Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst of Helicobacter pylori

Ten Brazilian medicinal plants used to treat gastritis and ulcers were carefully selected on the basis of ethnopharmacological importance and antiulcerogenic activity previously described. The antioxidant activity of the methanolic extracts was determined in analysis conditions that simulate a real biological activity on inhibition of the oxidative burst induced in neutrophils using Helicobacter pylori as activator, by a luminol-amplified chemiluminescence assay. The extracts, at low concentration (5 μg/mL), exhibited a large variation in inhibitory effects of H. pylori-induced oxidative burst ranging from 48% inhibition to inactive, but all extracts, excluding Byrsonima intermedia, had inhibitory activity over 80% at the concentration of 100 μg/mL. The total suppressive antioxidant capacity measured as the effective concentration, which represents the extract concentration producing 50% inhibition of the chemiluminescence induced by H. pylori, varies from 27.2 to 56.8 μg/mL and was in the following order: Qualea parviflora > Qualea multiflora > Alchornea triplinervia > Qualea grandiflora > Anacardium humile > Davilla elliptica > Mouriri pusa > Byrsonima basiloba > Alchornea glandulosa > Byrsonima intermedia. The main groups of compounds in tested extracts are presented. Differences in the phytochemical profile, quantitatively and qualitatively, of these plants can explain and justify their protective effect on the gastric mucosa caused by the neutrophil-generated ROS that occurs when H. pylori displays its evasion mechanisms

Anti-Helicobacter pylori effect of the antioxidant extract from Baccharis trimera Less. (DC)

One of the main risk factors for the development of stomach ulcers and cancer is infection with Helicobacter pylori bacteria, which is accompanied by considerable oxidative stress. Therefore, the aim of the present study was to assess the anti-Helicobacter pylori activity of B. trimera hydroalcoholic extract (HE) and aqueous (AqF), hexanic (HxF), and acetonitrile/chloroform (ACF) fractions, as well as their oxidant potentials.A preliminary phytochemical screening was carried out. Anti-Helicobacter pylori activity was assessed using a microdilution assay. After exposure to the investigated samples, the bacterial morphology was analysed under a scanning electron microscope (SEM). The antioxidant activity was evaluated in hydrogen peroxide (H 2 O 2 ), superoxide anion (O 2 •- ), hypochlorous acid (HOCl), hydroxyl radical (HO • ) and nitric oxide (NO • ) assays.The highest concentration of polyphenols was found in HE, the highest   concentration of flavonoids was found in ACF, and of tannins was found in AqF. In the anti-H. pylori assay, the MIC 90 was 512 µg/mL for HE and 1024 µg/mL for ACF, which was bactericidal. The SEM showed morphological alterations such as cell lysis in the tested samples. In the O 2 •- inhibition assay, the EC 50 of AqF was 5.85 ± 0.86. In the HOCl, HO • radical, NO • and H 2 O 2 scavenging assays, the best results were in ACF, with an EC 50 of 15.50 ± 0.80, 2.90 ± 0.48, 132.13 ± 7.38 and 66.70 ± 2.30 µg/mL, respectively. The analyses indicate that compounds present in B. trimera, especially in HE and ACF, are promising candidates for the prevention and treatment of diseases caused by H. pylori

Anti-Helicobacter pylori activity and oxidative burst inhibition by the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

Helicobacter pylori is a bacterium recognized as the major cause of chronic gastritis and peptic ulcers. Infection by H. pylori induces inflammatory responses and pathological changes in the gastric microenvironment. The host Keywords: immune cells (especially neutrophils) release inflammatory mediators and large 5-methoxy-3,4-dehydroxanthomegnin amounts of reactive oxygen species (ROS), which are associated with an increased Helicobacter pyloririsk of developing gastric cancer. In this study, we evaluated the anti-H. pylori and oxidative burst antioxidantactivitiesofa1,4-naphthoquinone-5-methoxy-3,4-dehydroxanthomegnin. Paepalanthus latipes The antimicrobial activity was assessed using a spectrophotometric microdilution technique, and antioxidant activity was assessed by noting the effect of 5-methoxy3,4-dehydroxanthomegnin on the neutrophil oxidative burst using luminol-and lucigenin-amplified chemiluminescence. The results showed that 5-methoxy-3,4dehydroxanthomegnin is a potent anti-H. pylori compound (MIC 64 µg/mL and MBC 128 µg/mL) and a strong antioxidant. 5-Methoxy-3,4-dehydroxanthomegnin decreased luminol- and lucigenin-amplified chemiluminescence, with ED50 values of 1.58±0.09 µg/mL and 5.4±0.15 µg/mL, respectively, reflecting an inhibitory effect on the oxidative burst. These results indicate that 5-methoxy-3,4-dehydroxanthomegnin is a promising compound for the prevention and treatment of diseases caused by H. pylori infection, such as gastritis, peptic ulceration, and gastric cancer, because reactive oxygen intermediates are involved in the pathogenesis of gastric mucosal injury induced by H. pylori infections.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Preformulation study and influence of DMSO and propylene glycol on the antioxidant action of isocoumarin paepalantine isolated from Paepalanthus bromelioides

