Maytenus robusta Reissek, a medicinal plant popularly used to treat digestive diseases, promotes ameliorative effects in colon and liver of mice exposed to dextran sulfate sodium.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus robusta Reissek (Celesteraceae), popularly named as cafezinho do mato or coração de bugre, is employed to treat inflammatory digestive diseases in the south of Brazil. However, despite popular usage, the effects of this species on an experimental model of ulcerative colitis are unknown. AIM OF THE STUDY: To evaluate the effects of M. robusta extract (HEMR) on colon and liver from mice with colitis induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: Firstly, the cytotoxicity of HEMR and its effects on ROS and nitrite production in IEC-6 cells were evaluated. The experimental colitis was established by adding 3% DSS on drinking water of mice and the effects of HEMR (1-100 mg/kg, p.o, once a day by 7 days) in colonic and hepatic tissues were analyzed. RESULTS: The HEMR (1-100 µg/mL) did not alter the cell viability but reduced nitrite production of IEC-6 stimulated by LPS. Moreover, HEMR (100 mg/Kg) attenuates macro and microscopic alterations in the colon from mice exposed to DSS, as evidenced by a reduction of the colon shortening, attenuation of the epithelial erosion, submucosal edema and preservation of the Goblet cells integrity, as well as the restoration of mucin depletion. The treatment with HEMR increased GSH amount, reduced LOOH levels and normalizes CAT activity in the colon. The group treated with HEMR showed increased GST activity, reduced MPO activity and decreased inflammatory cytokines secretion (TNF and IL-6) in the colonic tissue. In the liver, HEMR increased GST activity, decreased the GPx activity and reduced IL-6 levels. Furthermore, the HEMR treatment reduced AST and ALT serum levels in mice exposed to DSS. Finally, the HEMR was able to reduce intestinal transit. CONCLUSIONS: HEMR treatment minimizes inflammation of the colon and maintaining the antioxidant homeostasis. In addition, HEMR may be a potential tool to prevent hepatic injury secondary to ulcerative colitis.

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.

Preclinical evaluation of the diuretic and saluretic effects of (-)-epicatechin and the result of its combination with standard diuretics.

Several studies have suggested that (-)-epicatechin-containing foods and plant extracts benefit conditions that affect the cardiovascular system, such as hypertension and endothelial dysfunction. However, no study was conducted so far to evaluate the potential of this flavonoid on diuretic activity assay. For that, female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics for clinical use, as well as with L-NAME, atropine and indomethacin were also explored. Cumulative urine volume, plasma and urinary parameters were evaluated at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3 mg/kg, EPI was able to stimulate both diuresis and saluresis (Na+, K+ and Cl-), without interfering with plasma electrolyte content or urinary pH and uric acid values, when compared with VEH-treated only rats. The combination with HCTZ, but not with furosemide or amiloride, successfully strengthened EPI-induced diuresis. This effect was not accompanied by a potentiation of the saluretic effects. On the other hand, when given EPI in combination with amiloride, a significant increase in Cl- excretion and maintenance of the potassium-sparing effects characteristic of this class of diuretics were detected. In addition, the diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action was significantly precluded in the presence of indomethacin, a cyclooxygenase inhibitor. In conclusion, this study shows the diuretic and saluretic properties of EPI in rats, adding another biological activity whose effect may contribute to the different positive actions already described.

Antioxidant and anti-inflammatory effect of plumieride in dextran sulfate sodium-induced colitis in mice.

This study aimed to investigate the potential effect of plumieride, an iridoid glycoside isolated from Alamanda cathartica L. flowers, against dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced in female swiss mice by adding DSS 3% to the drinking water. The animals were treated with vehicle (water), 5-aminosalicylic acid (100?mg/kg) or plumieride (10, 30 and 100?mg/kg) once a day, during 7 days. The body weight progression and the disease activity index was evaluated daily. On the eighth day, colons were collected for the measurement of the size, histological, histochemical, biochemical and inflammatory analysis. The cytotoxicity of plumieride on intestinal epithelial cell (IEC-6 cell line) was also evaluated. Plumieride, at dose of 100?mg/kg, significantly attenuated the mice weight loss, showed lower score in the disease activity index, diminished the colon shortening, improved the histological damage and avoided mucosa intestinal mucus depletion when compared with vehicle-treated only group. Moreover, plumieride was able to reduce the amount of colonic lipid hydroperoxides, while augmented reduced glutathione levels and superoxide dismutase activity. Although DSS intake stimulated an increase in myeloperoxidase activity and in tumor necrosis factor content on the colon tissue of the vehicle-treated group, the colons obtained from mice treated with plumieride did not present any of these changes. Taking together, the results of the present study disclose that plumieride exhibited a significant efficacy in attenuating the parameters of experimental ulcerative colitis, which may be mediated by an antioxidant and anti-inflammatory effect.

