In vivo study of anti-inflammatory and antinociceptive activities of Copaifera pubiflora Benth oleoresin.

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.

Antinociceptive and anti-inflammatory activities of Copaifera pubiflora Benth oleoresin and its major metabolite ent-hardwickiic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaifera species folkloric names are "copaíbas, copaibeiras, copaívas or oil stick", which are widely used in Brazilian folk medicine. Among all ethnopharmacological applications described for Copaifera spp oleoresins, their anti-inflammatory effect stands out. However, the knowledge of anti-inflammatory and antinociceptive properties of Copaifera pubiflora Benth is scarce. AIM OF THE STUDY: To investigate the cytotoxic, anti-inflammatory, and antinociceptive activities of C. pubiflora oleoresin (CPO), and its major compound ent-hardwickiic acid (HA). MATERIAL AND METHODS: The phosphatase assay was used to evaluate the cytotoxicity of CPO and HA in three different cell lines. CPO and HA doses of 1, 3, and 10 mg/kg were employed in the biological assays. The assessment of motor activity was performed using open-field and rotarod tests. Anti-inflammatory activity of CPO and HA was assessed through luciferase assay, measurement of INF-γ, IL-1ß, IL-6, IL-10, and TNF-α in a multi-spot system with the immortalized cell line THP-1, zymosan-induced arthritis, and carrageenan-induced paw edema. Acetic acid-induced abdominal writhing and formalin tests were undertaken to evaluate the antinociceptive potential of CPO and HA. In addition, the evaluation using carrageenan was performed to investigate the effect of CPO in pain intensity to a mechanical stimulus (mechanical hyperalgesia), using the von Frey filaments. A tail-flick test was used to evaluate possible central CPO and HA actions. RESULTS: In the cytotoxicity evaluation, CPO and HA were not cytotoxic to the cell lines tested. CPO and HA (10 mg/kg) did not affect animals' locomotor capacity in both open-field and rotarod tests. In the luciferase assay, CPO and HA significantly reduced luciferase activity (p < 0.05). This reduction indicates a decrease in NF-κB activity. HA and CPO decreased INF-γ, IL-1ß, IL-6, IL-10, and TNF-α at 24 and 72 h in the multi-spot system. In zymosan-induced arthritis, CPO and HA decreased the number of neutrophils in the joint of arthritic mice and the number of total leukocytes (p < 0.05). In experimental arthritis HA significantly decreased joint swelling (p < 0.05). CPO and HA also increased the mechanical threshold during experimental arthritis. HA and CPO significantly inhibited the carrageenan-induced paw edema, being the doses of 10 mg/kg the most effective, registering maximum inhibitions of 58 ± 8% and 76 ± 6% respectively, p < 0.05. CPO and HA reduced the nociceptive behavior in both phases of formalin at all tested doses. The highest doses tested displayed inhibitions of 87 ± 1% and 72 ± 4%, respectively, p < 0.001, in the first phase, and 87 ± 1% and 81 ± 2%, respectively, p < 0.001, in the second phase. Oral treatment of CPO and HA (1, 3, 10 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhings, and the 10 mg/kg dose was the most effective with maximum inhibitions of 86 ± 2% and 82 ± 1%, respectively, p < 0.001. Both HA and CPO significantly decreased the intensity of mechanical inflammatory hyper-nociception on carrageenan-induced hyperalgesia at all tested doses, and 10 mg/kg was the most effective dose with maximum inhibitions of 73 ± 5% and 74 ± 7%, respectively, p < 0.05.CPO increased the tail-flick latencies in mice, and concomitant administration of naloxone partially reduced its effect. CONCLUSIONS: CPO and HA may inhibit the production of inflammatory cytokines by suppressing the NF-κB signaling pathway, resulting in anti-inflammatory and antinociceptive activities.

Reliable Methods for Analyses of Volatile Compounds of Copaifera Oleoresins Combining Headspace and Gas Chromatography.

Two analytical methods were developed in this study for direct and fast chemical investigation of authentic Copaifera oleoresins (COR) and commercial products. Polydimethylsiloxane microfiber coupled to gas chromatography-mass spectrometry (HS-SPME-GC/MS) showed the best results for oleoresin qualitative analysis, setting the following extraction conditions: equilibrium time of 15 min, extraction time of 30 min, extraction temperature at 60 °C and constant stirring of 400 rpm. Sesquiterpenes α-copaene, ß-elemene, ß-caryophyllene and trans-α-bergamotene were found in all investigated samples. Quantitative analysis by gas chromatography coupled with flame ionization detector (GC-FID) measured the content of the four sesquiterpenes in all samples. Qualitative and quantitative results showed important differences between COR of distinct species and commercial products. Data regarding the volatile composition of C. oblongifolia and C. trapezifolia oleoresins were first presented in this study and two new analytical methods were reported for direct and fast qualitative and quantitative analysis of COR.

