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

Abstract: Ethnopharmacological relevance: Garcinia achachairu Rusby (Clusiaceae) is popularly known as “achachairu”, and is used in Bolivian folk medicine for its healing, digestive, and laxative properties, and in the treatment of gastritis, rheumatism and inflammation. Despite its widespread therapeutic use, there is a lack of data regarding its in vivo genotoxic effects. Therefore, in this study, we used the comet assay and the micronucleus test, respectively, to evaluate the possible genotoxic and clastogenic effects of Garcinia achachairu seed extract (GAE) on different cells of mice. Material and methods: The GAE was administered by oral gavage at doses of 500, 1000 and 2000mg/kg. For the analysis, the comet assay was performed on the leukocytes (collected 4 and 24h after treatment), liver, bone marrow and testicular 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 results showed that GAE did not induce significant DNA damage in leukocytes (4h and 24h samples), liver, bone marrow and testicular cells (24h samples). GAE also did not show any significant increase in micronucleated polychromatic erythrocytes (MNPCEs) at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Under our experimental conditions, the data obtained suggest that a single oral administration of G. achachairu extract does not cause genotoxicity and clastogenicity in different cells of mice. [Copyright &y& Elsevier]

Abstract: Relevance: Simaba ferruginea A. St-Hil. (Simaroubaceae) is a subshrub typical of the Brazilian Cerrado, whose rhizomes are popularly used as infusion or decoction for the treatment of gastric ulcers, diarrhea and fever. Aim of the study: To evaluate the pharmacological mechanism(s) of action of the antiulcer effects of the methanol extract of Simaba ferruginea and its alkaloid canthin-6-one. Materials and methods: Rhizome of Simaba ferruginea was macerated with methanol to obtain the methanol extract (MESf) from which was obtained, the chloroform fraction. Canthin-6-one alkaloid (Cant) was purified and then isolated from the chloroform fraction (CFSf). The isolated Cant was identified by HPLC. Anti-ulcer assays were determined using ethanol and indomethacin-induced ulcer models in mice and rats respectively. In order to determine the probable mechanisms of actions of MESf and Cant animals were pretreated with l-NAME prior to anti-ulcer agent treatments and ulcer induction and nitric oxide (NO) level determined in order to assess NO involvement in the gastroprotective effects. Assays of malondialdehyde (MDA), myeloperoxidase (MPO), pro-inflammatory cytokines: interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2) were also carried out according to previously described methods. Results: The results indicate that the antiulcerogenic effects of MESf and Cant in ethanol-induced ulcer is mediated in part through increase in the production of protective endogenous NO as the antiulcerogenic activity of MESf and Cant was reduced in animals pre-treated with l-NAME. In indomethacin-induced ulcer pre-treatment with MESf and Cant showed reduction in the levels of MPO and MDA in the gastric tissue, thus indicating the participation of the antioxidant mechanisms on the gastroprotective effects. The plasma levels of IL-8 in ulcerated rats with indomethacin were also reduced by Cant, but not by MESf, indicating that inhibition of this cytokine contributes to the gastroprotective effect of Cant. However MESf and Cant had no effect on the mucosal membrane levels of PGE2, indicating that the gastroprotective effects of these agents is independent of PGE2 modulation. Conclusion: The results obtained in this study with MESf and Cant added insights into the pharmacological mechanisms involved in their mode of antiulcer action. The results indicate that Cant is one of the compounds responsible for these effects. Such findings are of extreme importance in the strive for future development of potent, safer and effective antiulcer agent. The efficacy of MESf and Cant in gastroprotection shows that Simaba ferruginea might be a promising antiulcer herbal medicine, in addition to confirming the popular use of this plant against gastric ulcer models utilised in this study. [Copyright &y& Elsevier]

