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Qualea grandiflora is one of the species widely used in folk medicine to treat gastric ulcers in Cerrado of the central region of Brazil. The hydroalcoholic extract of bark (HE) of Qualea grandiflora was investigated for their ability to prevent and heal lesions in the gastric mucosa. The oral administration of HE exhibited antiulcer activity decreasing the ulcerative index induced by HCl/ethanol solution, indomethacin/bethanechol and stress. In the Shay model, results showed that HE (p.o.) only reduced the severity of gastric lesions without effects on pH, gastric acidity or volume. When given by intraduodenal route, HE changed the pH, but did not modify the other parameters of the gastric juice. These data were in accordance with those obtained when HE was administered orally for 14 days after gastric ulcers were induced by acetic acid in rats. HE presented healing process in subacute gastric ulcer induced by acetic acid in rats. Moreover, histological examinations showed the simple columnar epithelium, lamina propria with simple branched tubular glandules with dilated lumen and large amounts of mucus secretion. Phytochemical investigation of HE led to the detection of terpenes, steroids, saponins, phenolic compounds and tannins in this extract, which may be involved in the observed activity. [ABSTRACT FROM AUTHOR]

ETHNOPHARMACOLOGICAL RELEVANCE: Qualea parviflora Mart. is a medicinal species commonly found in the Brazilian Cerrado biome. AIM OF THE STUDY: Based on ethnopharmacological data, methanolic extract from Qualea parviflora (QP) bark was evaluated for its antiulcer, analgesic, anti-hemorrhagic, mutagenic and anti-Helicobacter pylori activities. MATERIAL AND METHODS: The gastroprotective action of the extract was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated mutagenic effect (Ames assay), anti-Helicobacter pylori, anti-hemorrhagic action, analgesic and inflammatory effects (hot-plate test and carrageenin-induced hind paw edema) of methanolic extract from Qualea parviflora. RESULTS: QP (500 mg/kg, p.o.) was able to protect gastric mucosa against HCl/ethanol solution (77%), absolute ethanol (97%), and also against injurious effect of NSAID (36%). When QP was challenged with sulfhydryl depletor compound, the gastroprotective action of extract was abolished. QP treatment was able to maintain the GSH level and show a concentration-dependent inhibition effect on the lipid peroxidation. QP present anti-Helicobacter pylori effect (MIC=75 microg/mL), anti-hemorrhagic and antidiarrheal action but not present analgesic or anti-inflammatory effect. CONCLUSION: methanolic extract from Qualea parviflora had gastroprotective effect related to the increase of gastric mucosa defensive factors such PGE(2) levels and maintain the basal gastric glutathione levels. The methanolic extract also showed anti-Helicobacter pylori activity, anti-hemorrhagic effect and antioxidant action, but absence of analgesic, mutagenic and toxic effects, a profile that adds safety to its use. [ABSTRACT FROM AUTHOR]

