Evaluation of the gastroprotective and ulcer healing properties by Fridericia chica (Bonpl.) L.G. Lohmann hydroethanolic extract of leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Fridericia chica (Bonpl.) L.G. Lohmann (Bignoniaceae), is a climber native to Brazil, found in all Brazilian biomes. It is mostly known in Brazil as "carajiru," and home medicines made from the leaves have been used to cure disorders including stomach ulcers and other gastrointestinal disorders. AIM OF THE STUDY: The objective of the study was to investigate the F. chica hydroethanolic extract of leaves (HEFc) preventative and curative antiulcer gastrointestinal efficacy as well as the mechanisms of action using in vivo rodent models. MATERIALS AND METHODS: F. chica was collected in the municipality of Juína, Mato Grosso, and its leaves were used to prepare the extract by maceration technique (70% hydroethanol in the 1:10 ratio, w/v) to obtain the HEFc. The chromatographic analysis of HEFc was carried out by High Performance Liquid Chromatography-Photo Diode Array-Electrospray Ionization-Mass Spectrometry (HPLC-PDA-ESI-MS)- LCQ Fleet™ system. To determine the potential antiulcer potential of HEFc (1, 5 and 20 mg/kg, p.o.), the gastroprotective activity was assessed in various animal models of stomach ulcers caused by acidified ethanol, water constraint stress, indomethacin, (acute), and acid acetic (chronic). Additionally, the prokinetic properties of the HEFC were assessed in mice. The gastroprotective underlying mechanisms were evaluated by the histopathological analysis and determination of gastric secretion (volume, free and total acidity), gastric barrier mucus, activation of PGs, NO, K +ATP channels, α2-adrenoceptor, antioxidant activity (GSH, MPO and MDA), NO and mucosal cytokines (TNF-α, IL-1ß, and IL-10) levels. RESULTS: The chemical composition of HEFc was analyzed and apigenin, scutellarin, and carajurone were identified. HEFc (1, 5 and 20 mg/kg) showed effect against acute ulcers induced by HCl/EtOH with a reduction in the ulcerated area of 64.41% (p < 0.001), 54.23% (p < 0.01), 38.71% (p < 0.01), respectively. In the indomethacin experiment, there was no change in the doses tested, whereas in the water immersion restraint stress ulcer there was a reduction of lesions at doses of 1, 5, and 20 mg/kg by 80.34% (p < 0.001), 68.46% (p < 0.01) and 52.04% (p < 0.01). HEFc increased the mucus production at doses of 1 and 20 mg/kg in 28.14% (p < 0.05) and 38.36% (p < 0.01), respectively. In the pyloric ligation-induced model of gastric ulceration, the HEFc decreased the total acidity in all doses by 54.23%, 65.08%, and 44.40% (p < 0.05) and gastric secretory volume in 38.47% at dose of 1 mg/kg (p < 0,05) and increased the free acidity at the dose of 5 mg/kg by 11.86% (p < 0.05). The administration of EHFc (1 mg/kg) showed a gastroprotective effect possibly by stimulating the release of prostaglandins and activating K+ATP channels and α2-adrenoreceptors. Also, the gastroprotective effect of HEFc involved an increase in CAT and GSH activities, and a reduction in MPO activity and MDA levels. In the chronic gastric ulcer model, the HEFc (1, 5 and 20 mg/kg) decreased the ulcerated area significantly (p < 0.001) at all doses by 71.37%, 91.00%, and 93.46%, respectively. In the histological analysis, HEFc promoted the healing of gastric lesions by stimulating the formation of granulation tissue and consequently epithelialization. On the other hand, regarding the effect of HEFc on gastric emptying and intestinal transit, it was observed that the extract did not alter gastric emptying, but there was an increase in intestinal transit at the dose of 1 mg/kg (p < 0.01). CONCLUSION: These outcomes confirmed the advantages of Fridericia chica leaves for the treatment of stomach ulcers, which are well-known. HEFc was discovered to have antiulcer characteristics through multitarget pathways, which might be related to an increase in stomach defense mechanisms and a decrease in defensive factor. HEFc can be regarded as a potential new antiulcer herbal remedy because of its antiulcer properties, which may be attributed to the mixture of flavonoids, apigenin, scutellarin and carajurone.

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats.Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model.Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses.Stool samples were collected and processed for analysis of the short-chain fatty acid.Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation.Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Therapeutical properties of Mimosa caesalpiniifolia in rat liver intoxicated with cadmium.

