Gastrointestinal effects of Mentha aquatica L. essential oil.

Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect (> 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD.

Spilanthol, the Principal Alkylamide from Acmella oleracea, Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice.

Mucositis is one of the commonest side effects in cancer patients undergoing treatment with radiotherapy and/or chemotherapy, and it currently lacks appropriate and effective treatment. Acmella oleracea, a species of flowering herb from South America, contains spilanthol, an alkylamide that has several pharmacological properties, including anesthetic, analgesic, and anti-inflammatory activities. Therefore, the purpose of this work was to evaluate the effect of spilanthol in intestinal mucositis in Swiss mice induced by 5-fluorouracil (5-FU), an antineoplastic agent administered systemically for the treatment of many different cancers. The repeated administration of 5-FU resulted in intestinal mucositis and consequent decreased food intake, together with weight loss, in all the animals. Daily administration of spilanthol significantly lowered the severity of intestinal mucositis, reducing histopathological changes and increasing the villus height in the animals treated with spilanthol at a dosage of 30 mg/kg (p < 0.0044) compared to a group exposed only to 5-FU. A decrease of myeloperoxidase activity was also observed in the animals treated with 30 mg/kg of spilanthol (p < 0.05), although several pro-inflammatory cytokines were not quantifiable in any group. In conclusion, the data demonstrated that spilanthol effectively reduced inflammation in a mouse model of intestinal mucositis induced by 5-FU, and that the compound might be a promising therapeutic candidate for the prevention and treatment of this condition.

Antiulcerative and Antinociceptive Activities of Casein and Whey Proteins.

The aim of this study was to evaluate the antiulcerative and antinociceptive activities of milk proteins using the induced gastric ulcer with ethanol rat model and the acetic acid-induced writhing mouse model. Casein (CN), (100, 300, and 1000 mg kg-1) doses presented antiulcerative activity on a dose-dependent manner with values of 30.8%, 41.4%, and 57.0% of inhibition measured using the ulcerative lesions index (ULI), respectively. Whey protein concentrate (WPC), (100, 300, and 1000 mg kg-1) doses presented antiulcerative activity on a dose-dependent manner with values of 48.9%, 65.5%, and 68.22% of ULI inhibition, respectively. CN, casein hydrolysates (CNH), WPC, and whey protein hydrolysates (WPH), (3, 10, and 30 mg kg-1) doses presented antinociceptive activity using the acetic acid-induced writhing in the mouse model. CN (30 mg kg-1) presented a value of 40% of inhibition writhing, and CNH (30 mg kg-1) presented antinociceptive activity with a value up to 46% of writhing inhibition. WPC (30 mg kg-1) presented a value of 52.50%, and WPH (30 mg kg-1) presented antinociceptive activity with a value up to 88.00% of writhing inhibition. In conclusion, CN and WPC demonstrated in vivo antiulcerative properties and represent a promising alternative to be used as protectors of the gastric mucosa. CNH and WPH demonstrated in vivo antiulcerative properties and represent a promising alternative to be used as natural analgesic.

Antiulcerative Activity of Milk Proteins Hydrolysates.

Several studies have shown the protective effect of dairy products, especially α-lactalbumin and derived hydrolysates, against induced gastric ulcerative lesions. The mucus strengthening represents an important mechanism in the defense of gastrointestinal mucosa. Previously, a hydrolysate from casein (CNH) and a hydrolysate from whey protein concentrate rich in ß-lactoglobulin (WPH) demonstrated a stimulatory activity on mucus production in intestinal goblet cells. The aim of this work was to evaluate the possible antiulcerative activity of these two hydrolysates in an ethanol-induced ulcer model in rats. All tested samples significantly reduced the ulcerative lesions index (ULI), compared with the saline solution, using doses of 300 and 1000 mg kg-1 body weight with decreases up to 66.3% ULI. A dose-response relationship was found for both hydrolysates. The involvement of endogenous sulfhydryl (SH) groups and prostaglandins (PGs) in the antiulcerative activity was evaluated using their blockage. The antiulcerative activity of WPH showed a drastic decrease in presence of N-ethylmaleimide (from 41.4% to 9.2% ULI). However, the CNH antiulcerative properties were not significantly affected. The cytoprotective effect of WPH appears to depend on a PG-mediated mechanism. In conclusion, CNH and WPH demonstrated in vivo antiulcerative properties and represent a promising alternative as protectors of the gastric mucosa.

Phytochemical Analysis and Antifungal Activity of Extracts from Leaves and Fruit Residues of Brazilian Savanna Plants Aiming Its Use as Safe Fungicides.

The increasing demand for safe food without preservatives or pesticides residues has encouraged several studies on natural products with antifungal activity and low toxicity. In this study, ethanolic extracts from leaves and fruit residues (peel and seeds) of three Brazilian savanna species (Acrocomia aculeata, Campomanesia adamantium and Caryocar brasiliense) were evaluated against phytopathogenic fungi. Additionally, the most active extract was chemically characterized by ESI-MS and its oral acute toxicity was evaluated. Extracts from C. brasiliense (pequi) peel and leaves were active against Alternaria alternata, Alternaria solani and Venturia pirina with minimal inhibitory concentrations between 350 and 1000 µg/mL. When incorporated in solid media, these extracts extended the lag phase of A. alternata and A. solani and reduced the growth rate of A. solani. Pequi peel extract showed better antifungal activity and their ESI-MS analysis revealed the presence of substances widely reported as antifungal such as gallic acid, quinic acid, ellagic acid, glucogalin and corilagin. The oral acute toxicity was relatively low, being considered safe for use as a potential natural fungicide.