Experimental skin wound treatment with Copaifera langsdorffii Desf Kuntze (Leguminosae) extract and oil-resin in horses / Tratamento experimental de feridas cutâneas com extrato e óleo resina de Copaifera langsdorffii Desf Kuntze (Leguminosae) em equinos

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.(AU)

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 langsdorffiiutilizadas apresentaram potencial de cicatrização de feridas em lesões de pele de cavalo, exibindo uma melhora nos parâmetros macro e microscópicos.(AU)

Artepillin C, drupanin, aromadendrin-4'-O-methyl-ether and kaempferide from Brazilian green propolis promote gastroprotective action by diversified mode of action.

ETHOPHARMACOLOGICAL RELEVANCE: The propolis is extensively used in folk medicine in natura or to prepare pharmaceutical formulations since ancient time to improve health or prevent diseases, among them gastrointestinal disorders. Aiming to contribute in the scientific validation about the popular use of Brazilian Green propolis (BGP) against gastritis and gastric ulcer, this work evaluated the antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4-hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3), aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). MATERIAL AND METHODS: The compounds were characterized by nuclear magnetic resonance and mass spectrometry. Their gastroprotective effects were evaluated against ethanol/HCl- and indomethacin-induced ulcer in mice. Further, histological, histochemical, oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid antisecretory activities also were also assessed. RESULTS: Compound 2 did not reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg, respectively. Besides, these compounds prevented ethanol/HCl-induced ulcer by intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The gastroprotection was accompanied by normalization of superoxide dismutase, catalase and glutathione-S-transferase activities and reduction in myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased volume, pH, total acidity and pepsin activity of the gastric juice from rats. CONCLUSIONS: Together, our findings showed a diversified mode of action elicited by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer activity reported for BGP.

Skin Wound Healing Potential and Mechanisms of the Hydroalcoholic Extract of Leaves and Oleoresin of Copaifera langsdorffii Desf. Kuntze in Rats.

The wound healing is a complex process which, sometimes, can be a problem in public health because of the possibility of physical disability or even death. Due to the lack of a gold standard drug in skin wound treatment and aiming at the discovery of new treatments in skin repair and the mechanisms involved in the process, we used oleoresin (OR) from Copaifera langsdorffii and hydroalcoholic extract of the leaves (EH) to treat rat skin wounds. For that, male Wistar rats were divided into groups (n = 8): Lanette, Collagenase, 10% EH, or 10% OR and, after anesthesia, one wound of 2 cm was made in the back of animals. The wounds were treated once a day for 3, 7, or 14 days and the wound areas were measured. The rats were euthanized and skin samples destined to biochemical, molecular, and immunohistochemical analysis. The results showed a macroscopic retraction of the wounds of 10% EH and 10% OR creams and both treatments showed anti-inflammatory activity. Molecular and immunohistochemical results demonstrated the activity of Copaifera langsdorffii creams in angiogenesis, reepithelialization, wound retraction, and remodeling mechanisms.

Galloylquinic acid derivatives from Copaifera langsdorffii leaves display gastroprotective activity.

Nine new methylated galloylquinic acids were isolated from an aqueous fraction of Copaifera langsdorffii (Fabaceae-Caesalpinioideae) leaf hydroalcoholic extract (3-8, 11, 12, and 14), along with three known methylated galloylquinic acids (1, 2, and 15) and four galloylquinic acids (9, 10, 13, and 16). These compounds were characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. They were further tested in a gastroprotection assay (Ethanol-HCl induced ulcer model in mice), in which all of them significantly reduced the total lesion area, and increased the cure ratio in comparison with pantoprazole. Also, the tested compounds displayed cytotoxicity against gastric adenocarcinoma cells.

Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as "panaceia". Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. AIM OF THE STUDY: To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. MATERIAL AND METHODS: The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti-Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. RESULTS: The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. CONCLUSIONS: The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract.

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) α-humulene, β-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.

Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice.