The aim of this study was to evaluate the therapeutic properties of Mimosa caesalpiniifolia in liver of rats exposed to cadmium under morphological, oxidative, inflammatory, and mutagenic parameters. A total of 40 Wistar rats (90 days, ~ 250 g) were distributed into eight groups (n = 5) as follows: (i) control; (ii) cadmium: cadmium chloride injection at 1.2 mg/kg; (iii) Mimosa extract: treatment with Mimosa extract at 250 mg/kg; (iv) Mimosa fraction: treatment with Mimosa acetate fraction at 62.5 mg/kg; (v) cadmium and Mimosa extract 62.5: submitted to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 62.5 mg/kg; (vi) cadmium and Mimosa extract 125: subjected to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 125 mg/kg; (vii) cadmium and Mimosa 250 extract: submitted to cadmium chloride 1.2 mg/kg injection and treatment with Mimosa extract at 250 mg/kg; (viii) cadmium treated with fraction of Mimosa acetate: submitted to cadmium chloride 1.2 mg/kg injection and treatment with acetate fraction of Mimosa extract at 62.5 mg/kg. In the animals intoxicated with cadmium and treated with fraction [62.5], increased expression of SOD-Mn reduced frequency of binucleated hepatocytes, karyolysis, and karyorrhexis, besides the antimutagenic and antioxidant action. The extract [62.5] was cytoprotective, antimutagenic, and reduced karyolysis. The extract [125] was cytoprotective, antioxidant, antifibrotic, anti-inflammatory, and reduced frequency of binucleated hepatocytes, while extract [250] was cytotoxic and mutagenic. In summary, the extract of Mimosa exerts some therapeutic properties in hepatic tissue after Cd intoxication, but only when it is administrated at intermediate doses. Probably, a high content of polyphenols in the EHM [250] and Fr-EtOAc groups exert pro-oxidant activities in the liver particularly when associated with Cd.

Evaluation of the Chemopreventive Activity of Grape Skin Extract Using Medium-term Oral Carcinogenesis Assay Induced by 4-Nitroquinoline 1-Oxide.

BACKGROUND/AIM: The aim of this study was to evaluate the chemoprotective potential of grape skin extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). MATERIALS AND METHODS: Male Wistar rats were distributed into four groups (n=5, per group): Control Group: free access to commercial diet and drinking water for 12 weeks; 4NQO Group: received 4NQO diluted in drinking water daily, for 12 weeks; Grape Skin Extract Group: free access to water and received grape skin extract incorporated with diet for 12 weeks; 4NQO + Grape Skin Extract Group: received 4NQO in drinking water daily and grape extract incorporated with diet for 12 weeks. RESULTS: Animals treated with grape skin extract revealed a significant reduction in epithelial dysplasia. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and ki-67 immunoexpression was reduced in animals treated with grape skin extract. Western blot analysis showed a significant decrease of p-NFκB p50 and MyD88 protein expression in the groups treated with grape skin extract. Copper-zinc superoxide dismutase, manganese superoxide dismutase, and catalase gene expression did not present any statistically significant differences (p>0.05). CONCLUSION: Grape skin extract displayed chemopreventive activity in oral carcinogenesis assays as depicted by its antioxidant, anti-proliferative and anti-inflammatory properties.

Protective effects of purple carrot extract (Daucus carota) against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

The aim of this study was to evaluate the chemopreventive potential of purple carrot extract following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). For this purpose, histopathological analysis, proliferative status, antioxidant activity and inflammatory status were investigated in this setting. A total of 20 male rats were distributed into four groups as follows (n = 5 per group): Group 1-free access to water and commercial diet for 12 weeks; Group 2-received 4NQO at 50 ppm dose in drinking water daily and commercial diet for 12 weeks; Group 3-free access to water and received diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks; and Group 4-received 4NQO at 50 ppm dose in drinking water daily and diet supplemented with purple carrot extract (0.1 g/kg) for 12 weeks. Histopathological analysis revealed that animals treated with purple carrot extract reduced the oral lesions such as dysplasia and squamous cell carcinoma. Animals with oral pre-neoplastic lesions and treated with purple carrot extract decreased ki-67 and 8-OHdG immunoexpression. Moreover, pNFκBp50 and MyD88 protein expressions were decreased after purple carrot treatment associated or not with 4NQO exposure. SOD-Mn mRNA levels increased with treatment with purple carrot extract as well. In conclusion, our results demonstrated that purple carrot extract was able to protect oral lesions induced by 4NQO in Wistar rats as a result of antioxidant activity, anti-inflammatory potential and antiproliferative and antimutagenic actions.