Abstract Ethnopharmacological relevance Popular medicine use stems of Philodendron bipinnatifidum (Araceae) in inflammation cases, such as in erysipelas, as well as orchitis and rheumatism treatment. The present study, conducted for the first time in literature, investigate the antinociceptive and anti-inflammatory activities of P. bipinnatifidum stems ethyl acetate extract (EPB). Materials and methods GC/MS and HPLC analysis were performed for EPB extract. We used EPB at 250, 375 and 500 mg/kg (oral route, p.o.) in male Swiss mice. The antinociceptive activity of the plant extract assessed by acetic acid induced writhing and formalin tests. To investigate the possible participation of opioid system in EPB-mediated effects, we previously administered naloxone to the mice. Anti-inflammatory activity was evaluated using carrageenan-induced paw oedema. The open-field test aimed to investigate the possible EPB effects on the locomotor and exploratory activities. To assess the protective role of EPB on carrageenan-induced oxidative stress, the levels of NPSH, TBARS, as well as SOD and CAT activities were evaluated in blood and paw tissue. The acute toxicity of the EPB was investigated using OECD 423 guideline. Results The EPB chemical analysis by GC/MS and HPLC revealed the presence of flavonoids (luteolin and quercetin) and phytosterols (β-sitosterol and stigmasterol). The oral treatment with the EPB inhibited mice abdominal writhings (P < 0.01) at 375 and 500 mg/kg, and reduced the formalin effect at the first-phase (500 mg/kg, P < 0.05) and also at the second-phase (500 mg/kg, P < 0.001) of the test. E P B (375 and 500 mg/kg) did not alter spontaneous locomotion in open field test, however the number of fecal bolus was significantly lower for the EPB group at 500 mg/kg when compared to the vehicle group (P < 0.05). The pretreatment with naloxone caused significant inhibition of antinociceptive activity induced by EPB in the formalin test, revealing the possible involvement of opioid receptors. EPB extract administered at 500 mg/kg (p.o.) prevented carrageenan-induced paw oedema (P < 0.05 and 0.01) until 6 h after carragenan injection. Evaluation of TBARS and NPSH levels, SOD and CAT activities in the blood and paw tissue of animals submitted to the carrageenan assay suggested that the anti-inflammatory effect of EPB may be linked to oxidative stress inhibition. The acute administration of the EPB (2000 mg/kg, p.o.) caused no mortality, demonstrating low toxicity. Conclusions The extract of P. bipinnatifidum displays antinociceptive and anti-inflammatory activities, causing no toxicological effects. The pharmacological activity of this vegetal species may be related to the presence of flavonoids and phytosterols. Our results support the ethnomedical use of this vegetal species as analgesic and anti-inflammatory agent. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The leaves from Vernonia condensata Baker are broadly used in folk medicine for the treatment of gastric ulcers and dyspepsia. The Brazilian Public Health System (SUS) describes this species as having the potential to serve as a new herbal product with therapeutic benefits. Aim of the study The purpose of the study was to evaluate the gastroprotective activity and gastric healing properties of a crude ethanolic extract from leaves of V. condensata (CEEV) in different animal models. Materials and methods In order to assess the gastroprotective potential of CEEV, ulcer models were established using ethanol and indomethacin. The gastric healing effect was then evaluated in the acetic acid-induced ulcer model, where the tissue was used to assess oxidative levels (reduced glutathione and lipid hydroperoxide levels, as well as superoxide dismutase and catalase activity), inflammatory [myeloperoxidase (MPO)] parameters, and mucin content. Furthermore, the ligature pylorus model, with and without secretagogue stimuli, was employed to investigate the mechanism of action of CEEV. In addition, H + K + -ATPase activity, MPO activity, and antioxidant activity through the DPPH assay were examined through in vitro trials. Phytochemical analyses were also performed. The ethanol/HCl-induced gastric ulcer method was employed to verify the gastroprotective effect of the main compound in CEEV. Results CEEV (30 and 300 mg/kg, p.o) exhibited gastroprotective activity and prevented both gastric lesions induced by ethanol or indomethacin in rats. The gastric healing effect of CEEV (300 mg/kg, p.o. taken twice a day for a duration of seven days) was confirmed by examining the macroscopic and microscopic appearance of chronic gastric ulcers induced by acetic acid in rats. The restorative effect of CEEV was accompanied by a significant increase in mucin content (PAS staining) and by a reduction in oxidative stress and inflammatory parameters at the site of the ulcer. Moreover, CEEV (300 mg/kg), administered via an intraduodenal route, significantly reduced the volume, pH, total acidity and pepsin activity of gastric content in the pylorus ligature model in rats. The gastric acid antisecretory effect of CEEV was maintained even in the presence of cholinergic and gastrinergic, but not histaminergic, stimuli. In vitro , CEEV (1–10 µg/ml) was able to scavenge free radical DPPH, but did not promote inhibitory effects on MPO or H + ,K + -ATPAse activity. Phytochemical analysis of CEEV indicated that luteolin is the main compound present in the extract. However, luteolin (1, 3 and 10 mg/kg, p.o or 1 mg/kg, i.p.) did not promote gastroprotection against ethanol/HCl in mice. It is also important to mention that oral administration of CEEV did not produce any sign of acute toxicity in animals. Conclusions V. condensata extract demonstrates gastroprotective effects through the inhibition of gastric secretion via cholinergic and gastrinergic pathways. Furthermore, it exhibits cytoprotective effects, involving antioxidant activity, an increase in mucin content and inhibition of neutrophil migration. Thus, this medicinal plant may be a suitable natural source for the prevention and treatment of gastric lesions. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance In Brazil, a phytotherapeutic preparation produced from a standardized tincture of Cinchona calisaya Weddel such that each mL of product contains 400 µg of quinine, known in Portuguese as Água Inglesa ® (English water), is indicated by the manufacturer as a tonic, appetite stimulant, and digestive. However, this preparation has long been used in folk medicine as a female fertility stimulant. Despite its widespread use in folk medicine to stimulate female fertility, no study has been undertaken to assess the potential teratogenic and genotoxic effects of this phytotherapeutic preparation. The aim of the present study was to investigate possible toxic reproductive effects in mice caused by exposure to Água Inglesa ® , either before mating or during the pre- and post-embryo implantation periods. The genotoxic potential was evaluated using the micronucleus assay. Material, Methods, and Results Virgin female mice, with at least one estrous cycle evidenced by vaginal cytology, were divided into five groups of 15 individuals each (Group I – control, Group II – treated with ethanol solution at 16%, Groups III, IV and V treated with phytotherapeutic preparation at 1.5 mL/kg/day, 3.0 mL/kg/day and 4.5 mL/kg/day, respectively). After the first 28 days of treatment, females were caged individually with adult fertile males. Pregnant females continued to receive treatment for seven days (preimplantation period). Body weight was recorded weekly during treatment. Signs of toxicity (weight loss, food intake, piloerection, apathy, prostration, diarrhea, seizures, behavioral changes, and locomotion) were also observed. The females were sacrificed on the 15th day of pregnancy, uterine horns were evaluated for implantation, and the placental index was recorded. In the micronucleus test, 2000 polychromatic erythrocytes (PCE) per animal, obtained from bone marrow, were scored. Results The results showed that exposure of the females during the pre- and post-implantation periods did not significantly alter the reproductive capacity ( p <0.05); however, in higher dose (three times human dose)reduction of fetal weight was observed . There was no difference between the control and phytotherapeutic preparation ( p >0.05) in terms of the average number of micronucleated polychromatic erythrocytes. Conclusions Although folk medicine suggests that the Água Inglesa ® preparation is useful as a female fertility stimulant, no such effect was confirmed in mice. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Rubus imperialis Cham. Schl. (Rosaceae) is frequently used in traditional medicine as hypoglycemic, antinociceptive and antiviral remedy. Materials and methods: Swiss albino mice were distributed in eight groups for acute treatment with Rubus imperialis extract (24h). The extract doses selected were 50, 250 and 500mg/kg b.w. administered by gavage alone or plus to CPA (50mg/kg b.w.) administered by intraperitoneal injection. Control groups were treated in a similar way. Analyses were performed using the comet assay, on leukocytes (collected 4 and 24h after treatment) and liver (collected 24h after treatment), and using the micronucleus test (MN) in bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). Results and conclusion: The main compounds identified in the Rubus imperialis extract were saponins and steroidal compounds, with niga-ichigoside and tormentic acid being the major compounds. Tested doses of Rubus imperialis extract showed no genotoxic effects on leukocytes from peripheral blood or liver cells by the comet assay. However, the MN test showed an increase in the frequency of micronucleated cells at the two higher doses tested, indicating that this extract has clastogenic/aneugenic effects on bone marrow cells at higher doses. On the other hand, for all cells evaluated, the three tested doses of the Rubus imperialis extract promoted inhibition of DNA damage induced by CPA. Despite the chemoprevention observed, the clastogenicity/aneugenicity observed suggested caution about either continuous or high-dose usage of Rubus imperialis aerial parts extract by humans. [Copyright &y& Elsevier]

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. To evaluate the effects of M. robusta extract (HEMR) on colon and liver from mice with colitis induced by dextran sulfate sodium (DSS). 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. 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. 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. Image 1 [ABSTRACT FROM AUTHOR]