OBJECTIVES: This study has aimed to assess the mechanisms of action for the gastroprotective effect of the acetone extract (PCAE) and methanol fraction (PCMF) of Polygala cyparissias, as well as to evaluate the activity of 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (1), 1,7-dihydroxy-2,3-dimethoxyxanthone (2) and astragalin (3). METHODS: Gastric secretion and mucus content were determined by pylorus ligation in mice. Nitric oxide (NO) and sulfhydryl group participation were observed by the pretreatment of mice with L-NAME or NEM. Acute ulcer was induced by ethanol/HCl and chronic ulcer by acetic acid. Anti-Helicobacter pylori activity was evaluated by the agar solid dilution assay. KEY FINDINGS: Neither PCAE nor PCMF had the ability to reduce H(+) concentration. However, both of them enhanced mucus secretion. PCAE demonstrated its gastroprotection in a NO-dependent manner, while PCMF exerted the activity depending on the sulfhydryl group. In chronic ulcer, the curative ratios for the PCAE and PCMF were 67.5 and 58.4%, respectively. No effect over H. pylori was detected. Compounds 1, 2 and 3 were able to reduce lesions in the order of 79.6, 73.8 and 67.6%, respectively. CONCLUSIONS: The data suggested that PCAE and PCMF displayed antiulcer activity due to different mechanisms and with the participation of phenolic compounds obtained from the plant.

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.

Gastroprotective activity of hydroalcoholic extract obtained from the leaves of Brassica oleracea var. acephala DC in different animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Brassica oleracea var. acephala DC has been extensively used in Brazilian traditional medicine to treat gastric ulcer. AIM OF THE STUDY: This study was conducted to evaluate the antiulcerogenic property of hydroalcoholic extract obtained from the leaves of Brassica oleracea. MATERIALS AND METHODS: Antiulcer assays were performed using the protocol of ulcer induced by ethanol/HCl, and non-steroidal anti-inflammatory drugs (NSAIDs). Parameters of gastric secretion (volume, pH and [H(+)]) were determined by the pylorus ligation model and mucus in gastric contents. RESULTS: In the ethanol-induced ulcer model, we observed a significant reduction in all the parameters analyzed, obtaining curative ratios of 58.8 ± 11.5, 86.2 ± 12.2 and 42.8 ± 6.6% for the groups treated with 50 and 100mg/kg of extract and omeprazole (30 mg/kg), respectively. The dose of 25mg/kg of hydroalcoholic extract of Brassica oleracea showed no significant results. In the indomethacin-induced ulcer, the percentages of ulcer inhibition were 64.3 ± 9.9, 66.4 ± 12.3 and 81.2 ± 7.5% for the groups treated with 50 and 100mg/kg extract and positive control (cimetidine, 100mg/kg), respectively. The results showed a significant increase in pH and mucus production in the groups treated with Brassica oleracea when compared with the control group. No sign of toxicity was observed in the acute toxicity study. CONCLUSIONS: The results of the present study show that hydroalcoholic extract of Brassica oleracea displays antiulcer activity, as demonstrated by the significant inhibition of ulcer formation induced using different models. The data suggest that the effectiveness of the extract is based on its ability to stimulate the synthesis of mucus, increase pH and decrease H(+) ions in the stomach. This work corroborates the ethnopharmacology use of Brassica oleracea preparations, contributing to its pharmacological validation by suggesting that preparations obtained from Brassica oleracea could be used for the development of new phytopharmaceuticals for the treatment of gastric ulcer.

Gastroprotective activity of methanol extract and marrubiin obtained from leaves of Marrubium vulgare L. (Lamiaceae).

OBJECTIVES: The purpose of this study was to assess the gastroprotective properties of the methanol extract and the diterpene marrubiin obtained from the leaves of M. vulgare. METHODS: Assays were performed using different protocols in mice. Studies focusing on mechanisms of gastroprotection were also undertaken. KEY FINDINGS: In the model of ethanol-induced ulcers, we observed a significant reduction in all the parameters analysed; the curative ratios obtained were 49.31±0.57, 74.31±0.91 and 79.86±0.59 for the groups treated with 50 and 100mg/kg of extract of M. vulgare and omeprazole (30mg/kg), respectively. For indomethacin-induced ulcers, the percentages of ulcer inhibition were 50.32±5.60, 66.24±4.30, 82.17±04.09 and 67.52±4.38, for the groups treated with 25, 50 and 100mg/kg M. vulgare and positive control (cimetidine), respectively. In both models, the marrubiin (25mg/kg) produced a significant reduction in all the parameters when compared with the control group (P<0.01). There was also a significant increase in pH and mucus production in the groups treated with M. vulgare extract and marubiin. The results also demonstrated that the gastroprotection induced by the extract and marubiin is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. CONCLUSIONS: The results of this study show that the extract of M. vulgare and marrubiin displays antiulcer activity and that this effect can be partly attributed to the isolated diterpene.

Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models.