Essential oil of Cymbopogon citratus (lemongrass) and geraniol, but not citral, promote gastric healing activity in mice.

Cymbopogon citratus, popularly known as lemongrass, is used for the treatment of gastric, nervous and hypertensive disorders, in addition to its use in the food and pharmaceutical industries. This study evaluated the gastroprotective and gastric healing effect of essential oil of C. citratus (EOCC), citral and geraniol at doses of 1-100 mg/kg (p.o) on acute ethanol-induced ulcer and chronic acetic acid-induced ulcer. Histological and histochemical evaluation was also performed, as well as the in vitro evaluation of the effects of these phytochemicals on H+/K+-ATPase activity. In the ethanol-induced gastric ulcer, the minimum effective oral dose of EOCC, citral and geraniol were 10, 100 and 3 mg/kg, reducing the ulcer area by 51.67%, 96.57% and 55.74%, respectively, compared to vehicle group (25.82 ±â€¯3.59 mm2). Moreover, EOCC (10 mg/kg, p.o) and geraniol (3 mg/kg), but not citral (100 mg/kg), accelerated the gastric healing process by 34.52 and 80.57%, compared to acetic-acid ulcerated group treated with vehicle (36.04 ±â€¯1.03 mm2). These healing effects were confirmed histologically by the contraction of the ulcer base and by the enhancement on mucin staining in slices of ulcer site from mice treated with EOCC or geraniol. Interestingly, EOCC and citral at 100 µg/ml inhibited the H+/ K+-ATPase activity by 28.26% and 44.36%, whereas geraniol did not change this parameter. Together, these findings confirm the gastroprotective and healing gastric ulcer effects of essential oil from aerial parts of C. citratus and added the information that geraniol, but not citral, promotes healing effects on installed ulcers.

Prolonged diuretic and saluretic effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats: Role of antioxidant system and renal protection.

Although the acute diuretic effect of nothofagin has been recently demonstrated, its effects after dose-repeated treatment have not yet been explored. For that, male Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated, once a day, with vehicle (VEH: distilled water; 1 ml/kg), hydrochlorothiazide (HCTZ; 10 mg/kg) or nothofagin (NOT; 1 mg/kg). The cumulative diuretic index and urinary electrolytes excretion were measured each 24 h. On the last day of the experiment (7th day), urine, blood and kidney samples were collected for biochemical and molecular analyzes. The urinary volume of both NTR and SHR were significantly increased with the treatment with NOT (from the second to the seventh day of treatment), with final values reaching an increase of 56% and 82%, respectively, when compared with VEH-treated group. This effect was associated with increased levels of urinary excretion of Na+ and Cl-, without any changes on K+ excretion. None of the treatments modified urinary pH or density values. Importantly, neither the NOT nor the HCTZ caused any change in body weight following the dose-repeated treatment, and also did not provoke an electrolytic disturbance. Regarding the renal analyzes, when compared with the vehicle-treated NTR group, the activity of superoxide dismutase (SOD) and the reduced glutathione (GSH) levels in kidney homogenates of the SHR group were decreased, while the generation of lipid hydroperoxides were significantly increased. The daily treatment with NOT was able to restore the GSH levels and SOD activity, as well as reduced the lipoperoxidation in the kidney homogenates obtained from SHR animals. Finally, NOT significantly augmented the levels of nitrite, a marker of nitric oxide production, in the plasma obtained from SHR group when compared with the vehicle-treated only NTR. This study revealed the prolonged diuretic and saluretic effect of nothofagin in normotensive and hypertensive rats. Our data also showed the renal protective effects of nothofagin by the improvement of antioxidative capacity, as well as by the augmented bioavailability of plasma nitric oxide in the hypertensive group.

