GASTRO PROTECTIVE AND ANTI-HELICOBACTER PYLORI EFFECTS OF A FLAVONOID RICH FRACTION OBTAINED FROM ACHYROCLINE SATUREOIDES (LAM) D.C.

Objectives: The study aimed to investigate the gastroprotective effects of a flavonoid rich fraction (FRF) obtained from Achyrocline satureoides. Methods: The following protocols were employed: ethanol and NSAID-induced ulcer, ligature pylorus model, and free mucus quantification. Nitric oxide (NO) and sulfhydryl group participation were observed by pretreatment with L-NAME or NEM. Besides, it was assayed the acetic acid-induced chronic ulcer andthe anti-Helicobacter pyloriactivity in vitro. Results: The phytochemical profile of FRF showed three main flavonoids, luteolin, quercetin and 3-O-methyl-quercetin. The administration of FRF was able to prevent the damage evoked by ethanol and NSAID-induced ulcer models. The pH and concentration of H+ in the stomach were not modified by FRF treatment. However, the FRF treatment induces mucus secretion. The effect presented by FRF was mediated by nitric oxide (NO). In chronic ulcer model FRF reduced significantly the lesion area, promoting a cure ratio of 65.42±13.00, a similar data presented by cimetidine treated animals (61.35±11.88). Using an in vitro assay was observed that FRF at 500 µg/mL was able to inhibit bacterial growth. Conclusions: The results show that FRF provided a significant gastroprotective and ulcer healing activity, mainly due to their capacity to enhance mucus secretion

Nerolidol, an Antiulcer Constituent from the Essential Oil of Baccharis dracunculifolia DC (Asteraceae)

In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol. The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono-and sesquiterpenes and the majority compound was nerolidol. Therefore, antiulcerogenic activity of nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin-and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p Ͻ 0.05). The percentage of inhibition of ulcer was 41.22, 51.31, 56.57 and 53.50% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. Regarding ethanol-and indomethacin-induced ulcer models, it was observed that the treatment with nerolidol (250 and 500 mg/ kg) significantly reduced the ULI in comparison with the control group (p Ͻ 0.05). The dose of 50 mg/kg reduced the parameters analyzed but this was not statistically significant. In the ethanol-induced model percentage of inhibition of ulcer was 34.20, 52.63, 87.63 and 50.87% in groups treated with 50, 250, 500 mg/kg of nerolidol and 30 mg/kg of omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/ kg of cimetidine (positive control), respectively. The results of this study show that nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of nerolidol for the treatment of gastric ulcer

Toxicological and pharmacological prospection in vitro and in vivo oil resins, leaf extracts and isolated compounds from Copaifera oblongifolia Mart. ex Hayne and C. duckei Dwyer