The Anti-Inflammatory Potential of Mimosa caesalpiniifolia Following Experimental Colitis: Role of COX-2 and TNF-Alpha Expression.

The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 - Sham group:; G2 - TNBS group; G3, G4 -colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 - colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.

Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats.

The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity.

Avaliação da atividade antioxidante e antimicrobiana dos extratos e frações orgânicas de Mimosa caesalpiniifolia Benth. (Mimosaceae) / Assessment of the antioxidant and antimicrobial activity of the organic extracts and fractions of Mimosa caesalpiniifolia Benth. (Mimosaceae)

A espécie Mimosa caesalpiniifolia Benth. (Mimosaceae), conhecida popularmente como sabiá e cerva viva, é uma planta arbórea encontrada na caatinga nordestina brasileira, amplamente utilizada pela população na forma de infusões para o tratamento de feridas, bronquites e anti-inflamatório. Diante do exposto, os objetivos deste estudo, foram determinar as atividades antioxidantes e antimicrobianas do extrato etanólico das folhas (EHM), caules (EHL), cascas do caule (EHC), raízes (EHR) e frações obtidas das folhas de M. caesalpiniifolia Benth. A atividade antioxidante foi avaliada através do método de captação do radical DPPH, enquanto a atividade antimicrobiana foi avaliada pelo método de microdiluição em caldo, sobre leveduras, bactérias Gram-positivas e Gram-negativas. A capacidade antioxidante mostrou que a fração acetato de etila (Fr-EtOAc) foi diretamente proporcional ao teor de polifenóis totais com IC50 de 20,08 ± 0,10 ?g/mL e 721,29±0,60 mg de EAG (equivalentes de ácido gálico) por g de extrato. Na atividade antimicrobiana, todos os extratos e frações exibiram atividade inibitória de crescimento frente aos micro-organismos microrganismos avaliados e em concentrações variando de 5 a 1000 ?g/mL. A Fr-EtOAc apresentou valores promissores de inibição de crescimento frente a fungos, como Candida glabrata (ATCC 90030) e Candida krusei (ATCC 6258), com concentrações de 20 e 40 ?g/mL, respectivamente. Estes resultados são importantes, pois são os primeiros a serem realizados com a espécie M. caesalpiniifolia.

The species Mimosa caesalpiniifolia Benth. (Mimosaceae), popularly known as thrush and hind alive, is a tree found in Brazilian caaringa, widely used by the population in the form of infusions for the treatment of wounds, bronchitis and anti-inflammatory. Thus, the goal of this study was to determine the antioxidant and anti-microbial activity of ethanolic extracts from the leaves (EHM), trunks (EHL), trunk barks (EHC), roots (EHR) and fractions obtained from the leaves of M. caesalpiniifolia Benth., used by the populations as popular medication as an anti-inflammatory medication and as a relief to respiratory problems. The antioxidant action was evaluated through the capturing the radical DPPH, while the antimicrobial action was evaluated through the method of micro-dilution in broth, on yeasts, Gram-positive and Gram-negative bacteria. The antioxidant capacity has shown that the ethyl-acetate fraction (Fr-EtOAc) was directly proportional to the poly-phenol contents with an IC50 at 20.08 ± 0,10?g/ mL and 721.29±0.60mg of EAG (gallic acid equivalents) per g of the extract. As regards the antimicrobial activity, the extracts and fractions showed a growth-inhibiting activity for the micro-organisms evaluated and in concentrations from 5 to 1000?g/mL. The Fr-EtOAc showed promising growth-inhibiting figures in the case of yeasts such as Candida glabrata (ATCC 90030) and Candida krusei (ATCC 6258), in 20 and 40?g/mL concentrations, respectively. These results are important as they are the first to be obtained with the M. Caesalpiniifolia species.

Antinociceptive effect of the extract of Morus nigra leaves in mice.

Morus nigra has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of dichloromethane extract from leaves of M. nigra. The formalin, hot plate, and tail immersion tests as well as acetic acid-induced writhing were used to investigate the antinociceptive activity in mice. The extract at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. The extract administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.), which supports previous claims for its traditional use.