Phytochemical profile and gastroprotective potential of Myrcianthes pungens fruits and leaves

BACKGROUND: The last decade has been marked by increasing data regarding gastroinstestinal diseases, specially gastritis and ulcer. In order to prevent or treat these diseases, many studies have demonstrated the potential of medicinal plants. The aim of this study was to evaluate the phytochemical profile and the gastroprotective activity of the methanolic extract of Myrcianthes pungens whole fruit, peel, pulp, seeds, and leaves. METHODS: The methanolic extracts were analyzed by thin layer chromatography (TLC) to detect the presence of phenolic compounds by direct comparison with an authentic sample. To evaluate the gastroprotective activity, two experimental models were used: acute ulcer model induced by ethanol/HCl and acute ulcer model induced by nonsteroidal anti-inflammatory drug (indomethacin). Animals were divided in different groups (n= 6) and pretreated orally with the methanolic extracts of M. pungens at doses of 50, 125, and 250 mg/kg, the positive control (cimetidine 100 mg/kg) and negative control (distilled water).RESULTS: The TLC analysis indicated the presence of the flavonoids quercetin and quercitrin in the leaves, quercetinin the peel, and catechin and epicatechin in the leaves and seeds of M. pungens. The extracts of leaves, peel, and pulp showed significant gastroprotective potential regarding the relative area of the lesion observed only in acute ulcer model induced by ethanol. The extracts of whole fruit, peel, pulp, seeds, and leaves showed significant gastroprotective potential observed in acute ulcer induced by indomethacin model. CONCLUSIONS: The gastroprotective activity can be related with the presence of some phenolic compounds identified in phytochemical analysis.

Diuretic and natriuretic effect of luteolin in normotensive and hypertensive rats: Role of muscarinic acetylcholine receptors.

BACKGROUND: Luteolin is a very common phenolic compound found in a wide variety of natural products. Although several biological properties have already been described regarding the beneficial effect of luteolin in the cardiovascular and renal system, no scientific research explored its potential effect as a diuretic agent in experimental trials. METHODS: Groups of male normotensive (NTR) and spontaneously hypertensive rats (SHR) were orally treated with vehicle, hydrochlorothiazide or luteolin. In another experimental set, in order to verify the possible mechanisms of luteolin-induced diuresis, NTR were treated with vehicle, hydrochlorothiazide, amiloride, L-NAME, indomethacin or atropine, 1h before receiving luteolin. The cumulative urine volume, electrolytes excretion, pH and osmolality were measured at the end of the experiment (after 8h). RESULTS: Luteolin, at dose of 3mg/kg, was able to induce both diuretic and natriuretic effect in NTR and SHR groups, without interfering with urinary pH, K+ or Cl- levels. While Ca2+ content remained unchanged in urine from luteolin-treated group of NTR, luteolin reduced Ca2+ excretion in urine from SHR. The treatment with HCTZ and amiloride intensified luteolin-induced diuresis and natriuresis, with an interesting potassium-sparing effect, in addition to an increase in urinary osmolality levels. Moreover, the diuretic and natriuretic action of luteolin was fully avoided in the presence of atropine, a non-selective muscarinic receptor antagonist. CONCLUSIONS: This study revealed the diuretic and natriuretic effect of luteolin in normotensive and hypertensive rats. Our data also showed the involvement of muscarinic acetylcholine receptors for the renal effects of luteolin.

Influence of Prostanoids in the Diuretic and Natriuretic Effects of Extracts and Kaempferitrin from Bauhinia forficata Link Leaves in Rats.

Although Bauhinia forficata Link is popularly used in Brazil to induce diuresis, no scientific investigation has focused on demonstrating its efficacy in preclinical trials. For that, normotensive male Wistar and spontaneously hypertensive rats were used to test the effect of extracts and kaempferitrin obtained from Bauhinia forficata leaves in the experimental model of diuresis. Cumulative urine volume, Na+ and K+ excretion, calcium, creatinine, prostaglandin E2 , pH, density, and conductivity were measured at the end of the experiment (after 8 or 24 h). The treatment with aqueous infusion, methanolic extract, trichloromethane, or ethyl acetate-butanolic fractions significantly increase urinary volume and electrolytes levels when orally given to rats, without altering the pH or density parameters. Kaempferitrin induced diuretic, natriuretic, but not kaliuretic effects in both normotensive and hypertensive rats. In addition, kaempferitrin enhanced urinary creatinine and prostaglandin E2 excretion, without modifying calcium levels. Kaempferitrin-induced diuresis was unaffected by previous treatment with a nonselective inhibitor of nitric oxide synthase and neither with a nonselective muscarinic receptor antagonist. On the other hand, a cyclooxygenase inhibitor was able to decrease its effect when compared with vehicle-treated rats, suggesting that the diuretic and natriuretic properties from kaempferitrin are associated with endogenous prostanoids generation. Copyright © 2017 John Wiley & Sons, Ltd.