Plantas medicinais são uma fonte rica na obtenção de moléculas com potencial terapêutico. No Brasil cerca de 40% da população utiliza plantas medicinais como alternativa terapêutica. Porém, grande parte das plantas nativas brasileiras não apresentam estudos científicos que comprovem a eficácia e a segurança. Além disso, devido à enorme biodiversidade, o número de espécies estudas ainda é pequeno, e representa um vasto campo a ser explorado. Neste contexto, as oleorresinas de planta do gênero Copaifera apresentam poucos estudos sob o ponto de vista químico, farmacológico e toxicológico. Suas partes aéreas, tais como folhas os estudos ainda são escassos. Dentro deste contexto, este projeto buscou avaliar a toxicologia de oleorresinas e extratos das folhas de C. oblongifolia Mart. ex Hayne e C. duckei Dwyer, e compreender preliminarmente os mecanismos envolvidos nos processos de citoproteção e cicatrização de úlceras gástricas, bem como os processos antiinflamatórios e antinociceptivos, atribuídos popularmente e previamente descritos na literatura para a oleorresina das copaíbas. Além disso, existem poucos estudos para C. oblongifolia Mart. ex Hayne e C. duckei Dwyer. Com base nos padrões de fragmentação obtidos nas análises em CG-MS e em UHPLC-(ESI)-HRMS permitiu concluir que as oleorresinas apresentam compostos da classe de sesquiterpenos e diterpenos, assim como descrito na literatura. Nos extratos das folhas foi possível observar a presença de flavonoides e derivados galoilquínicos, já descritos para as folhas da espécie, e epicatequinas, descrito na família Fabacea, mas não isolado ainda em espécies de Copaifera spp. Os resultados dos ensaios a atividade citotóxica em linhagens não neoplásicas (CHO-k1 e L929) e neoplásicas (AGS e THP-1) por meio do ensaio de viabilidade celular por fosfatase ácida, e no ensaio de morte celular determinada por iodeto de propídio em citometria de fluxo para as células AGS e THP- 1 demonstram que as oleorresinas, extratos e substâncias isoladas de C. oblongifolia e C. duckei apresentam atividade citotóxica preferencial em células neoplásicas, confirmando a atividade antitumoral já descrita na literatura. Na avaliação da toxicidade aguda por dose fixa, o extrato das folhas de C. oblongifolia, C. duckei e o ácido polialtico são seguros até a dose de 2000 mg/kg. A administração da oleorresina promove alterações hematológicas, bioquímicas e histológicas, principalmente ligadas ao metabolismo hepático, renal e pancreático. A oleorresina de C. duckei é tóxica na dose de 2000 mg/kg, promovendo a morte dos animais após 48 h da sua administração. No experimento com doses repetidas em 90 dias não houve morte dos animais tratados com 1, 10 e 100 mg/kg de oleorresina de C. duckei, porém houveram alterações hematológicas, bioquímicas e histológicas, embora menos evidente, no metabolismo hepático, renal e pancreático. Quanto a gastroproteção, as oleorresinas e os extratos das folhas de C. oblongifolia e C. duckei promovem efeitos citoproterores sobre a mucosa gástrica nos modelos de EtOH/HCl e AINEs. As frações em diclorometano e acetato de etila do extrato das folhas de ambas as espécies de Copaifera spp. contêm os compostos que podem ser responsáveis pela citoproteção gástrica. Sesquiterpenos, diterpenos, flavonoides e derivados galoilquínicos também foram avaliados, demonstrando atividades gastroprotetoras no modelo de úlceras induzidas por EtOH/HCl. Tanto a oleorresina quanto o extrato das folhas de C. xi oblongifolia e C. duckei apresentam atividade cicatrizante gástrica no modelo de úlceras induzidas por ácido acético, e aumentam a proliferação celular no ensaio de wound scratch em L929. A oleorresina de C. oblongifolia e C. duckei não contribui para o aumento do pH estomacal, mas diminuiu a quantidade de íons H+ secretada. Os extratos das folhas de C. oblongifolia e C. duckei aumentaram significativamente a quantidade de muco, favorecendo as defesas gástricas. A oleorresina e o extrato das folhas de C. oblongifolia são ativas contra a bactéria H. pylori, tanto in vitro, quanto in vivo. Os extratos de C. oblongifolia e C. duckei possuem maior atividade antioxidante - in vitro e in vivo - quando comparados à oleorresina. Em parte, os metabólitos presentes nas oleorresinas e nos extratos das folhas de C. oblongifolia e C. duckei promovem efeitos citoprotetores e cicatrizantes, interferindo na secreção de ácido, conforme demonstrado no ensaio sobre a enzima H+, K+-ATPase, aumentando a secreção de muco e favorecendo os mecanismos de defesa antioxidantes. Procurando verificar se a atividade antinociceptiva estava relacionada a ação no SNC dos animais, avaliaram-se as oleorresinas e os extratos das folhas das espécies de Copaifera spp. na função e coordenação motora dos animais, através dos testes de Open field e Rota rod. Nenhum tratamento interferiu na função e na coordenação motora dos animais. A oleorresina de C. duckei e sua substância majoritária, o ácido poliáltico foram testados quanto a atividade anti-inflamatória e antinociceptiva, tanto sob o ponto de vista agudo, quanto crônico. Foram utilizados os métodos de contorções abdominais por ácido acético, nocicepção aguda por formalina, nocicepção térmica por tail-flick, hiperalgesia mecânica, edema de pata e air pouch (avaliação do exsudato na bolsa de ar) induzida por diversos agentes, tais como formalina, carragenina, dextrana, LPS e zymosan. Além disso, foram investigadas de forma preliminar as atividades contra dor crônica induzida por avulsão do plexo braquial (APB) e hipernocicepção induzida por CFA durante 15 dias. Em todos os ensaios houve redução tanto da resposta nociceptiva quanto da atividade inflamatória, sugerindo que há ação antinociceptiva a nível periférico, ou por inibição do sinal nociceptivo ou pela diminuição de mediadores que estimulam os nociceptores, que diminuir a migração celular e a concentração de mieloperoxidase (MPO) no local da lesão. Em células THP-1 estimuladas por LPS, os tratamentos com as oleorresinas, extratos e substâncias majoritárias de C. oblongifolia e C. duckei diminuíram os níveis de citocinas pró-inflamatórias INF-?, IL-1?, IL-6 e TNF-?. Os níveis de IL-10 foram parcialmente reduzidos com estes tratamentos. A ação sobre citocinas próinflamatórias sugere atividade anti-inflamatória tanto aguda quanto crônica, tendo em vista que o experimento possui os tempos de 24 h e 72 h e esta diminuição é dose dependente. Além disso, a oleorresina de C. duckei e o ácido poliáltico interferem nos níveis de NF-?B determinados no ensaio da luciferase. Estes resultados indicam que pode estar havendo interação com os receptores TLR4 e TLR2, que interferem na via do NF-?B e diminuem os eventos inflamatórios e apoptóticos oriundos desta via, confirmando as atividades estudadas. As atividades antinociceptivas e antiinflamatórias observadas no tratamento com a oleorresina de Copaifera spp. ou suas substâncias isoladas podem ser devido a diminuição da liberação ou síntese de mediadores relacionados à resposta inflamatória, que resulta em diminuição do estímulo nociceptivo. As atividades citotóxicas descritas indicam que existe potencial efeito antitumoral que justifica o estudo para o desenvolvimento de substâncias com atividade antitumoral, em especial atenção para os cânceres gástricos e ligados ao sistema imunológico, tendo em vista a seletividade citotóxica em linhagens tumorais AGS e THP-1. Os resultados apresentados neste trabalho são inéditos, tendo em vista que é escasso na literatura dados sobre a C. oblongifolia, e dados sobre o uso a longo xii prazo de oleorresinas e extratos de Copaifera. Além disso, os achados fitoquímicos sugerem que existe potencial investigação química, pois muitas substâncias ainda não foram isoladas das espécies. Ainda, estes resultados contribuem para a confirmação das atividades farmacológicas atribuídas popularmente para as espécies de Copaifera spp., sendo que pela primeira vez observou-se que a oleorresina é efetiva para o tratamento de doenças inflamatórias e dolorosas crônicas, tornado a planta alvo para o estudo