Syzygium aromaticum, a medicinal plant commonly known as clove, is used to treat toothache, respiratory disorders, inflammation, and gastrointestinal disorders. From the flower buds of S. aromaticum, it is possible to obtain an essential oil comprised of a mixture of aliphatic and cyclic volatile terpenes and phenylpropanoids, being eugenol as the main component. The aims of this study were: (1) to extract the essential oil of the flower buds of S. aromaticum, (2) to identify and quantify the main component of the essential oil, and (3) to evaluate its antiulcer activity using different animal models. Assays were performed using the following protocols in rats: indomethacin-induced and ethanol/HCl-induced ulcer model. Both essential oils from S. aromaticum and eugenol displayed antiulcer activities in the rat models of indomethacin- and ethanol-induced ulcer. Studies focusing on the possible mechanisms of gastroprotection were also undertaken using the following experiments: evaluation of gastric secretion by the pylorus-ligated model, determination of mucus in gastric content, participation of nitric oxide (NO) and endogenous sulfhydryl in gastric protection. The results show that there was no significant effect on the volume of gastric juice and total acidity. However, the quantification of free gastric mucus showed that the clove oil and eugenol were capable of significantly enhancing mucus production. With regard to the NO and endogenous sulfhydryls, the results demonstrated that the gastroprotection induced by clove oil and eugenol are not related to the activities of the nitric oxide and endogenous sulfhydryls. No sign of toxicity was observed in the acute toxicity study. In conclusion, the results of this study show that essential oil of S. aromaticum, as well as its main component (eugenol), possesses antiulcer activity. The data suggest that the effectiveness of the essential oil and eugenol is based on its ability to stimulate the synthesis of mucus, an important gastroprotective factor. However, further pharmacological and toxicological investigations are required to enable its use for the treatment of gastric ulcer.

Antiulcer effects of Achyrocline satureoides (Lam.) DC (Asteraceae) (Marcela), a folk medicine plant, in different experimental models.

ETHNOPHARMACOLOGICAL RELEVANCE: Achyrocline satureoides is a medium-sized South American indigenous herb, commonly known as "Marcela" or "Macela". The infusion obtained from inflorescences of this plant is widely used in Brazilian folk medicine as an antispasmodic, anti-inflammatory, hypoglycemic, and hypocholesterolemic, mainly to treat gastrointestinal disorders such as gastric ulcers and dyspepsia. However, the antiulcer properties of this species have not yet been fully studied. AIM OF THE STUDY: This study was conducted to evaluate and contribute to validating the antiulcer activity of hydroalcoholic extract of inflorescences of Achyrocline satureoides. MATERIALS AND METHODS: The antiulcer assays were performed using the ethanol-induced ulcer, and nonsteroidal anti-inflammatory drug (NSAID)-induced ulcer protocols. Gastric secretion parameters were also evaluated (volume, pH and total acidity) by the pylorus ligated model, and the mucus in the gastric content was determined. RESULTS: In the ethanol-induced ulcer model, it was observed that the treatment with Achyrocline satureoides extract significantly reduced the lesion index by 75.1+/-8.6, 85.0+/-9.2, 86.6+/-7.4 and 75.5+/-5.3 for the groups treated with 100, 250 and 500 mg/kg of extract of inflorescences of Achyrocline satureoides and the positive control (omeprazole 30 mg/kg), respectively. Significant inhibition was also observed in the lesion index in the indomethacin-induced ulcer model, with decreases of 62.5+/-7.1, 62.5+/-6.1, 63.6+/-5.5 and 96.2+/-3.6 for the groups treated with 100, 250 and 500 mg/kg of extract and the positive control (cimetidine 100 mg/kg), respectively. The parameters of gastric secretion (pH, volume, [H(+)]) showed no alteration in the different doses of the treatment. On the other hand the treatment with the hydroalcoholic extract of Achyrocline satureoides (100, 250 and 500 mg/kg), significantly increased mucus production (p<0.01), when compared with the groups treated with indomethacin (100 mg/kg), cimetidine (100 mg/kg) and negative control (vehicle). No signs of toxicity was observed in the acute toxicity study. CONCLUSIONS: The results of the present study show that hydroalcoholic extract of Achyrocline satureoides displays antiulcer activity, as demonstrated by the significant inhibition of the formation of ulcers induced using different models. However, this activity appears not be related to the antisecretor mechanisms. Moreover, this work suggests that preparations obtained from Achyrocline satureoides could be used for the development of new phytotherapic drugs for the treatment of gastric ulcer.

Antiulcerogenic activity of extract, fractions, and some compounds obtained from Polygala cyparissias St. Hillaire & Moquin (Polygalaceae).

