamento da hipertensão, em úlceras e em inflamações. O presente estudo objetivou analisar a atividade antiulcerogênica do extrato aquoso das folhas de Bryophyllum pinnatum (Lam.) Kurz em modelo de úlcera gástrica induzida por indometacina em Rattus norvegicus, machos (150 a 250 g) com idade de 70 dias. Os animais receberam por via oral: água, extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz (1 e 2 g Kg-1 ) ou ranitidina (60 mg Kg-1 ), fármaco com ação gastroprotetora conhecida que atua bloqueando os receptores de histamina H2. Após uma hora dos tratamentos, todos animais receberam indometacina via intraperitoneal. Os resultados demonstraram que o extrato aquoso da Bryophyllum pinnatum (Lam.) Kurz possui ação gastroprotetora; na dose de 1 g Kg-1 inibiu 45,49% o índice de ulceração induzido pela indometacina, e, na dose de 2 g Kg-1, inibiu 49,50%. Sugere-se o envolvimento de vários mecanismos na ação gastroprotetora dessa planta e não somente uma possível participação das prostaglandinas nesse efeito. Estudos futuros com diferentes modelos de indução de úlcera gástrica tornam-se necessários para melhor avaliar a atividade antiulcerogênica do extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz.
Bryophyllum pinnatum (Lam.) Kurz belongs to the family Crassulaceae, is popularly known as "coirama", "folha-da-fortuna", or "folha-do-ar" and has been commonly used as antifungal, in the treatment of hypertension, ulcers and inflammation. The present study aimed to analyze the antiulcerogenic activity of aqueous extract from the leaves of Bryophyllum pinnatum (Lam.) Kurz using indomethacin-induced gastric ulcer models in Rattus norvegicus, males (150-250 g) aged 70 days old. The animals received by the oral route: water, aqueous extract from Bryophyllum pinnatum (Lam.) Kurz (1 and 2 g Kg-1) or ranitidine (60 mg Kg-1), a drug with known gastroprotective action, blocking histamine H2-receptors. After one hour of treatments, all animals received indomethacin by the intraperitoneal route. Results demonstrated that the aqueous extract from Bryophyllum pinnatum (Lam.) Kurz has gastroprotective action; at 1g kg-1 it inhibited 45.49% of the indomethacin-induced ulcer index, while at 2g Kg-1 it inhibited 49.50%. Several mechanisms of actions are suggested to be involved in the gastroprotective action of this plant, besides the possible participation of prostaglandins in this effect. Further studies using different gastric ulcer-induction models are needed to better evaluate the antiulcerogenic activity of aqueous extract from Bryophyllum pinnatum (Lam.) Kurz.
Assuntos
Animais , Masculino , Ratos , Extratos Vegetais/análise , Kalanchoe/fisiologia , Gastrite/fisiopatologia , Plantas Medicinais/classificação , Fármacos Gastrointestinais , Componentes Aéreos da Planta , Gastroenteropatias/tratamento farmacológicoRESUMO
Ethanolic extract of Annona muricata L., Annonaceae, leaf (AML) was used to investigate its antinociceptive and anti-ulcerogenic activities and the involvement of the mechanism of ethanolic leaves extract of AML in various animal models. Antinociceptive activity of AML extract was done using acetic acid-induced abdominal writhing in mice, formalin test in rats and hot plate test in mice. Furthermore, the anti-ulcerogenic effect of AML extract was studied in ethanol-induced ulcer model in rats, ethanol-induced gastric lesions in L-NAME-pre-treated rats as well as ethanol-induced gastric lesions in NEM-pre-treated rats test model to determine its mechanism. AML exhibited significant and dose-dependent antinociceptive activity. It also significantly decreased the ulcerative lesion produced by ethanol in rats in a dose-dependent manner. Pre-treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anti-ulcerogenic effect of AML extract in the same ulcer model, suggesting that AML extract may have active substances such as tannins, flavanoids and triterpenes that increase the mucosal nonprotein sulfhydryl group content.
RESUMO
Syzygium jambos (L.) Alston, Myrtaceae, é empregado na medicina popular como digestivo e antiinflamatório. A triagem fitoquímica da droga pulverizada (folhas) indicou a presença de flavonóides, taninos e óleo volátil. O extrato hidroetanólico a 70 por cento das folhas de S. jambos foi preparado por percolação e liofilizado. O conteúdo de taninos das folhas e do extrato foi calculado, respectivamente, em 21,9 por cento e 43,3 por cento. O teor de flavonóides foi de 0,6 por cento (folhas) e 1,2 por cento (extrato). A administração oral prévia do extrato (400 mg/kg) a ratos Wistar reduziu significativamente as lesões gástricas induzidas por etanol acidificado. No modelo de úlcera subcrônica, com indução de lesão gástrica utilizando ácido acético a 30 por cento, o tratamento com o extrato (400 mg/kg) não apresentou resultado significativo. A atividade antioxidante do extrato foi avaliada através dos modelos de lipoperoxidação e de medida de capacidade seqüestrante de radicais DPPH. Os valores obtidos de Q1/2 (MDA) e CE50 (DPPH) foram, respectivamente, 0,17 μg/mL e 5,68 μg/mL.