mais aprofundado dos mecanismos de ação farmacológicos envolvidos, fornecendo subsídios para estudos posteriores que poderão servir ao desenvolvimento de um novo fitoterápico no Brasil.Medicinal plants are a rich source of potentially bioactive molecules. In Brazil, about 40% of the population use medicinal plants as an alternative therapy. However, most Brazilian native plants have no scientific studies proving their effectiveness and safety. Additionally, due to the enormous Brazilian biodiversity, the number of studied species is still small, and it represents a vast field to be explored. In this context, oleoresins from plants belonging to the genus Copaifera have few studies regarding its chemical, pharmacological and toxicological properties. For its aerial parts such as leaves, the studies are also scarce. Within this context, this project sought to assess the toxicology of oleoresins and leaf extracts of C. oblongifolia Mart. ex Hayne and C. duckei Dwyer, and understand preliminarily the mechanisms involved in wound healing processes and cytoprotection of gastric ulcers, as well as the anti-inflammatory and antinociceptive processes, commonly assigned and previously described in the literature for the copaiba oleoresin. Furthermore, there are few studies of C. oblongifolia Mart. ex Hayne and C. duckei Dwyer. Based on the fragmentation patterns obtained in the GC-MS and UHPLC-(ESI)-HRMS analyses it was concluded that oleoresins possess compounds of the sesquiterpene and diterpene class, as described in the literature. In leaf extracts, it was observed the presence of flavonoids and galoilquinic acid derivatives, as previously described for the leaves of this species, and epicatechins, described in the Fabaceae family, but not reported thus far in species of Copaifera spp. The results of the cytotoxic tests on neoplastic (AGS and THP-1) and non-neoplastic lines (CHO-k1 and L929) by cell viability assay for acid phosphatase, and cell death assay determined by propidium iodide in flow cytometry for AGS and THP-1 cells demonstrate that oleoresins, extracts and compounds isolated from C. oblongifolia and C. duckei present preferred cytotoxic activity on neoplastic cells, thus confirming the antitumor activity already described in literature. In the evaluation of acute toxicity by a fixed dose, leaf extracts from C. oblongifolia, and C. duckei and polyalthic acid are safe at doses up to 2000 mg / kg. The administration of oleoresin promotes hematological, biochemical and histological changes, mainly linked to liver, kidney and pancreatic metabolism. C. duckei oleoresin is toxic at a dose of 2000 mg / kg, promoting death of animals after 48 hours of its administration. In the experiment with repeated doses in 90 days there was no death of animals treated with 1, 10 and 100 mg / kg of C. duckei oleoresin, but there were hematological, biochemical and histological changes, although less obvious, in hepatic, renal and pancreatic metabolism. Regarding gastroprotection, the oleoresins and extracts from C. oblongifolia and C. duckei leaves promote cytoprotective effects on gastric mucus in EtOH/HCl and NSAIDs models. The dichloromethane and ethyl acetate fractions from crude leaves extract of both species Copaifera spp. contain compounds which may be responsible for gastric cytoprotection. Sesquiterpenes, diterpenes, flavonoids and galoilquinic acid derivatives were also evaluated, demonstrating gastroprotective activities in the model of ulcers induced by EtOH/HCl. Oleoresin and leaf extracts from C. oblongifolia and C. duckei present gastric healing activity in the model of ulcers induced by acetic acid, and increase cell proliferation in the L929 wound scratch assay. C. oblongifolia and C. duckei oleoresin do not increase the stomach pH, but decrease the amount of H + ions secreted. C. oblongifolia and C. duckei leaf extracts significantly increased the quantity of mucus, favoring gastric defense. Oleoresin and leaf extract of C. oblongifolia are active against the bacteria H. pylori, both in vitro and in vivo. C. oblongifolia and C. duckei leaf extracts have higher antioxidant activity - in vitro and in vivo - compared to their oleoresins. In part, the metabolites present in oleoresins and in leaf extracts of C. oblongifolia and C. duckei promote healing and cytoprotective effects, interfering in the secretion of acid, as demonstrated in enzyme test against H +, K + -ATPase, increasing the secretion of mucus and favoring the antioxidant defense mechanisms. In order to verify whether the antinociceptive activity was related to ab effect in the CNS of animals, we evaluated oleoresins and leaf extracts in the function and motor coordination of animals, through the Open field and Rota rod test. No treatment interfered in the function and motor coordination of animals. C. duckei oleoresin and its major substance, polyalthic acid were tested for anti-inflammatory and antinociceptive activity, both in the acute and chronic models. Different methods were used such as writhing by acetic acid, acute nociception formalin, thermal nociception by tail-flick, mechanical hyperalgesy, paw edema and air pouch (exudate assay in air pouch) induced by various agents, such as formalin, carrageenan, dextran, zymosan and LPS. Additionally, there were preliminarily investigated activities against chronic pain induced by brachial plexus avulsion (APB) and hyperalgesy induced by CFA for 15 days. In all experiments there was a reduction of in nociceptive response and inflammatory activity, suggesting that there is antinociceptive activity in the peripheral level, by inhibition of the nociceptive signal or by a decrease of mediators that stimulate nociceptors, which decrease cell migration and concentration of myeloperoxidase (MPO) at the site of injury. In THP-1 cells stimulated by LPS, treatments with oleoresins, extracts and Major compounds from C. oblongifolia and C. duckei decreased levels of proinflammatory cytokines INF-?, IL-1?, IL-6 and TNF-?. IL-10 levels were partially reduced with these treatments. The action of proinflammatory cytokines suggests both acute and chronic anti-inflammatory activity, considering that the experiment has the times of 24 h and 72 h and this decrease is dose-dependent. Furthermore, C. duckei oleoresin and polyalthic acid and interfere with NF-?B levels determined in the luciferase assay. These results indicate that there may be an interaction with the TLR4 and TLR2 receptors that affect the NF-?B pathway and decrease the inflammatory and apoptotic events from this pathway, confirming the studied activities. The antinociceptive and anti-inflammatory activity observed in the treatment with Copaifera spp oleoresin. or its isolated substances may be due to a decrease in the release or synthesis of mediators related to the inflammatory response, which results in a decreased nociceptive stimulus. The described cytotoxic activities indicate that there is potential antitumor effect that justifies the study for the development of substances having antitumor activity, especially regarding to gastric cancers and those related to the immune system, considering the cytotoxic selectivity in AGS and THP-1 tumor cell lines. The results presented herein are new, considering the scarce studies regarding C. oblongifolia, and long-term use of oleoresins and extracts from Copaifera. Moreover, phytochemicals findings suggest that there is potential in the chemical research, as many substances have not yet been isolated from these species. Furthermore, these results contribute to the confirmation of the pharmacological activities assigned commonly to the species of Copaifera spp., and this is the first time that oleoresins are found to be effective for the treatment of chronic inflammatory and painful disorders. Thus, this study makes the studied plants an alternative target for further studies concerning the pharmacologic mechanisms of action involved, providing support for further studies that will serve for the development of a new phytotherapy medicine in Brazil