ETHNOPHARMACOLOGICAL RELEVANCE: Cordia verbenacea is a medicinal plant popularly used in Brazil as anti-inflammatory, antiulcer and anti-rheumatic agent without detailed pharmacological and toxicological studies. AIM OF THE STUDY: The study was aimed to investigate the effects of Cordia verbenacea in antiulcer, analgesic and antioxidant assays, as well as to evaluate its toxic effects and phytochemical profile. MATERIAL AND METHODS: Antiulcer activity of plant extract was evaluated using ethanol/HCl, ethanol and piroxican-induced gastric lesions methods. The pH, volume and total acid of gastric juice were determined by pylorus-ligated assay. Analgesic activity was evaluated by writhing, tail-flick and hot-plate tests. Antioxidant activity was determined by in vitro lipoperoxidation assay. Acute toxicity and number of deaths were evaluated by Hippocratic screening. RESULTS: The ethanol leaf extract shows a potent antiulcer activity in the ethanol/HCl and absolute ethanol-induced gastric lesions. The IC(50) value of plant extract on the lipid peroxidation was 76.11mug/ml. Preliminary phytochemical tests were positive for flavonoids, steroids, saponins, fixed acids, alkaloids and phenols. In the analgesic models the extract did not present any activity. CONCLUSIONS: Cordial verbenaceae showed a potent antiulcer activity at the dose of 125mg/kg and this effect may be associated with an improvement in stomach antioxidant mechanisms. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Baccharis trimera (Less.) DC known as "carqueja" in Brazil has been acknowledged as a medicinal plant in folk medicine for the treatment of stomach aches and gastrointestinal disorders., Aim of the Study: The present study aimed to evaluate the gastroprotective and healing effects of essential oil from B. trimera (EOBT) against gastric ulcer lesions caused by absolute ethanol and acetic acid, respectively, and to identify the mechanism of action of this essential oil in male Wistar rats., Materials and Methods: The plant material used to obtain EOBT was collected in the southern region of Brazil and was analyzed by chromatography-mass spectrometry (GCMS) demonstrate its characteristic chemical composition, with carquejyl acetate as its main component. Different doses of EOBT (50, 100, and 200 mg/kg) were administered orally in male Wistar rats as an acute treatment against absolute ethanol-induced gastric lesions. The gastric healing effect of EOBT (100 mg/kg) was evaluated once a day after 7, 10, and 14 days of treatment. After treatment, the stomachs of rats from all groups were collected to measure the lesion area (mm 2 ), the activity of myeloperoxidase (MPO), and the relative expression of caspases -3, -8, -9, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). The zymography method was used to elucidate the activity of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in the healing action of EOBT. We also analyzed toxicological parameters (body weight evolution and biochemical parameters) that could result after treatment with this essential oil for 14 days., Results: Pretreatment with EOBT (100 and 200 mg/kg) significantly decreased the severity of gastric damage induced by absolute ethanol and decreased MPO activity in gastric tissue. After 10 and 14 days of treatment with EOBT (100 mg/kg) once a day, the lesion area was significantly reduced by 61% and 65.5%, respectively, compared to the negative control group. The gastric healing effect of EOBT was followed by a decrease in the expression of COX-1 compared to that in the negative control group. Notably, treatment with EOBT for 14 days increased the expression of VEGF compared to that using an anti-ulcer drug (lansoprazole). Additionally, analyses of MMP-2 and MMP-9 activities in the gastric mucosa confirmed the accelerated gastric healing effect of EOBT, with a significant decrease in the activity of pro-MMP-2. No sign of toxicity was observed after treatment with EOBT for 14 consecutive days., Conclusion: These findings indicated that EOBT was effective in preventing and accelerating ulcer healing by decreasing MPO activity, increasing VEGF expression, and decreasing MMP-2 activity. These actions collectively contribute to the rapid recovery of gastric mucosa following treatment with EOBT, without any observed toxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Terminalia catappa L. (Combretaceae), known as "amendoeira da praia" in Brazil, has been recognized as a medicinal plant in folk medicine for the treatment of gastrointestinal disorders and other inflammatory conditions. The present study aimed to investigate the preventive and healing effects of the infusion of leaves of T. catappa (ILTC) against gastric lesions caused by ischemia and reperfusion (I/R) injury and characterize its mechanism of action in the gastric mucosa of rats., Materials and Methods: Different doses (30, 100, and 300 mg/kg) of ILTC were orally administered as acute and subacute treatments against I/R-induced gastric lesion in rats. After treatment, the stomach of rats was collected to measure the lesion area, redox parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) and inflammatory parameters myeloperoxidase activity (MPO), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). The activities of matrix metalloproteinases 2 and 9 (MMPs 2 and 9) were assessed by zymography method to clarify the mechanisms of the healing acceleration promoted by ILTC., Results: Pretreatment with ILTC (100 mg/kg) was effective in preventing the aggravation of lesions in the acute model by reducing MPO activity by 38% relative to control group, despite the lack of clarity of this action at the macroscopical level at the lesion area (p < 0.05). After three days of treatment with ILTC (30 and 100 mg/kg), this infusion significantly reduced the lesion area by 95% and 89%, respectively, compared the control (p < 0.05). The gastric healing effect of all doses of ILTC was followed by a reduction in MPO activity (decrease by 70-78%). Compared to the negative control, an improvement in gastric healing owing to treatment with ILTC was observed and this was followed by an increase in MMP-2 (20-47%) (p < 0.05)., Conclusion: Three days of treatment with ILTC could accelerate the healing process in I/R-induced lesions in rats. By decreasing MPO levels, ILTC enabled the action of MMP-2, which led to tissue recovery in the gastric mucosa., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Eugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as "pedra-ume-caá," is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol., Materials and Methods: The healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm 2 ), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters., Results: Macroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (p < 0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (p > 0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (p < 0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (p < 0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (p < 0.05)., Conclusion: These findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Alibertia edulis, popularly known as "marmelo do Cerrado" is a native plant from the brazilian Cerrado. It has high food and ornamental potential and the tea leaves are currently used as hypoglycemic, antihypertensive and diuretic., Aim of the Study: In order to evaluate the safety of the aqueous extract of Alibertia edulis leaves (AEAE), the acute and subacute toxicity tests were performed in male and female Wistar albino rats., Materials and Methods: The experiments were performed in accordance with the OECD guidelines 425 and 407. For the acute toxicity, one single dose of the AEAE (2000mg/kg) was administered by gavage to five female rats. The animals were observed for 14 days for any signs of toxicity and death. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the AEAE were administered to male and female rats for 28 consecutive days. A satellite group received the maximum dose (1000mg/kg) for 28 days and remained untreated for 14 more days in order to observe reversibility, persistence, or delayed occurrence of toxic effects. The five parameters of the Hippocratic screening, body weight, food and water intake were daily observed. At the end of the experiment, blood samples were collected for the hematological and biochemical analysis. The vital and reproductive organs were inspected for any histopathological changes., Results: No deaths or behavioral changes were observed during both experiments as well as no changes on organ weights, biochemical, hematological and histopathological parameters that could indicate any signs of toxicity., Conclusion: All doses tested can be considered safe in rats and the LD 50 is higher than 2000mg/kg. Therefore, further assessments are required in order to proceed to clinical studies in humans., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as "cipó-uva" or "cipó-timbó". Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects., Material and Methods: We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia-reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE2, vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated., Results: The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro. In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro, the extract also displayed evident antimicrobial effects against Helicobacter pylori. However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine., Conclusions: Despite the anti-H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The leaves of Sedum dendroideum, commonly known as balsam, have long been employed for the treatment of gastric ulcers. The aim of study was to evaluate the antiulcer activity and toxicological properties of Sedum dendroideum using induced gastric ulcer models in Wistar rats., Materials and Methods: The hydroethanolic extract of Sedum dendroideum (ESD) was analyzed using an acute ulcer model using ethanol and indomethacin and a chronic ulcer model using acetic acid. The toxicity was evaluated with acute and subacute toxicity tests. The gastric secretion was assessed by the performance of pyloric ligation and the gastric volume, pH, and hydrogen ion concentration. The mechanism of the gastroprotective activity of ESD through the involvement of nitric oxide and sulfhydryl compounds was assessed. Moreover, a phytochemical screening and antioxidant assays were performed., Results: No signs of toxicity were observed. In the ethanol-induced ulceration model, ESD doses of 25, 50, and 100mg/kg significantly reduced the gastric lesions by 66.03%, 71.11%, and 70.82%, respectively. In the indomethacin-induced ulceration model, ESD doses of 25, 50, and 100mg/kg significantly reduced the gastric lesions by 89.88%, 94.36%, and 90.64%, respectively. Treatment with ESD at 50mg/kg and cimetidine at 200mg/kg significantly reduced acetic acid-induced ulcerations and resulted in 92.99% and 77.16% cure, respectively. ESD doses of 25, 50, and 100mg/kg inhibited oxidation by 79.7%, 82.4%, and 82.3%, respectively. The antiulcer activity of ESD may involve sulfhydryl compounds, considering that this activity was inhibited in the animals treated with sulfhydryl compound blockers. Furthermore, ESD increased mucus secretion and reduced gastric acidity and volume., Conclusions: The leaf extract of Sedum dendroideum exhibited gastroprotective activity, potentially due to sulfhydryl compounds and antioxidant activity. Therefore, other studies are warranted to elucidate the antiulcer properties of these compounds., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation., Aim of the Study: The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents., Material and Methods: The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP., Results: The oral administration of HEEP (125, 250 and 500mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l-arginine (500mg/kg, i.p.) but not by naloxone (1mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3-30mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500mg/kg, p.o.) protected the rats against ethanol (88.4-99.8%) and indomethacin (53-72.3%) and increased the mucus levels of the gastric mucosa without producing an antisecretory effect. The phytochemical profile of HEEP obtained using HPLC-PDA showed secondary metabolites already reported for the genus, mostly flavonoids, gallotannins and proanthocyanidins., Conclusions: These data show for the first time that HEEP has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system, the synthesis of nitric oxide and the inhibition of the phosphorylation of p38α MAPK. HEEP also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production. These results support the use of Eugenia punicifolia in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: An ethnopharmacological survey indicated that the bark from Qualea parviflora Mart. (Vochysiaceae) could be used to treat gastrointestinal disorders, such as diarrhea and intestinal inflammation. The objective of this study was to evaluate the effects of a methanolic extract from the bark of Qualea parviflora (QP) in an experimental model of diarrhea and intestinal inflammation induced in rodents., Material and Methods: The antidiarrheal and antispasmodic effects of QP were investigated by measuring intestinal motility, diarrhea, and intestinal fluid accumulation in rodents after challenging with a cathartic agent. In addition, the effects of QP on the contractility of the isolated mice-ileum preparation were determined. Acute intestinal inflammation was induced in male Wistar rats by the rectal administration of trinitrobenzenesulfonic acid (TNBS) in 50% ethanol (0.25 mL). QP was administered orally (for 5 days) prior to the induction of inflammation. The colonic injury and extent of inflammation were assessed by macroscopic damage scores and lesion length. The enhanced colonic mucosal injury, inflammatory response, and oxidative stress were evaluated by myeloperoxidase (MPO) activity; the tumor necrosis factor alpha (TNF-α), interleukin 1β (IL1-β), and malondialdehyde (MDA) levels; and the glutathione (GSH) content., Results: Oral treatment with QP (500 mg/kg) delayed the onset of diarrhea, reduced the amount of liquid stool, and decreased the severity of the diarrhea and the evacuation index in rodents challenged with castor oil (p<0.01). Additionally, QP (150-500 µg/mL) demonstrated effective antispasmodic activity against carbachol-induced contractions of mouse ileum in vitro. Oral treatment (25 and 50 mg/kg/day) with QP significantly reduced the intestinal inflammation induced by TNBS in rats (52% and 45%, respectively). Improvement of colonic mucosal injury by treatment with QP was demonstrated by a decrease in MDA levels and an increase in GSH content in colonic tissue. QP also prevented intestinal inflammation as evidenced by reduced cytokine levels (TNF-α and IL1-β) and low MPO activity., Conclusions: The ethnopharmacological usefulness of the bark from Qualea parviflora against diarrhea containing blood and mucus was supported by the observed antidiarrheal, antispasmodic, and intestinal antiinflammatory properties of this medicinal plant., (© 2013 Published by Elsevier Ireland Ltd.)

