Walber Toma

Evaluation of the analgesic and antiedematogenic activities of Quassia amara bark extract.

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.

Mechanisms of action underlying the gastric antiulcer activity of the Rhizophora mangle L.

ETHNOPHARMACOLOGICAL RELEVANCE Rhizophora mangle, the red mangrove, has long been known as a traditional antiulcer medicine. The present work evaluated the mechanisms of action involved in the anti-ulcer properties of the Rhizophora mangle bark extracts. MATERIALS AND METHODS Gastroprotection of Rhizophora mangle was evaluated in rodent experimental models (ethanol). To elucidate the mechanisms of action the antisecretory action and involvement of NO, SH, mucus and PGE(2) were evaluated. The acetic acid-induced gastric ulcer model, Western blotting assay (COX-1, COX-2 and EGF) and immunohistochemical localization of HSP-70, PCNA and COX-2 were also used to evaluate the Rhizophora mangle healing properties. RESULTS Results showed that Rhizophora mangle bark crude extract (CE), as well as ethyl acetate (EtOAc) and butanolic fractions (BuOH) provided significant gastroprotection at all the tested doses. Thereby, the following protocols were performed using the lowest dose capable of producing the most effective gastroprotection, which was the BuOH 0.5mg/kg (P<0.001). Several mechanisms are involved in the antiulcer activity of Rhizophora mangle, such as, participation of NO, SH and mucus. The enhancement of PGE(2) levels and the upregulation of COX-2 and EGF seem to be directly linked to the antisecretory, cytoprotective and healing effects of BuOH. HSP-70 and PCNA are also involved in this cicatrisation process. No sign of toxicity was observed in this study, considering the analyzed parameters. CONCLUSION Our study reinforces its traditional medicinal use. Considering that the current therapies are based on the use of antisecretory or cytoprotective drugs, the Rhizophora mangle arises as a promising alternative antiulcer therapy.

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

Terminalia catappa L.: a medicinal plant from the Caribbean pharmacopeia with anti-Helicobacter pylori and antiulcer action in experimental rodent models.

ETHNOPHARMACOLOGICAL RELEVANCE Terminalia catappa L. (Combretaceae) is a medicinal plant listed as a pharmacopeia vegetable from Caribbean to treat gastritis. The objective of this study was to evaluate the gastroprotective and healing effect of the aqueous fraction (FrAq) obtained from the leaves of Terminalia catappa and to determine the antiulcer mechanism of action in experimental rodent models and its activity to Helicobacter pylori. MATERIAL AND METHODS In rodents, the FrAq was challenged by different necrotizing agents, such as absolute ethanol and ischemia-reperfusion injury. The antiulcer mechanism of action of FrAq was assessed and the healing effects of the fraction after seven and 14 days of treatment was evaluated by matrix metalloproteinase activity (MMP-2 and MMP-9). The toxicological effect of subacute treatment with FrAq during 14 days of treatment was also analyzed. The anti-Helicobacter pylori activity was determined by microdilution. The phytochemical study of the fraction was analyzed by experiments with FIA-ESI-IT-MS(n) (Direct Flow Analysis-ionization Electrospray Ion Trap Tandem Mass Spectrometry) and high performance liquid chromatography (HPLC) coupled to a photodiode array (PDA). RESULTS Oral treatment with FrAq (25mg/kg) significantly decreased the number of ulcerative lesions induced by ethanol and ischemia/reperfusion injury. The action of FrAq was mediated by the activation of defensive mucosa-protective factors, such as increases in mucus production, the nitric oxide (NO) pathway and endogenous prostaglandins. Oral treatment with FrAq for seven and 14 days significantly reduced the lesion area (80% and 37%, respectively) compared to the negative control group. Analyses of MMP-9 and MMP-2 activity from gastric mucosa confirmed the accelerated gastric healing effect of FrAq. This extract also presented considerable activity against Helicobacter pylori. The mass spectrum and MS/MS of the aqueous fraction indicates the existence of many different phenolic compounds, including punicalagin, punicalin, and gallagic acid, among others. CONCLUSIONS We concluded that FrAq from Terminalia catappa leaves has excellent preventive and curative effects on acute and chronic induced gastric ulcers and showed an important profile against Helicobacter pylori.