The present study evaluates the gastroprotective properties of acetone extract, chloroform, and methanol fractions, alpha-spinasterol (1); 1,3-dihydroxy-7-methoxyxanthone (2); and 1,7-dihydroxy-2,3-methylenedioxyxanthone (3) obtained from Polygala cyparissias (Polygalaceae). Gastroprotective assays were performed in mice using ethanol/HCl and nonsteroidal anti-inflammatory drug (NSAID)/bethanechol-induced ulcer models. Chloroformic fraction showed no interesting results. On the other hand, in the ethanol/HCl-induced ulcer model, the treatment using doses of 50, 125, and 250 mg/kg promoted ulcer inhibition of 45.19+/-12.93%, 62.99+/-3.49%, and 67.40+/-4.75% for acetone extract and 43.70+/-5.12%, 64.56+/-5.64%, and 74.49+/-6.13% for methanol fraction. In the model of NSAID/bethanechol-induced ulcer, the ulcer inhibitions in the same doses were 28.12+/-12.45%, 60.16+/-6.58%, and 77.86+/-7.18% for the acetone extract and 46.09+/-6.92%, 67.45+/-4.36%, and 75.00+/-2.92% for the methanol fraction. In view of the antiulcer potential of the acetone extract and its high yield and xanthone content, it was submitted to chromatographic procedures, giving compounds 1-3, which were also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, these compounds reduced the percentage of ulcer by around 71.26+/-9.40%, 81.10+/-5.75%, and 86.22+/-3.42%, for compounds 1, 2, and 3, respectively. The antiulcerogenic activity of P. cyparissias may be attributed, at least in part, to these compounds.

Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae).

As part of our continuing search for bioactive natural products from plants, the present study was carried out in order to evaluate the gastroprotective properties of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora (Rutaceae). Anti-ulcer assays were performed using the following protocols in mice: nonsteroidal anti-inflammatory drug (NSAID)/bethanecol-induced ulcer, ethanol/HCl-induced ulcer, and stress-induced ulcer. The effects of the extract on gastric content volume, pH and total acidity were also evaluated, using the pylorus ligated model. Treatment using doses of 50, 125 and 250 mg/kg of G. longiflora alkaloid extract and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, total lesion area, and percentage of lesion, in comparison with the negative control groups in all the models evaluated. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in gastric pH. The main alkaloid of the plant, 2-phenylquinoline, was also evaluated in the ethanol-induced ulcer model. The results showed that at a dose of 50 mg/kg, it significantly inhibited ulcerative lesions. However, this effect was less than that of the alkaloid extract. All these results taken together show that G. longiflora displays gastroprotective activity, as evidenced by its significant inhibition of the formation of ulcers induced by different models. There are indications that mechanisms involved in anti-ulcer activity are related to a decrease in gastric secretion and an increase in gastric mucus content. Also, there is evidence of involvement of NO in the gastroprotector mechanisms. These effects may be attributed, at least in part, to the presence of some alkaloids, particularly 2-phenylquinoline.

Antiulcerogenic activity of the essential oil of Baccharis dracunculifolia on different experimental models in rats.

Baccharis dracunculifolia DC (Asteraceae), a native plant from Brazil, commonly known as 'Alecrimdo-campo' is widely used in folk medicine to treat inflammation, hepatic disorders and stomach ulcers, and it is the most important botanical source of Southeastern Brazilian propolis, known as green propolis. Its essential oil is composed of non-oxygenated and oxygenated terpenes. In this work, the effects of the essential oil obtained from the aerial parts of B. dracunculifolia on gastric ulcers were evaluated. The antiulcer assays were undertaken using the following protocols in rats: nonsteroidal antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, stress-induced ulcer, and determination of gastric secretion using ligated pylorus. The treatment in the doses of 50, 250 and 500 mg/kg of B. dracunculifolia essential oil significantly diminished the lesion index, the total lesion area and the percentage of lesions in comparison with both positive and negative control groups. With regard to the model of gastric secretion a reduction of gastric juice volume and total acidity was observed, as well as an increase in the gastric pH. No sign of toxicity was observed in the acute toxicity study. Considering the results, it is suggested that the essential oil of B. dracunculifolia could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer.

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis.

AIM OF THE STUDY: In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis. MATERIAL AND METHODS: The anti-ulcer assays were performed using the following protocols: nonsteroidal-antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated. RESULTS: It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastric juice and total acidity and significantly increased the gastric pH (p<0.05), compared with the control group, with the exception of the group treated with 50mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2,000 mg/kg. CONCLUSIONS: In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity.

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.