Ethnopharmacological Relevance: There is no evidence in the literature that substantiates the safety of Campomanesia xanthocarpa (Berg.) use during pregnancy., Materials and Methods: Thirty three female rats were randomly assigned to three groups. One group of animals received the Campomanesia xanthocarpa extract via gavage at a dose of 26.3mg/kg/day from 6 to 15 days of pregnancy (organogenic period, T1) and another group received the same extract throughout the gestational period (from the 1st to the 20th day of pregnancy, T2). Control groups received distilled water. Euthanasia was done on 20th day, when the liver, kidney, spleen ovaries, fetuses and their respective placentas were removed. Implantations, reabsorptions, live and dead fetuses were recorded., Results and Conclusions: Campomanesia xanthocarpa, in these experimental conditions, did not disturb the reproductive function of female rats and did not interrupt the progress of the embryofetal development. Moreover, our results provide further evidence that the Campomanesia xanthocarpa treatment reduces reabsorption sites, increases placenta weight and the number of live fetuses and may therefore have therapeutic applications., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Hyptis fruticosa is a plant native to Brazil with antinociceptive and antiinflamatory properties. This study evaluated the antinociceptive activity of the hydroethanol extract of the plant leaves (CHEE) against orofacial pain as well as its in vitro effect against lipid peroxidation., Materials and Methods: The antinociceptive activity was investigated in mice orally treated with different doses of the CHEE (50, 100, and 200 mg/kg) and morphine (5 mg/kg) using formalin, glutamate, and capsaicin orofacial pain models using. Lipoperoxidation was induced in egg yolk by AAPH and FeSO4 in the absence and presence of the CHEE (5, 50, 100, and 150 μg/mL)., Results: CHEE (200 mg/kg) significantly reduced (ρ<0.001) the pain response in the first (69.6%) and second (81.8%) phases of the formalin test, while the nociception caused by capsaicin was significantly (ρ<0.001) reduced by up to 62% at 200 mg/kg of extract. When glutamate was used as algogen, a significant (ρ<0.001) nociception reduction of up to 85% at 200 mg/kg extract was observed. CHEE showed a higher protection against lipoperoxidation caused by FeSO4 (82.3% TBARS inhibition) than AAPH (35.7% TBARS inhibition) at 150 μg/mL., Conclusion: Hyptis fruticosa leaf CHEE is of pharmacological interest because it was able to inhibit the peripheral and central transmission of orofacial pain, while reducing the spreading of the inflammatory processes by neutralizing reactive oxygen species, which are by-products in the biosynthesis of pain mediators., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Jacaranda decurrens subsp. symmetrifoliolata Farias and Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory diseases. However, until this moment, there is no scientific evidence of these effects., Aim of Study: To evaluate the anti-inflammatory effects of hydroethanolic root extract of Jacaranda decurrens in rats and to determine the safe of this plant after acute exposure., Materials and Methods: The acute toxicity of Jacaranda decurrens root extract (EJD) was evaluated by oral administration to male rats as single doses of 0; 500; 1000 or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in carrageenan-induced inflammatory paw edema and myeloperoxidase activity in male rats., Results: No signs of acute toxicity were observed, indicating that the LD(50) is greater than 2000 mg/kg. EJD (100 and 300 mg/kg) significantly reduced edema formation and at higher dose, the reduction was similar to dexamethasone. A significant decrease in myeloperoxidase activity was also observed., Conclusions: The present study shows that Jacaranda decurrens extract has anti-inflammatory properties in rats without causing acute toxicity. These properties observed may be due to the presence of bioactive constituents such as ursolic acid., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae) is a medicinal species commonly found in the Brazilian savannah. The stem bark of this medicinal plant, popularly known as "jatobá-do-cerrado", is widely used in tea form to treat gastric pain, ulcers, diarrhoea and inflammation, whereas its fruits pulp is edible., Aim of the Study: The aim of this study was to investigate the antidiarrheal and anti-ulcer effects of a methanolic extract derived from the stem bark (MHs) and diet with fruit pulp of H. stigonocarpa., Materials and Methods: The antidiarrheal action of MHs was measured against the intestinal motility and diarrhoea induced by castor oil in mice. The preventive action of MHs (50, 100, 150 and 200mg/Kg, by oral route (p.o.)) against peptic ulcers was evaluated in experimental rodent models challenged with absolute ethanol, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion (I/R) (200mg/Kg, p.o.) and cysteamine (200mg/Kg, p.o.). The main anti-ulcer mechanisms of action of MHs were analysed as follows: evaluation of the gastric juice parameters, assessment of mucus adherence to the gastric wall, determination of the role of nitric oxide (NO) and sulfhydryl compounds (SH), glutathione (GSH) levels and myeloperoxidase (MPO) activity. The healing effects from MHs (200mg/Kg) and diet with fruit pulp (10%) against gastric and duodenal ulcers induced by acetic acid were also evaluated by treating rats over 7 or 14 consecutive days of treatment., Results: The phytochemical profile of MHs and fruit pulp indicated the presence of phenolic compounds (mainly flavonoids and condensed tannins). MHs (200mg/Kg, p.o.) displayed an antidiarrheal effect and were able to protect gastric mucosa against absolute ethanol (68% protection) and also against the injurious effect of NSAIDs (86% protection) when compared to the group treated with vehicle. These results were accompanied by the prevention of GSH depletion and an inhibition of MPO activity when compared to animals treated with vehicle (P<0.05). MHs markedly protected duodenal mucosa against injuries caused by cysteamine (98%) and also against I/R induced gastric ulceration (80%) when compared to the group treated with vehicle. Furthermore, MHs also prevented the GSH depletion of gastric mucosa relative to the control group treated with vehicle. NO appeared to be involved in this gastroprotective effect. MHs and diet with fruit pulp clearly demonstrated gastric healing actions after treatment for 7 (MHs - 53% inhibition) or 14 days (MHs - 60% inhibition and fruit pulp - 61% inhibition). Treatment with diet with fruit pulp for 7 days demonstrates a significant duodenal healing effect (71% inhibition) without any signs of toxicity., Conclusions: MHs clearly demonstrate antidiarrheal, gastroprotective and cicatrising effects in experimental gastric and duodenal ulcers, and the diet with fruit pulp displays duodenal healing effects. The observed effects may be associated with the antioxidant effect, which may be due the presence of condensed tannins and flavonoids in the bark and fruit of H. stigonocarpa., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: An ethnopharmacological survey indicated that the leaves of Byrsonima intermedia A. Juss. (Malpighiaceae), a medicinal species commonly found in the Brazilian Cerrado, can be used against gastroduodenal disorders, such as gastric ulcers and diarrhea., Aim of the Study: The objective of this study was to evaluate the effects of a methanolic extract of Byrsonima intermedia (MBI) leaves on gastric and duodenal ulcers and to assess the antimicrobial and antidiarrheal effects of this extract., Material and Methods: The anti-ulcerogenic effect of MBI was investigated with different ulcerogenic agents in rodents (mice and rats), including non-steroidal anti-inflammatory drug (NSAID), HCl/ethanol, pyloric ligature, absolute ethanol, cysteamine and ischemia-reperfusion. The gastroprotective effect of MBI was assessed by analysing the volume of gastric juice, pH, total acidity, mucus, NO, sulfhydryl compound, vanilloid receptor, glutathione (GSH) levels, and myeloperoxidase (MPO) activity in the gastric and duodenal mucosa. The gastric and duodenal healing effects of MBI were also evaluated during 7 or 14 days of treatment. The antidiarrheal action (measured by intestinal motility and diarrhea induced by castor oil) and anti-bacterial action of MBI against Staphylococcus aureus, Escherichia coli and Helicobacter pylori were also evaluated by microdilution methods., Results: The phytochemical profile from MBI indicated the presence of phenolic acids, flavan-3-ols, oligomeric proanthocyanidins, and flavonoids. MBI (500mg/kg, p.o.) significantly inhibited totally gastric and duodenal lesions (69%) and healed gastric (49% on 14 days) and duodenal lesions (45% on 7 and 14 days). The MBI exert gastroprotective action by participation of endogenous sulfhydryl compounds, vanilloid receptors and increase in GSH level to effective gastric and duodenal protection. MBI also displayed curative (42%) and preventive (49%) antidiarrheal effects by involvement of opiate receptors and also antimicrobial effects in vitro., Conclusions: Byrsonima intermedia leaves present gastroprotective, healing and antidiarrheal activities, supporting previous claims that its traditional use can treat gastrointestinal disorders., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Strychnos pseudoquina St. Hil. (Loganiaceae) is one Brazilian native medicinal species described in the first edition of the Brazilian Official Pharmacopoeia in 1929. This medicinal plant, popularly known as "quina-quina", "quina-branca" or "casca aromatica was very commonly used in folk medicine in tea form obtained from the bark and/or leaves as tonic, antipyretic, antimalarial and mainly against diseases of the liver, spleen and stomach., Aim of the Study: Previous study already characterized the gastroprotective action of this species The aim of the present study is to elucidate the mechanism of the healing process mediated by the methanolic extract (ME) and their enriched alkaloid fraction (EAF) from Strychnos pseudoquina in chronic gastric ulceration induced by 5% acetic acid in rats, an experimental model that accurately reflects human gastrointestinal disease., Material and Methods: The ME and EAF was administered orally in a single dose (based on previously study of dose-response curve) for 14 days after chronic ulceration was induced in rats. The healing effect of ME and EAF was evaluated by macroscopic and morphometric analyses, immunohistochemical assay (PCNA and SOD) and anti-Helicobacter pylori effect was evaluated by in vitro assay., Results: Our results demonstrated that EAF significantly reduced border internal (42%) and external (38%) lesion area (mm(2)) by macroscopic analyses (P<0.05). Animals treated with EAF stimulated some proliferative factors by increasing the height of epithelial regenerative area and the expression of PCNA-positive nuclei. The number of vessels in gastric mucosa of rats treated with EAF reveals an expressive increase (4 times more than vehicle treatment) of vessels that stimulate cells proliferation in the healing region. These results suggest that the recovery of vascularization of the ulcerated area is involved in the healing action of alkaloid fraction of Strychnos pseudoquina. The MIC (minimum inhibitory concentration) of 75 μg/ml from EAF showed an effective in vitro anti-Helicobacter pylori action of this fraction. EAF also was quite effective in the process of SOD release that is an important protective factor against bacterial agents. The efficacy of EAF was accomplished safely without presenting any alteration of toxicological parameters during 14 day of treatment., Conclusions: The expressive gastric healing effect by increasing cellular proliferation together with expression of SOD activity and antibacterial action against Helicobacter pylori confirm the efficacy of this species in heal gastric mucosa and these results are a important contribution to the knowledge of a crude drug presents at the Brazilian Official Pharmacopoeia since 1929., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Indigofera suffruticosa is specie typical of the "Cerrado" or Brazilian savannah; it is a member of the Fabaceae family - in folkmedicine is used for gastric disorders, infection and inflammation., Aim of the Study: Ethyl acetate fraction (AcF) and aqueous fraction (AqF) of the methanolic extract of I. suffruticosa leaves were evaluated against acute gastric ulcer. The AcF fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion., Materials and Methods: The gastroprotective action of AcF and AqF fractions were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action, mucus and prostaglandin production, toxicological and healing activity of the AcF (100mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA and HSP-70) assays to evaluate the effects of I. suffruticosa., Results: AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant in 100mg/kg group compared vehicle. AcF did not interfered with gastric secretion, significantly increased the PGE(2) and mucus production (validated in PAS technique). The gastroprotection was attenuated by pretreatment with N-ethylmaleimide, but not L-NAME. In acid-acetic-induced ulcer model AcF accelerated ulcer healing. Immunohistochemistry analysis showed induction of proliferating cell (PCNA) and heat shock protein (HSP 70)., Conclusions: These results showed that AcF acted as gastroprotective agent stimulating prostaglandin, mucus and HSP70., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Hyptis Jacq. (Lamiaceae) is being used in traditional medicine to treat fever, inflammation and gastric disturbances. Hyptis spicigera Lam. is a native plant distributed across the central region of Brazil. The essential oil extracted from this plant is used in folk medicine as antipyretic., Aim of the Study: The effects of the essential oil obtained from the aerial parts of Hyptis spicigera (OEH) were evaluated for their gastroprotective and healing activities., Materials and Methods: OEH chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The gastroprotective action of the OEH was evaluated in rodent experimental models (ethanol and NSAID). To elucidate mechanisms of action, the antisecretory action and involvements of NO, SH, mucus and PGE2 were evaluated. The acetic acid-induced gastric ulcer model and Western Blot assay (COX-2 and EGF) were also used to evaluate the OEH healing capacity., Results: GC-MS analysis of OEH indicated three monoterpenes as major compounds: alpha-pinene (50.8%), cineole (20.3%) and beta-pinene (18.3%) and, at the dose of 100 mg/Kg, p.o., OEH provided effective gastroprotection against lesions induced by absolute ethanol (97%) and NSAID (84%) in rats. OEH do not interfere with H+ secretion in gastric mucosa and its gastric protection does not depend on nitric oxide (NO) and sulfhydryl compounds (SH). The gastroprotective action of OEH occurs due to an increase in the gastric mucus production (28%) induced by PGE2 levels. Furthermore, OEH demonstrated a great healing capacity with 87% of reduction in ulcerative lesion area. It accelerated the healing of acetic acid-induced gastric lesions due to an increase in COX-2 (75%) and EGF (115%) expression in gastric mucosa. No sign of toxicity was observed in this study, considering the analyzed parameters., Conclusions: All these results suggest the efficacy and safety of Hyptis spicigera in combating and healing gastric ulcer. Considering the results, it is suggested that the OEH could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: Mouriri pusa, popularly known as "manapuçá" or "jaboticaba do mato", is a plant from Brazilian cerrado that has been found to be commonly used in the treatment of gastrointestinal disturbs in its native region. The present work was carried out to investigate the effect of tannins (TF) and flavonoids (FF) fractions from Mouriri pusa leaves methanolic extract on the prevention and cicatrisation process of gastric ulcers, and also evaluate possible toxic effects., Materials and Methods: The following protocols were taken in rats: acute assay, in which ulcers were induced by oral ethanol after pre-treatment with the fractions; and 14 days treatment assay, in which ulcers were treated for 14 days after induction by local injection of acetic acid., Results: In the acute model, treatment with either, TF (25mg/kg) or FF (50mg/kg), was able to reduce lesion area, showing gastroprotective effect. In addition, FF proved itself anti-inflammatory by reducing COX-2 levels. In acetic acid model, both fractions exhibited larger ulcers' regenerative mucosa, indicating cicatrisation enhancement. FF group also showed augmented cell proliferation, anti-inflammatory action and enhanced angiogenesis as well as increased mucus secretion. Moreover, concerning the toxicity parameters analyzed, no alteration in the fractions groups was observed., Conclusions: Tannins and flavonoids from Mouriri pusa provide beneficial effects against gastric ulcers with relative safety., ((c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Davilla elliptica and Davilla nitida are species commonly found in the Brazilian Cerrado biome., Aim of the Study: Based on ethnopharmacological and phytochemical analyses, methanolic extracts from leaves of Davilla elliptica (EDE) and Davilla nitida (EDN) were evaluated for their anti-ulcer, anti-inflammatory, immunological and anti-Helicobacter pylori activities., Materials and Methods: The gastroprotective action of both extracts was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated anti-inflammatory (carrageenin-induced rat hind paw edema), immunomodulatory (murine peritoneal macrophages) and antibacterial action of both extracts against a standard strain of Helicobacter pylori., Results: EDE and EDN (500 mg/kg) were able to protect gastric mucosa against HCl/ethanol solution (EDE 63%; EDN 59%), absolute ethanol (EDE 95%; EDN 88%), and also against injurious effect of NSAID (EDE 77%; EDN 67%). When EDE and EDN were challenged with sulfhydryl depleter compound, the gastroprotective action of both extracts was completely abolished. EDE had gastroprotective effect related to increase of glutathione bioavailability and stimulated higher levels of NO, H2O2 and TNF-alpha production. Otherwise EDN showed better anti-Helicobacter pylori action than EDE. Neither extracts presented anti-inflammatory activity by oral route., Conclusion: The phytochemical investigation showed that both extracts possess phenolic acid derivatives, acylglycoflavonoids and condensed tannins with evident quantitative variations that probably influenced the pharmacological differences between extracts.