Evaluation of the genotoxic and antigenotoxic potential of Brassica oleracea L. var. acephala D.C. in different cells of mice

Ethnopharmacological relevance: Brassica oleracea L var. acephala D.C. has been extensively used in Brazilian traditional medicine to treat gastric ulcer.Aim of the study: This study was conducted to evaluate the in vivo genotoxic and/or antigenotoxic potential of a Brassica oleraceae hydroalcoholic extract obtained from the leaves, in different cells of mice.Materials and methods: Analyses were performed using the comet assay, on leukocytes (collected 4 and 24 h after treatment), liver, brain, bone marrow and testicular cells (collected 24 h after treatment), and using the micronucleus test (MN) in bone marrow cells. Eight groups of albino Swiss mice were treated (N=6): control (C), positive control (doxorubicin 80 mg/kg (DXR)), and six experimental groups, which received 500, 1000 and 2000 mg/kg of Brassica oleraceae extract alone by gavage, while a further three groups received the same doses plus DXR (80 mg/kg). We calculated the damage scores, and their averages were compared by ANOVA followed by the Tukey test for multiple comparisons.Results: The results demonstrated that none of the tested doses of Brassica oleraceae extract showed genotoxic effects by the comet assay, or clastogenic effects by the MN test. on the other hand, for all cells evaluated, the three tested doses of the Brassica extract promoted inhibition of DNA damage induced by DXR.Conclusions: Under our experimental conditions, Brassica oleraceae leaf extract showed no genotoxic or clastogenic effects in different cells of mice. However, it did show a significant decrease in DNA damage induced by doxorubicin. It is suggested that the antigenotoxic properties of this extract may be of great pharmacological importance, and may be beneficial for cancer prevention. (C) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Experimental skin wound treatment with Copaifera langsdorffii Desf Kuntze (Leguminosae) extract and oil-resin in horses