Chitosan-tripolyphosphate nanoparticles as Arrabidaea chica standardized extract carrier: synthesis, characterization, biocompatibility, and antiulcerogenic activity.

Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.

Gastroprotective effects of goniothalamin against ethanol and indomethacin-induced gastric lesions in rats: Role of prostaglandins, nitric oxide and sulfhydryl compounds.

Goniothalamin (GTN), a styryl-lactone, is a secondary metabolite naturally found in its enantiomeric form (R) in plants of the genus Goniothalamus (Annonaceae). The antiproliferative activity against human tumor cell lines reported in several studies suggest that the α,ß-unsaturated δ-lactone moiety emerges as a key Michael acceptor for cysteine residues or other nucleophilic biological molecules. Our group reported on the in vivo activity of (R)- and (S)-GTN as well as its racemic form (rac-GTN) in both Ehrlich solid tumor and carrageenan-induced paw edema in mice, without side effects in the effective doses. Despite the rich body of data on the in vitro GTN biological activity, much less is known about its in vivo pharmacological action. Herein we describe the gastroprotective activity of rac-GTN on chemical-induced gastric ulcers models in rats. GTN has a potent gastroprotective effect on ethanol-induced ulcers (effective dose50=18mg/kg) and this activity is dependent on sulfhydryl compounds and prostaglandins generation, but independent of nitric oxide (NO), gastric secretion and mucus production. We hypothesize that goniothalamin may act as a mild irritant, inducing the production of sulfhydryl compounds and prostaglandins, in a process known as adaptive cytoprotection. This hypothesis is supported by the fact that Michael acceptors are the most potent inducers of antioxidant response (as activation of Nrf2 pathway) through generation of mild oxidative stress and that gastroprotective activity of goniothalamin is inhibited after pre-treatment with NEM (N-ethylmaleimide) and NSAID (non-steroidal anti-inflammatory drugs), highlighting the importance of sulfhydryl compounds and prostaglandins on GTN activity.

Atividade antiulcerogênica e mecanismo de ação de alimento fermentado à base de trigo e soja utilizado como alimento funcional / Antiulcer activity and mechanism of action of fermented food based on wheat and soy beans used as functional food

Objetivo: estudar o mecanismo de ação e avaliar a proteção da mucosa do estômago de ratos Wistar pela atividade de um alimento com propriedades funcionais à base de trigo e soja fermentado, a fim de reduzir o processo ulcerativo induzido por etanol. Métodos: nesse estudo foram utilizados os modelos de indução de úlcera por etanol absoluto em ratos Wistar tratadospreviamente com Indometacina (5mg/kg de peso), N-etilmaleimida (10mg/kg de peso) e L-NAME (5mg/kg de peso). No mesmo modelo de indução de úlcera foi realizada a administração de solução salina (10mL/kg de peso) como controle negativo, Carbenoxolona (200mg/kg) como controle positivo e o produto fermentado na dose de 2000mg/kg de peso animal. Resultados: na verificação da atividade antiulcerogênica do fermentado em pó, o Índice de Lesões Ulcerativas (ILU) foi inibido em 29,9%, enquanto a Carbenoxolona utilizada como controle positivo foi capaz de inibir o ILU em 83,7%. No modelo de indução de úlcera por etanol absoluto, com a administração prévia de L-NAME, N-etilmaleimida e da Indometacina, constatou-se que, nos dois primeiros tratamentos, o fermentado apresentou atividade antiulcerogênica de 50,9% e 28,3%, respectivamente e no tratamento com Indometacina, o produto não apresentou atividade antiulcerogênica, o que sugere que seu mecanismo de ação ocorre pela síntese ou redução da degradação de prostaglandinas que são uma das responsáveis pela citoproteção gástrica. Conclusão: com base nos dados obtidos nesse experimento com ratos para avaliação da atividade antiulcerogênica e mecanismo de ação do produto fermentado, concluiu-se que este provavelmente promove a citoproteção gástrica especialmente através dos níveis de prostaglandinas.

Objective: to study the mechanism of action and evaluate the protection of the stomach mucosa of Wistar rats due to the activity of a fermented soy and wheat-based food product with functional properties in order to reduce the ethanol-induced ulcerative process. Methods: in this study, ulcer induction models by absolute ethanol were used in Wistar rats previously treated with Indomethacin (5mg/kg of body weight), N-ethylmaleimide (10mg/kg of body weight), and L-NAME (5mg/kg of body weight). Within the same ulcer induction model, the administration of the following was performed: saline solution (10 mL/kg of body weight) as a negative control, Carbenoxolone (200mg/kg) as a positive control, and the fermented product at a dose of 2,000mg/kg of body weight. Results: when verifying the antiulcerogenic activity of the fermented powder, the Ulcerative Lesion Index (ULI) was inhibited by 29.9%, while the Carbenoxolone used as a positive control was able to inhibit the ULI by 83.7%. In the ulcer induction model by absolute ethanol, with previous administration of L-NAME, N-ethylmaleimide, and Indomethacin, it was verified that with the first two treatments the fermented powder showed 50.9% and 28.3% antiulcerogenic activity, respectively, and no antiulcerogenic activity with the Indomethacin treatment, which suggests that its mechanism of action occurs through the synthesis or degradation reduction of prostaglandins responsible, along with other factors, for the gastric cytoprotection. Conclusion: based on the data from this trial with rats to evaluate the antiulcerogenic activity and mechanism of action of the fermented product, it was concluded that it probably promotes gastric cytoprotection, mainly through prostaglandin levels.