Ethnopharmacological Relevance: Mouriri elliptica Martius (Melastomataceae) is species reputed in folk medicine to heal gastric ulcer and gastritis., Aim of the Study: Methanolic extract (ME) and ethyl acetate fraction (EAF) from leaves of Mouriri elliptica were evaluated for their gastroprotective, healing, immunological, toxicological and anti-Helicobacter pylori activities., Material and Methods: The gastroprotective action of ME and EAF was evaluated in rodent experimental models and to elucidate mechanisms of action, the antisecretory action, involvements of NO, SH, PGE(2), anti-Helicobacter pylori action of ME was evaluated. We also used immunohistochemical (PCNA and COX-2) and immunomodulatory (murine peritoneal macrophages) assays to evaluate Mouriri elliptica effects., Results: ME present gastroprotective action without antisecretory effect. Otherwise, ME showed anti-Helicobacter pylori action (MIC=0.025mug/mL) and was able to inhibit NO production by macrophages. This species also accelerate the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA), COX-2 and maintained basal PGE(2) level independent action of NSAID in gastric mucosa. The phytochemical investigation showed that this species possesses phenolic acid derivatives, acylglycoflavonoids and condensed tannins which probably influenced their pharmacological action., Conclusion: All these results suggest the efficacy and safety of Mouriri elliptica in combating and healing gastric ulcer.