Copaifera langsdorffii é uma planta nativa brasileira usada para cicatrização de feridas e como agente anti-inflamatório. As feridas que não cicatrizam são um importante problema de saúde em equinos, devido à possibilidade de afastamento da carreira atlética ou até mesmo levar à morte. Além disso, os cavalos respondem às feridas com resposta inflamatória crônica e intensa granulação, atrasando o processo cicatricial. Dessa forma, o presente trabalho avaliou o potencial do extrato hidroalcoólico (EH) e cremes de óleo resina (OR) de Copaifera langsdorffii em feridas cutâneas de equinos. Quatro feridas de 2 cm foram realizadas bilateralmente na região lombar de seis equinos e tratadas diariamente com: solução salina, veículo, creme EH 10% ou creme OR 10%. Diariamente foi efetuada a análise macroscópica das feridas e planimetria para mensurar a área da ferida. Em quatro períodos experimentais diferentes (3, 7, 14 e 21 dias), as biópsias foram realizadas e utilizadas para análises microscópicas. As análises microscópica e clínica indicaram melhor resposta cicatricial nas feridas tratadas com HE e OR em comparação com os controles. O grupo OR apresentou melhor qualidade de cicatrização, especificamente após sete dias de tratamento. Portanto, as formulações de Copaifera langsdorffii utilizadas apresentaram potencial de cicatrização de feridas em lesões de pele de cavalo, exibindo uma melhora nos parâmetros macro e microscópicos.Copaifera langsdorffii is a Brazilian native plant that is used for wound healing or as an anti-inflammatory agent. Non-healing wounds are an important health problem, particularly in horses, because they can cause the animal invalidity or even lead to death. In addition, horses respond to skin wounds with chronic inflammatory response and intense wound granulation, thereby delaying the healing process. By this way, our aim was to evaluate the healing potential of Copaifera langsdorffii hydroalcoholic extract (HE) and oil-resin creams (OR) in horse skin wounds. Four wounds were performed bilaterally in the lumbar region of six horses with a 2 cm punch and treated daily with the respective treatments: saline solution, vehicle, 10% HE creams or 10% OR cream. Daily planimetry analyses were performed to measure the wound area and clinical parameters. In four different experimental periods (3, 7, 14 and 21 d), wound biopsies were removed and used for microscopic analyses. SS wounds presented a significant small area at day 3 and 7, OR wounds presented significant small area in comparison with HE at 14 d, and no significant difference was observed between treatments at 21 d. A better microscopic and clinical healing activity of HE and OR was identified in comparison with the controls. The OR group showed better healing quality, specifically after 7 d of treatment. Therefore, Copaifera langsdorffii formulations demonstrated their wound healing potential in horse skin lesions, exhibiting an improvement of the macro- and microscopic parameters

Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae)

In this study, the antiulcerogenic effect of essential oil from Baccharis dracunculifolia was evaluated using the model of acute gastric lesions induced by ethanol. The ulcerative lesion index (ULI) was significantly reduced by oral administration of the essential oil of B. dracunculifolia at doses of 50, 250 and 500 mg/kg which reduced the lesions by 42.79, 45.70 and 61.61%, respectively. The analysis of the chemical composition of the essential oil from B. dracunculifolia by GC showed that this was composed mainly of mono- and sesquiterpenes and the majority compound was nerolidol. Therefore, antiulcerogenic activity of nerolidol (50, 250 and 500 mg/kg) was investigated using ethanol-, indomethacin- and stress-induced ulcer models in rat. In the stress-induced ulcer model, a significant reduction of the ULI in animals treated with nerolidol (50, 250 and 500 mg/kg) and cimetidine (100 mg/kg) was observed, compared to the control group (p < 0.05). The percentage of inhibition of ulcer was 41.22, 51.31, 56.57 and 53.50% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. Regarding ethanol- and indomethacin-induced ulcer models, it was observed that the treatment with nerolidol (250 and 500 mg/kg) significantly reduced the ULI in comparison with the control group (p < 0.05). The dose of 50 mg/kg reduced the parameters analyzed but this was not statistically significant. In the ethanol-induced model percentage of inhibition of ulcer was 34.20, 52.63, 87.63 and 50.87% in groups treated with 50, 250, 500 mg/kg of nerolidol and 30 mg/kg of omeprazol (positive control), respectively. In indomethacin-ulcer the percentage of inhibition of ulcer was 34.69, 40.80, 51.02 and 46.93% in groups treated with 50, 250, 500 mg/kg of nerolidol and 100 mg/kg of cimetidine (positive control), respectively. The results of this study show that nerolidol displays antiulcer activity, as it significantly inhibited the formation of ulcers induced in different animal models. However, further pharmacological and toxicological investigations, to delineate the mechanism(s) of action and the toxic effects, are required to allow the use of nerolidol for the treatment of gastric ulcer. © 2007 Verlag der Zeitschrift für Naturforschung

Copaifera langsdorffii: evaluation of potential gastroprotective of extract and isolated compounds obtained from leaves

AbstractGastric ulcer is a prevalent gastrointestinal disease, and the drugs currently used in the treatment produce several adverse effects. In this context, the search for new therapeutic antiulcer agents is essential, and medicinal plants have great potential. Here, we investigated the gastroprotective properties of Copaifera langsdorffii Desf., Fabaceae, hydroalcoholic extract obtained from leaves and its isolated compounds. The phytochemistry studies and the compounds isolations were performed using chromatographic and spectroscopic methodologies. The hydroalcoholic extract was evaluated using ethanol/HCl, non-steroidal anti-inflammatory drug, stress-induced-ulcer and chronic ulcer-model. The effects on gastric content volume, pH, total acidity and mucus stomach production were evaluated in the pylorus ligated-model. The C. langsdorffii extract obtained from leaves (50, 250 or 500 mg/kg) reduced the injured area compared to control group in all experiments. The extract showed a significant decrease in the total gastric juice acidity and an increase in mucus production (500 mg/kg) when compared to vehicle. Among isolated compounds (30 mg/kg) &#945;-humulene, &#946;-caryophyllene and caryophyllene oxide showed greater gastroprotective activity in the ethanol/HCl induced ulcer model. The data herein obtained shown that C. langsdorffii leaves extract and isolated compounds from it, presented gastroprotective properties in different animal models of gastric ulcer. These effects may be associated with the ability of the extract to decrease gastric secretion and increase the mucus production