Syzygium jambos (L.) Alston, Myrtaceae, is commonly employed in folk medicine as digestive and anti-inflammatory. Phytochemical screening of the powdered dried leaves indicates the presence of flavonoids, tannins and essential oil. Hydroethanol extracts (70 percent) were prepared by percolation and freeze-drying. The tannin content of dried leaves and extract was, respectively, 21.9 percent and 43.3 percent. The flavonoid content was 0.6 percent (dried leaves) and 1.2 percent (extract). Previous oral administration of S. jambos leaves extract (400 mg/kg) to rats reduced significantly gastric injury induced by HCl/ethanol. At the subcronic ulcer model by induction with 30 percent acetic acid the results were not significant. In vitro antioxidant activity of S. jambos extract was evaluated by malondialdehyde (MDA) and DPPH free radical method. The Q1/2 for MDA assay was 0.17 μg/mL and the EC50 for DPPH assay was 5.68 μg/mL.
RESUMO
O extrato metanólico bruto (EMeOH) das partes aéreas da Herissantia crispa (L.) Brizicky, planta rica em flavonóides e que não possui estudos farmacológicos, foi testada para avaliar sua atividade sob os parâmetros comportamentais e determinar a dose letal 50 (DL50) em camundongos; atividade antimicrobiana e antiulcerogênica. O EMeOH (5000 mg/kg, v.o. ou 2000 mg/kg i.p.) não alterou os parâmetros comportamentais e não causou mortes nos animais. A amostra vegetal em estudo inibiu o crescimento bacteriano. O EMeOH (750 mg/kg) apresentou atividade anti-diarréica. O EMeOH (250, 500 e 750 mg/kg) foi capaz de inibir as lesões gástricas induzidas pelo 0,3 M HCl/etanol 60 por cento em camundongos. Desta forma, pode-se concluir que a planta em estudo apresenta atividade antiulcerogênica, entretanto, se faz necessário avaliar tal atividade através de modelos mais específicos e estudar o mecanismo de ação pelo qual a amostra vegetal protege a mucosa gástrica.
The crude methanol extract (EMeOH) of the aerial parts of Herissantia crispa (L.) Brizicky, plant riches in flavonoids and without pharmacological studies, was tested to value its activity under the behaviour parameters and to determine the lethal dose (LD50) in mice; antimicrobial and antiulcerogenic activities. The EMeOH (5,000 mg/kg, v.o. or 2,000 mg/kg i.p.) did not alter the behaviour parameters and there were not mice deaths. The extract inhibited the bacterial growth. The EMeOH (750 mg/kg) showed anti-diarroeal activity. The EMeOH (250, 500 and 750 mg/kg) decreased the gastric lesions induced by 0.3 M HCl/ethanol 60 percent in mice. In conclusion, the EMeOH presents anti-ulcerogenic activity;, however it is necessary to value the antiulcerogenic activity in more specific models and to study the action mechanism by which the vegetable sample protects the gastric mucosa.
RESUMO
O presente trabalho investigou as propriedades antinociceptiva, antiinflamatória e antiulcerogênica do extrato etanólico dos galhos de E. erythropappus. Foram realizados os testes de contorções abdominais induzidas por ácido acético; tempo da lambida da pata induzida por formalina; placa quente; edema de pata induzido por carragenina; lesões ulcerativas induzidas por indometacina e etanol. As doses de 50, 100 e 200 mg/kg inibiram as contorções em 43,07 por cento, 69,34 por cento e 70,07 por cento, respectivamente. O tempo da lambida da pata foi reduzido em ambas as fases nas doses testadas, enquanto o tempo de latência da placa quente teve efeito significativo na dose de 200 mg/kg. O edema de pata foi reduzido em 23,81 por cento (100 mg/kg) e 47,62 por cento (200 mg/kg). O índice ulcerativo das lesões induzidas por indometacina foi reduzido na dose de 100 mg/kg e 200 mg/kg, enquanto a dose de 200 mg/kg teve efeito significativo sobre o volume e o pH do suco gástrico. O índice ulcerativo e o volume do suco gástrico, induzidos por etanol, foram reduzidos na dose de 200 mg/kg, enquanto o pH do suco gástrico aumentou nas doses de 100 e 200 mg/kg. Os resultados indicam que o extrato etanólico de E. erythropappus avaliado pode constituir alvo potencial para uso em terapias da dor, da inflamação e de úlcera.
The present work investigated the antinociceptive, anti-inflammatory and antiulcerogenic activities of Eremanthus erythropappus ethanol extract. The tests were carried out by acetic acid writhing, paw licking induced by formalin, hot plate, indomethacin- and ethanol-induced ulcer. The doses of 50, 100 and 200 mg/kg inhibited the contortions in 43.07, 69.34 and 70.07 percent, respectively. Both phases of paw lick were reduced at the tested doses, while reaction time at hot plate had significant effect at 200 mg/kg. The paw edema was decreased in 23.81 percent (100 mg/kg) and 47.62 percent (200 mg/kg). The index of ulceration induced by indomethacin was reduced at the doses of 100 and 200 mg/kg, while 200 mg/kg decreased the gastric volume and pH. The index of ulceration and gastric volume induced by ethanol was reduced at 200 mg/kg, while the pH increased at 100 and 200 mg/kg. The results indicate that the ethanol extract from E. erythropappus may constitute a potential target for the use in therapies of the pain, inflammation and ulcer.