Ethnopharmacological Relevance: Virola surinamensis (Myristicaceae), popularly known as "mucuíba", "ucuuba" or "ucuúba do igapó" is a large tree that grows abundantly in "Várzea" forest and on river banks in the Brazilian states of Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed folk remedy in its natural form for the treatment of ulcer, gastritis, inflammation and cancer., Aim of the Study: The present work evaluated the pharmacological activity of the resin obtained from bark of V. surinamensis as antiulcerogenic in experimental in vivo model in order to observe whether its traditional use is justified., Materials and Methods: The preventive action of ethanolic extract of V. surinamensis was evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa., Results: Oral administration of acidified ethanol solution produced severe hemorrhagic lesions in glandular mucosa with ulcerative lesion of 50+/-11.5mm. In animals pretreated with V. surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury of 2.40+/-0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same dose, also reduced significantly (p<0.05) the formation of gastric lesions induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%) when compared to animals treated with vehicle. The extract from V. surinamensis exerts gastroprotective action only when this extract contacts gastric mucosa (oral route) with increased pH values and reduced H+ concentration of gastric contents. The ethanolic extract of V. surinamensis resin was analyzed by TLC and spectrometric methods (NMR and ES-MS) and the main constituent of this extract was epicatechin., Conclusions: We suggest that the epicatechin present in V. surinamensis resin may be among active principles responsible for the antiulcer activity shown by the tested resin but their used suggest carefulness because toxicological symptoms mentioned by population.