Screening of wild fruit trees with gastroprotective activity in different experimental models / Triagem de plantas frutíferas silvestres com ação gastroprotetora em modelos in vivo

ABSTRACT BACKGROUND Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. OBJECTIVE The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. METHODS The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. RESULTS The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. CONCLUSION It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.

RESUMO CONTEXTO Devido ao aumento de pessoas com distúrbios gastrointestinais, a busca de tratamentos alternativos com menos efeitos cola­terais é fundamental, assim como a demanda por alimentos ou plantas que possam ajudar a proteger o estômago. OBJETIVO O presente estudo teve como objetivo avaliar a ação gastroprotetora dos extratos plantas frutíferas silvestres Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) e Marlierea tomentosa Cambess. (guarapuruna) em modelos farmacológicos in vivo. MÉTODOS As diferentes partes do fruto foram submetidas se­paradamente a um processo de maceração em solução metanólica a frio. Foram realizados dois modelos experimentais em camundongos, modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl, que permitiram avaliar a atividade gastroprotetora dos extratos na dose de 250 mg/kg. Posteriormente, foram determinadas a área total de lesão (mm2) e a área relativa lesada (%). RESULTADOS Os resultados apresentaram atividade gastroprotetora significativa para todos os extratos estudados frente aos agentes agressores utilizados, etanol e indometacina. CONCLUSÃO Supõe-se que os frutos apresentam compostos bioativos, como as substancias antioxidantes, que atuam sobre os níveis de prostaglandinas, protegendo dos danos causados pelo etanol e indometacina. Os resultados encorajam futuros estudos para isolamento e identificação dos princípios ativos dos frutos.

Diuretic, natriuretic and potassium-sparing effect of nothofagin isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats.

Active constituents from natural origin have long been used for the treatment of patients suffering from cardiovascular and renal diseases. This study therefore aimed to investigate the diuretic and natriuretic properties of nothofagin, a dihydrochalcone isolated from Leandra dasytricha (A. Gray) Cogn. leaves in normotensive and hypertensive rats. Male Wistar normotensive rats were orally treated with vehicle (1 ml/kg); hydrochlorothiazide (HCTZ; 25 mg/kg); ethyl acetate fraction from L. dasytricha (EALD; 3-30 mg/kg) and nothofagin (NOT; 0.3-3 mg/kg). Spontaneously hypertensive rats (SHR) received NOT (1 mg/kg), HCTZ (25 mg/kg) or vehicle. The cumulative diuretic index, urinary electrolytes excretion (Na+ and K+), pH, density and conductivity were measured at the end of the experiment (after 8 h). A7r5 and L929 cell lines were used to measure cell viability after exposure to NOT. Nitric oxide generation was quantified in A7r5 cell supernatant, and DPPH assay was used for evaluating the antioxidant properties of NOT. The urinary volume of normotensive rats were increased after the treatment with EALD, without any changes in Na+ or K+ excretion. NOT was able to induce diuresis and natriuresis, but not kaliuresis, in both normotensive and hypertensive rats. The reduction in prostanoids generation through cyclooxygenase inhibition, as well as the muscarinic receptor antagonism, fully avoided NOT-induced increases in diuretic index. NOT, which did not interfere with L929 or A7r5 cell viability, was able to stimulate nitric oxide generation in A7r5 cell, besides showing an antioxidant effect in scavenging the free-radical DPPH. Taken together, our study shows, for the first time, the diuretic, natriuretic and potassium-sparing effect of nothofagin in rats, which was associated with prostanoids generation, muscarinic receptor activation and antioxidant properties.