Coumarins are phenolic compounds and have various biological properties, including antioxidant activity. The isocoumarin paepalantine, isolated from of Paepalanthus bromelioides Silveira, Eriocaulaceae, exhibits a wide range of biological activities, including antimicrobial, anti-inflammatory, antioxidant and cytotoxic properties. Studies on paepalantine often use dimethylsulfoxide as a solvent. However the dimethylsulfoxide interferes with antimicrobial, cytotoxic and antioxidant assays. Thus, this study aims to evaluate alternative solvents for paepalantine and evaluate their potential to interfere with antioxidant assays (ABTS·+, O2·−, HOCl). Of the selected solvents, propylene glycol had good solubility and remained stable throughout the study period. The results suggested that there is no interference from propylene glycol in antioxidant assays, while dimethylsulfoxide significantly interfered with the HOCl assay. The antioxidant assays showed that paepalantine demonstrated similar or even better antioxidant activity than Trolox. Thus, propylene glycol may be the solvent of choice for paepalantine, a compound that has significant biological potential. Keywords: Antioxidant, Paepalantine, Preformulatio

The triad indole-3-acetic acid ethyl ester/esterase/horseradish peroxidase as a new cytotoxic prodrug/enzyme combination

The antibody-directed enzyme prodrug therapy (ADEPT) is a means of restricting the action of toxic drugs to the tumor site. The enzyme/prodrug pair horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) has been studied as a combination with potential application in ADEPT strategies. In this combination, the non-toxic plant hormone IAA is activated to cytotoxic species by the catalytic action of HRP. Objective: We studied the use of the ethyl ester of IAA as a new prodrug that could be activated by two enzymes, HRP and esterase. Methods: The oxidation of IAA and its ethyl ester, catalyzed by HRP, was monitored by the consumption of dioxygen and liquid chromatography. The cytotoxicity of IAA and its ethyl ester in combination with HRP and esterase was assessed using the lineage McCoy cells through the trypan blue and neutral red assays. Results: We found that HRP was not able to catalyze the oxidation of IAA-ethyl ester in the absence of an additional esterase. Hence, the potential cytotoxicity of the IAA-ethyl ester could be controlled by sequential treatment with esterase, to liberate the carboxyl group, and HRP, for oxidation and generation of cytotoxic species. We present evidence for the potential application of the combination IAA-ethyl ester/esterase/horseradish peroxidase as a new ADEPT, GDEPT or related strategy. Conclusions: We suggest that this technique could provide more selectivity in the generation of cytotoxic drugs at tumor sites.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Inhibition of Nitric Oxide and Tumour Necrosis Factor-α Production in Peritoneal Macrophages by Aspergillus nidulans Melanin

The naturally occurring pigment, melanin is found in organisms of all phylogenetic kingdoms, including fungi, and exhibits a wide range of biological activities. Our objective was to investigate the effects of melanin extracted from the fungus Aspergillus nidulans on the production of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) in peritoneal macrophages and on the viability of McCoy mouse fibroblasts. The results showed that A. nidulans melanin did not stimulate NO production in macrophages, but it inhibited the NO production in lipopolysaccharide (LPS)-stimulated macrophages by approximately 82%. Similarly, A. nidulans melanin inhibited LPS-stimulated TNF-alpha production by 52% and showed a slight stimulatory effect on TNF-alpha production in macrophages. In addition, the toxicity of A. nidulans melanin to McCoy cells was much lesser (IC50=373.5 +/- 2.4 mu g/mL) than that of known agents such as cisplatin (IC50=41.2 mu g/mL). The viability of peritoneal macrophages was greater than 90% at the highest melanin concentration tested (100 mu g/mL). Thus, the combination of low cytotoxicity and marked inhibition of TNF-alpha and NO production suggests that A. nidulans melanin has potential as an anti-inflammatory agent and may be used in the future for development of new drugs with therapeutic utility

In Vitro and In Silico Evaluation of Red Algae <i>Laurencia obtusa</i> Anticancer Activity

Studies estimate that nearly 2 million new cases of gastric cancer will occur worldwide during the next two decades, which will increase mortality associated with cancer and the demand for new treatments. Marine algae of the Laurencia genus have secondary metabolites known for their cytotoxic action, such as terpenes and acetogenins. The species Laurencia obtusa has demonstrated cytotoxicity against many types of tumors in previous analyses. In this study, we determined the structure of terpenes, acetogenins, and one fatty acid of Laurencia using mass spectrometry (ESI-FT-ICR/MS). In vitro cytotoxicity assays were performed with adenocarcinoma gastric cells (AGS) to select the most cytotoxic fraction of the crude extract of L. obtusa. The Hex:AcOEt fraction was the most cytotoxic, with IC50 9.23 µg/mL. The selectivity index of 15.56 shows that the Hex:AcOEt fraction is selective to cancer cells. Compounds obtained from L. obtusa were tested by the analysis of crystallographic complexes. Molecular docking calculations on the active site of the HIF-2α protein showed the highest affinity for sesquiterpene chermesiterpenoid B, identified from HEX:AcOEt fraction, reaching a score of 65.9. The results indicate that L. obtusa presents potential compounds to be used in the treatment of neoplasms, such as gastric adenocarcinoma