Ethnopharmacological Relevance: Curatella americana L. (Dilleneaceae) is a medicinal plant very frequently cited as acting against gastrointestinal disorders in ethnopharmacological inventories of the Cerrado region of Brazil., Aim of the Study: The ethanolic extract (CEB) and infusion (BI) of Curatella americana bark were investigated for their ability to prevent and heal ulceration of the gastric mucosa., Materials and Methods: The preventive and healing actions of Curatella americana were evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa., Results: CEB significantly decreased the severity of gastric damage formation induced by the combination of several gastroprotective models (HCl/ethanol, indomethacin/bethanecol, absolute ethanol, stress and pylorus ligature). But, unlike CEB, the BI did not exert gastroprotective effect. The gastroprotective action of CEB involved antisecretory action, augmentation of gastric mucus (48%) and participation of endogenous sulfhydryl compounds that increase efficacy of barrier mucosa against injurious agents. CEB also presents effective healing action in chronic gastric disease (1.90+/-0.55 vs. 6.86+/-0.46 mm2)in the control) and its action mechanisms consisted of increasing the PGE2 (40%) and somatostatin levels (269%) while decreasing the gastrin level in rat plasma (79%)., Conclusions: The gastroprotective effect and healing action of Curatella americana involved modulation of PGE2, somatostatin and gastrin levels, probably due to the presence of oligomeric and polymeric proanthocyanidins in the bark.

Aim of the Study: Vochysia tucanorum is an important medicinal plant used in the Cerrado of Brazil against gastric disorders and this study reveals the pharmacological action of this traditional medicine use., Materials and Methods: The methanolic extract (E-MeOH) and buthanolic fraction (Fr-Bu) obtained from V. tucanorum were challenged by different necrotizing agents in rodents. NO-synthase inhibitor (L-NAME) and SH blocker (NEM) were used to evaluate the participation of cytoprotective factors in E-MeOH and Fr-Bu gastroprotection. Antiulcerogenic action of V. tucanorum was evaluated in rats and mice at doses 250, 500 or 1000 mg/kg (E-MeOH) and 37.5, 75 or 150 mg/kg (Fr-Bu)., Results: Both E-MeOH and Fr-Bu present elevated gastroprotective action in all in vivo experimental models, without signs of acute toxicity. The mechanisms involved in the gastroprotective action of E-MeOH and Fr-Bu are related to the antioxidant activity and protection to gastric mucosa NO levels. Phytochemical investigations of Fr-Bu identified different pentacyclic triterpenoids such as betulinic acid, erythrodiol, epi-betulinic acid and mixtures of ursolic acid and oleanolic acid derivatives as the major constituents. The presence of such triterpenoids in Fr-Bu is probably related to the potent gastroprotective action of this medicinal plant species., Conclusion: Effectiveness in gastroprotection and the absence of acute toxicity indicate this species as a promising herbal drug that is in accordance with ethnopharmacological use against gastric disorders.

Ethnopharmacological Relevance: Mangaba (Hancornia speciosa Gomez) is a medicinal plant frequently cited in ethnopharmacological inventories of the central region of Brazil against gastrointestinal disorders such as diarrhoea, ulcer, gastritis and stomach ache., Aim of the Study: The hydroalcoholic extract (HE) and infusion (BI) of Hancornia speciosa bark were investigated for their ability to prevent and heal rodent gastric ulcer., Materials and Methods: The preventive and healing action of both preparations of Hancornia speciosa were evaluated in experimental models in rodents that simulated this disease in human gastric mucosa., Results: BI did not exert gastroprotective effect, in contrast to HE (500mg/kg, p.o.) that decreased (p<0.05) the severity of gastric damage induced by HCl/ethanol (52%), indomethacin/bethanechol (51%), stress (52%) or pylorus ligature experiments (54%). HE increased (p<0.05) the pH and decreased acid output of gastric juice. This extract promoted increase of mucus amount (3.62mg/wt. tissue vs. 5.81mg/wt. tissue), healing action (67%) and displayed anti-Helicobacter pylori effect., Conclusions: The antiulcer action of Hancornia speciosa resulted in increase of gastric mucus formation and antioxidant properties of polymeric proanthocyanidins present in the bark composition of this medicinal plant.

Ethnopharmacological Relevance: Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders., Aim of the Study: The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF) was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities., Materials and Methods: The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters., Results: Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. BF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro., Conclusions: Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments.