SCREENING OF WILD FRUIT TREES WITH GASTROPROTECTIVE ACTIVITY IN DIFFERENT EXPERIMENTAL MODELS.

BACKGROUND: Given the increase of people with gastrointestinal disorders, the search for alternative treatments with fewer side effects is vital, as well as the demand for food or plants that can help protect the stomach. OBJECTIVE: The aim of this study was to evaluate the gastroprotective action of the extracts of wild fruit trees of Myrcianthes pungens (guabiju); Inga vera Willd. (ingá-banana) and Marlierea tomentosa Cambess. (guarapuruna) in in vivo pharmacological models. METHODS: The different parts of the fruits were separately subjected to a process of extraction by methanol. Two experimental pharmacological models were conducted in mice; the gastric ulcer model induced by non-steroidal anti-inflammatory (indomethacin), and the gastric ulcer model induced by ethanol/HCl, which allowed us to evaluate the gastroprotective activity of the extracts at a dose of 250 mg/kg. Subsequently, the total lesion area (mm2) and relative lesion area (%) were determined. RESULTS: The results showed significant gastroprotective activity against the aggressive agents used - ethanol and indomethacin - for all the extracts tested. CONCLUSION: It is assumed that the fruits have bioactive compounds such as antioxidant substances that act on the prostaglandin levels, protecting them from the damage caused by ethanol and indomethacin. These results prompt further studies to isolate and identify the active properties.

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.

In vivo evaluation of the genetic toxicity of Rubus niveus Thunb. (Rosaceae) extract and initial screening of its potential chemoprevention against doxorubicin-induced DNA damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined. MATERIALS AND METHODS: The animals were exposed to the extract for 24 and 48 h, and the doses selected were 500, 1000 and 2000 mg/kg b.w. administered by gavage alone or prior to DXR (30 mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH>13) comet assay and bone marrow micronucleus test. RESULTS AND CONCLUSION: The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p>0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000 mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR.

Dragon's blood Croton palanostigma induces genotoxic effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's blood is a dark-red sap produced by species from the genus Croton (Euphorbiaceae), which has been used as a famous traditional medicine since ancient times in many countries, with scarce data about its safe use in humans. In this research, we studied genotoxicity and clastogenicity of Croton palanostigma sap using the comet assay and micronucleus test in cells of mice submitted to acute treatment. MATERIAL AND METHODS: HPLC analysis was performed to identify the main components of the sap. The sap was administered by oral gavage at doses of 300 mg/kg, 1,000 mg/kg and 2,000 mg/kg. For the analysis, the comet assay was performed on the leukocytes and liver cells collected 24h after treatment, and the micronucleus test (MN) on bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). RESULTS AND CONCLUSION: The alkaloid taspine was the main compound indentified in the crude sap of Croton palanostigma. The results of the genotoxicity assessment show that all sap doses tested produced genotoxic effects in leukocytes and liver cells and also produced clastogenic/aneugenic effects in bone marrow cells of mice at the two higher doses tested. The PCE/NCE ratio indicated no cytotoxicity. The data obtained suggest caution in the use of Croton palanostigma sap by humans considering its risk of carcinogenesis.

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.

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.

Evaluation of the in vivo mutagenic potential of hydroalcoholic extracts of the northern highbush blueberry (Vaccinium corymbosum L. Ericales, Ericaceae) on peripheral blood cells of Swiss mice (Mus musculus Rodentia, Muridae)

The northern highbush blueberry (Vaccinium corymbosum L. Ericales, Ericaceae) is very rich in anthocyanins, natural pigments which have strong antioxidant properties and potential health benefits, resulting in the worldwide use the blueberry as a medicinal plant. We investigated the mutagenic potential of simple hydroalcoholic extracts of V. corymbosum acutely administrated by gavage to Swiss mice at doses of 1 g kg-1, 1.5 g kg-1 and 2 g kg-1. Peripheral blood cells were collected 4 h and 24 h post-gavage and assessed by the alkaline comet assay, with further blood samples being collected at 48 h and 72 h for assessment using the micronucleus (MN) assay. Our results show that the V. corymbosum extracts did not induce any statistically significant increase in the average amount of DNA damage in peripheral blood leukocytes. However, we did record a significant increase in the frequency of micronucleated polychromatic erythrocytes at the three doses tested.