The gastroprotective effect of the essential oil of Croton cajucara is different in normal rats than in malnourished rats

It has been shown previously that malnourished rats are resistant to acute gastric lesions but not to subchronic gastric ulceration. It also has been demonstrated that the essential oil obtained from the bark of Croton cajucara (Sacaca) has antiulcer properties. In the present study, the ability of this essential oil to prevent the formation of gastric ulcers in rats fed a diet with 17% protein (normoproteic rats) or 6% protein (malnourished rats) was investigated. At a dose of 100 mg/kg body weight, orally, the essential oil significantly reduced the gastric injury caused by indomethacin (25% after 2 h and 70% after 4 h) only in normoproteic rats. In the pylorus ligature model, the essential oil increased the pH and gastric volume, but decreased the total acid concentration in both groups when compared to the respective control group. The essential oil significantly increased prostaglandin E2 production in glandular cells by 50% compared to the controls in both groups of rats. In addition, the amount of gastric mucus was two-fold higher in malnourished rats than in normoproteic rats. The present results show that the enhanced protective effect of essential oil in malnourished rats involved an increase in prostaglandin E2 production and mucus secretion, which are both factors that protect the gastric mucosa against damage. In agreement with this, malnourished rats always had a lower number of acute gastric ulcers.

Is gastric ulceration different in normal and malnourished rats

Protein malnutrition can adversely affect all tissues. The aim of the present study was to test the hypothesis that protein deprivation influences gastric ulcer formation, as well as metabolism and organ growth, in rats. In the present study, there was a significant reduction in the body and organ weight of rats fed a low-protein diet (P<0.001). Malnourished rats were less susceptible to ulceration of the gastric mucosa in ethanol and indomethacin models of acute gastric ulcers when compared with rats fed a normoproteic diet (17 % protein). Mucus production and prostaglandin E2 formation increased in malnourished rats, possibly explaining the lower number of acute ulcers in these animals. Pylorus ligature altered gastric juice composition (increased pH and gastric volume, and decreased total acid concentration) in the animal group fed a low-protein diet compared with the group fed a diet containing 17 % protein (P<0.05). The gastric mucosa was more damaged in malnourished rats than in normal rats evaluated for 14 d after acetic acid injection (P<0.001). Malnourished rats exhibited resistance to acute gastric lesions, owing to an increase in prostaglandin GE2 release and mucus secretion, which protected their gastric mucosa. This phenomenon was not seen in subchronic gastric ulceration.

The antiulcer effect of Croton cajucara Benth in normoproteic and malnourished rats.

The aim of the present study is to investigate the antiulcerogenic effects of the essential oil (EO) of Croton cajucara Benth in rats fed with a normal protein (NP) and low-protein diet (MN). NP and MN rats were treated with the essential oil for 15 days after chronic ulceration was induced. The EO accelerated healing of acetic acid-induced gastric lesions in NP and MN rats (p<0.05). In a similar experiment on chronic ulceration, Epidermal Growth Factor (EGF) mRNA expression increased in NP rats but not in MN rats. In assays of acute antiulcerogenic activity, C. cajucara increased somatostatin plasma levels and decreased gastrin plasma levels in both animal groups. The EO significantly prevented ethanol-induced gastric ulcers in NP and MN rats (p<0.001). Histological examination showed initial regeneration, formation of inflammatory infiltrate and angiogenesis in the epithelium surface of acetic acid-induced ulcers in NP and MN rats. C. cajucara prevented gastric lesions in both animal groups when ethanol methodology was used. We concluded that the EO showed an antiulcerogenic activity mediated by increased somatostatin secretion and EGF mRNA expression.

Multivariate Method Based on Raman Spectroscopy for Quantification of Dipyrone in Oral Solutions

This work employed a quantitative model based on Raman spectroscopy and principal component regression (RS/PCR) to quantify the active ingredient dipyrone (metamizole) in commercially available formulations as an analytical methodology for quality control in the pharmaceutical industry. Raman spectra were collected using a dispersive Raman spectrometer (830 nm, 250 mW excitation, and 20 s exposure time) coupled to a Raman probe. Solutions of dipyrone diluted in water in the range of 80 to 120% of the concentration of commercial formulations (500 mg/mL) were used to develop a calibration model based on PCR to obtain the figures of merit for class I validation from the Brazilian Sanitary Surveillance Agency (ANVISA, RE no. 899/2003). This spectral model was then used to predict the concentration of dipyrone in commercial formulations from distinct brands with 500 mg/mL. A prediction error of 6.5 mg/mL (1.3%) was found for this PCR model using the diluted samples. Commercial formulations had predicted concentrations with a difference below 5.0% compared to the label concentration, indicating the applicability of Raman spectroscopy for quality control in the final product.