Aim of the Study: Cissus sicyoides L. is a medicinal plant popularly known in Brazil against various diseases and the research interest in this plant is justifiable because of its potential medicinal value in stomachache and gastric ulcer., Materials and Methods: The methanolic extract obtained from the leaves of Cissus sicyoides (Cc) was evaluated for the ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, piroxicam and pylorus ligature) in rodents. We also evaluated microcirculation, antioxidant action and participation of NO (nitric oxide) and sulfhydryls (SH) groups in the Cc gastroprotective action., Results: Administration of Cc significantly reduced gastric lesions induced by different ulcerogenic agents in rodents. This extract administered by oral route significantly increased gastric volume without exerting antisecretory effect. The Cc effect involved an increase of the defense mechanism of the gastrointestinal mucosa such as NO and SH groups that prevent and attenuate the ulcer process. The Cc also has antioxidant property against oxidative stress but does not modify microcirculation response in gastric mucosa., Conclusions: These results confirmed the traditional use of Cissus sicyoides for the treatment of gastric ulcer.

Ethnopharmacological Relevance: Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used by people living in the Cerrado to treat gastrointestinal disturbances. This medicinal plant has shown intense gastroprotective action in rodent gastric lesion, but still there are no data about its healing effect on gastric mucosa., Aim of the Study: To evaluate the methanolic extract (MeOH) obtained from Mouriri pusa leaves for its effect on the cicatrisation process of gastric ulcer., Materials and Methods: The healing effects on gastric ulcers inducted by subserosal injection of acetic acid were evaluated by macroscopic and microscopic measures, immunohistochemistry and cell counting in rats treated with MeOH extract of Mouriri pusa (250 mg/kg, p.o./daily) for 14 or 30 days. The toxicity of Mouriri pusa was also evaluated by body and organ weight measure and clinical biochemical parameters., Results: Mouriri pusa treatments lasting 14 and 30 days showed elevated mucus secretion (PAS) and thicker regenerative gastric mucosa, denoting increased cell proliferation, which was confirmed by PCNA immunohistochemical analysis. Moreover, there was important cell recruitment (neutrophils and mast cells) to the site of the ulcer, which is an important factor in ulcer healing. No toxic effect was observed in all parameters evaluated. Phenolic compounds present in the MeOH extract like tannins, flavonoids and epicatechin are the probable agents involved in the healing effects of this medicinal plant., Conclusions: These findings showed a potential effect of Mouriri pusa in increasing regeneration of damaged gastric mucosa with safety for human use.

Several plants are used in folk medicine to treat gastrointestinal disorders. Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used in the central region of Brazil against gastric ulcer. Two organic extracts methanolic (MeOH) and dichloromethane (DCM) obtained by sequential extraction from the leaves of Mouriri pusa were evaluated for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3M HCl/60% EtOH, absolute ethanol, non-steroidal anti-inflammatory drug, stress and pylorus ligature) in mice and rats. The best results were obtained after pretreatment with MeOH extract whereas the DCM extract did not show the same significant antiulcerogenic activity. No acute toxicity was observed in animals treated with 5 g/kg, p.o. of MeOH extract. The mechanism involving the antiulcerogenic action of MeOH extract seemed to be related to NO generation and also suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. Phytochemical investigation of the MeOH extract of Mouriri pusa yielded tannins, flavonoids and (-)-epicatechin. The presence of these phenolic compounds probably would explain the antiulcerogenic effect of the polar extract of Mouriri pusa leaves.

This study was designed to determine the effect of Mangifera indica flowers decoction, on the acute and subacute models of induced ulcer in mice and rats. A single oral administration of the aqueous decoction (AD) from M. indica up to a dose of 5 g/kg, p.o. did not produce any signs or symptom of toxicity in the treated animals. The oral pre-treatment with AD (250, 500 and 1000 mg/kg) in rats with gastric lesions induced by ethanol, decreased the gastric lesions from 89.0+/-6.71 (control group) to 9.25+/-2.75, 4.50+/-3.30 and 0, respectively. Pretreatment with AD (250, 500 and 1000 mg/kg) to mice with HCl/ethanol- or stress-induced gastric lesions resulted in a dose-dependent significant decrease of lesion index. In the piroxicam-induced gastric lesions, the gastroprotective effect of AD was reducing with the increase of the AD dose. In the pylorus-ligature, AD (p.o.) significantly decreased the acid output indicating the antisecretory property involved in the gastroprotective effect of M. indica. Treatment with AD during 14 consecutive days significantly accelerated the healing process in subacute gastric ulcer induced by acetic acid in rats. Pretreatment with N-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO-synthase, did not abolish the gastroprotective effects (99% with saline versus 80% with l-NAME) of AD against ethanol-induced gastric lesions. Pretreatment with N-ethylmaleimide (NEM), a blocker of endogenous sulphydryl group, significantly abolished the protective effects of AD against ethanol-induced gastric ulcers (95% with saline versus 47% with NEM). Phytochemical screening showed the presence of steroids, triterpenes, phenolic compounds and flavonoids. Estimation of the global polyphenol content in the AD was performed by Folin-Ciocalteu method and showed approximately 53% of total phenolic on this extract. These findings indicate the potential gastroprotective and ulcer-healing properties of aqueous decoction of M. indica flowers and further support its popular use in gastrointestinal disorders in Caribbean.

The hydroethanolic extract of the leaves (HEL) and bark (HEB) obtained from Alchornea castaneaefolia (Euphorbiaceae) were investigated for their ability to prevent ulceration of the gastric mucosa in animal models. HEL (500 and 1000 mg/kg) and HEB (1000 mg/kg) significantly reduced the gastric injuries induced by the combination of HCl/ethanol and lowered the severity of gastric damage formation induced by indomethacin/bethanechol in mice. Further investigation showed that HEL also inhibited formation of ulcers in mice submitted to stress and pylorus ligature, but HEL did not modify gastric juice parameters in Shay mice. HEL was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats. An enriched flavonoidic fraction (EFF at dose of 100mg/kg) obtained from HEL reduced gastric lesions induced by HCl/ethanol and indomethacin/bethanechol in mice. Although EFF did not modify the amount of free mucus production by gastric mucosa, it was able to increase prostaglandin production. When administered to rats submitted to ethanol-induced gastric lesions, EFF increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. Phytochemical investigation on HEL and EFF led to the isolation of flavonoids glycosides as the main compounds, thus suggesting that these substances may be involved in the observed antiulcer activity.

Pradosia huberi is a medicinal plant very common in the Amazonian forest population. The research interest in this plant is justifiable because of its potential medicinal value in gastritis and gastric ulcer mentioned in local folk medicine. In this paper, we evaluated the acute toxicity and antiulcerogenic effect of a hydroalcoholic extract (HAE) obtained from Pradosia huberi barks in rodents. No acute toxicological sign or symptom was observed in animals treated with the highest dose (5000 mg/kg, p.o.) of Pradosia huberi. In the HCl/EtOH-induced gastric ulcer model, HAE demonstrated significant inhibition of the ulcerative lesion index by 73% (500 mg/kg) and 88% (1000 mg/kg), respectively, in relation to the control value (p<0.05). The gastric damage induced by absolute ethanol in rats was effectively reduced by 84, 88 and 81% (250, 500 and 1000 mg/kg) when compared with the control group (p<0.01). In the NSAID-induced lesion model, HAE also showed antiulcerogenic effect with decrease in gastric lesions of 56% (250 mg/kg), 57% (500 mg/kg) and 67 % (1000 mg/kg) when compared with animals treated with vehicle (p<0.05). In the gastric ulcer induced by pylorus ligature model, the administration of HAE by oral and intraduodenal routes inhibited the gastric lesion index by 79 and 52% (500 mg/kg), respectively. HAE administered orally or intraduodenally was able to change gastric juice parameters (pH, volume and acid output) as well as those treated with cimetidine. The treatment with HAE (p.o.) significantly increased gastric volume, the pH values and promoted reduced acid output (p<0.01). By comparative effect (intraduodenal and oral route), we observed that HAE was better for local activity in gastric mucosa than in systemic action. HAE also has a non-specific activity when found to be the inhibitor of intestinal motility (p>0.01). The mechanism of action of HAE did not seem to be related to the NO-inhibitor but showed the participation of endogenous sulphydryl group in the gastroprotective action.

Byrsonima crassa Niedenzu (IK) (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In this study, we evaluated the potential antiulcerogenic effect of three different extracts obtained from the leaves of Byrsonima crassa namely hydromethanolic (80% MeOH), methanolic (MeOH) and chloroformic extracts (CHCl(3)). The oral administration (250, 500 and 1000 mg/kg) of all the extracts reduced the formation of lesions associated with HCl/ethanol administration in mice. The 80% MeOH extract significantly reduced the incidence of gastric lesions by 74, 78 and 92% at doses of 250, 500 and 1000 mg/kg, respectively (P<0.01). The MeOH extract reduced the ulceration by 93 and 99% only at the doses of 500 and 1000 mg/kg (P<0.01). The lower gastroprotective action (69%) was observed when animals were treated with CHCl(3) extract at the dose of 1000 mg/kg (P<0.01). Phytochemical investigation of Byrsonima crassa afforded five known substances: quercetin-3-O-beta-d-galactopyranoside, quercetin-3-O-alpha-l-arabinopyranoside, the biflavonoid amentoflavone, (+)-catechin and (-)-epicatechin. The presence of these phenolic compounds may probably explain the antiulcerogenic effect of the extracts of Byrsonima crassa leaves.

The effect of three new derivatives from dehydrocrotonin (DHC-compound I) on gastric damage in different animal models including gastric ulceration induced by a necrotic agent and hypothermic restrained-stress was studied: compound II (produced by reducing the cyclohexenone moiety of DHC with NaBH(4)); compound III (produced by reducing the carbonyls with LiAlH(4)); and compound IV (produced by transforming the lactone moiety into an amide). Their structures were confirmed on the basis of chemical and physicochemical evidence. When previously administered (p.o.) at a dose of 100mg/kg, compound II significantly (P<0.01) reduced gastric injury induced by HCl/ethanol (78%) and indomethacin (88%) better than did reference compound I (48 and 43%, respectively). But the anti-ulcerogenic activity of compound II was completely abolished by the stress-induced ulcer. Reduction of carbonyls with LiAlH(4) (compound III) caused decreased activity, markedly when no protective effect in any of the models was applied (P>0.05). However, compound IV, in which the lactone moiety was changed into an amide, when administered at the same dose (100mg/kg, p.o.), was more effective. The presence of a lactone moiety or Michael acceptor is probably essential for the anti-ulcerogenic effect of these compounds.

We evaluated the possible antiedematogenic, antinociceptive and/or sedative effects of four different extracts obtained from the bark of Quassia amara namely, 70% ethanol (70EtOH), 100% ethanol (100EtOH), dichloromethane (DCM) and hexane extracts (HEX). The oral administration (100, 250 and 500 mg/kg) of these extracts did not show significant effects in any experiment. However, when administered intraperitoneally, the HEX extract decreased the paw edema induced by carrageenan, showed antinociceptive effects on the hot-plate test and on acetic acid-induced writhing, and showed sedative effects on pentobarbital-induced sleep. Naloxone did not reverse the antinociceptive effect of this extract. In conclusion, although the mechanisms are uncertain, the results demonstrated that these effects are apparently related to sedative and muscle relaxant or psychomimetic activities of the HEX extract of the plant.

The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used in Martinican folk medicine for its analgesic and anti-inflammatory properties. In the present investigation we studied the acute oral (p.o.) toxicity of a crude extract obtained from a lyophilized decoction (DE) and from the juice (JE) of fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B. diffusa were assessed in standard rodent models of algesia and inflammation. We investigated the antinociceptive effect of DE and JE in chemical (acetic acid) and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200 mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47% inhibition, respectively) when compared with the negative control (P<0.001). In the hot-plate test in mice, morphine and JE produced a significant increase in latency during the observation time. The DE, however, only raised the pain thresholds during the first period (30 min) of observation (P<0.05). The extracts of B. diffusa were also investigated for their anti-edematogenic effect on carrageenan-induced edema in mice. However, neither extract inhibited the paw edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly reversed the analgesic effect of morphine and JE but not that of DE. These data show that the active antinociceptive principle of B. diffusa is present mainly in the juice of fresh leaves and has a significant antinociceptive effect when assessed in these pain models. The mechanism underlying this analgesic effect of fresh leaves of B. diffusa remains unknown, but seems to be related to interaction with the opioid system.

The gastroprotective activity of the essential oil from the bark of Croton cajucara Benth (Euphorbiaceae) was assessed in three different models of experimentally induced gastric ulcer in mice. At oral dose of 100 mg/kg the essential oil reduced gastric lesions induced by hypothermic restraint stress and HCl/ethanol significantly. In the HCl/ethanol model a dose-dependent gastroprotective effect was found. Moreover, significant changes in gastric parameters such as pH, secretion rate and total gastric acid were found after intraduodenal administration of essential oil under ligated pylorus (Shay) conditions. The acute toxicity of essential oil was assessed in mice. The LD50 values were 9.3 and 680 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of essential oil was studied also. A dose-dependent cell viability inhibition was found in V79 fibroblast cell cultures with an IC50 of 22.9 microg/ml. Our results support the pharmacological study of this essential oil.