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.

Biological and structural characterization of a new PLA(2) from the Crotalus durissus collilineatus venom

In the present article we report on the biological characterization and amino acid sequence of a new basic Phospholipases A(2) (PLA(2)) isolated from the Crotalus durissus collilineatus venom (Cdcolli F6), which showed the presence of 122 amino acid residues with a pI value of 8.3, molecular mass of 14 kDa and revealed an amino acid sequence identity of 80% with crotalic PLA(2)s such as Mojave B, Cdt F15, and CROATOX. This homology, however, dropped to 50% if compared to other sources of PLA(2)s such as from the Bothrops snake venom. Also, this PLA(2) induced myonecrosis, although this effect was lower than that of BthTx-I or whole crotoxin and it was able to induce a strong blockage effect on the chick biventer neuromuscular preparation, independently of the presence of the acid subunid (crotapotin). The neurotoxic effect was strongly reduced by pre-incubation with heparin or with anhydrous acetic acid and rho-BPB showed a similar reduction. The rho-BPB did not reduce significantly the myotoxic activity induced by the PLA(2), but the anhydrous acetic acid treatment and the pre-incu-bation of PLA(2) with heparin reduced significantly its effects. This protein showed a strong antimicrobial activity against Xanthomonas axonopodis passiflorae (Gram-negative), which was drastically reduced by incubation of this PLA(2) with rho-BPB, but this effect was marginally reduced after treatment with anhydrous acetic acid. Our findings here allow to speculate that basic amino acid residues on the C-terminal and molecular regions near catalytic site regions such as Calcium binding loop or rho-wing region may be involved in the binding of this PLA(2) to the molecular receptor to induce the neurotoxic effect. The bactericidal effect, however, was completely dependent on the enzymatic activity of this protein.

Preliminary cryocrystallography analysis of an eumenine mastoparan toxin isolated from the venom of the wasp Anterhynchium flavomarginatum micado

Mastoparans are tetradecapeptides found to be the major component of vespid venoms. These peptides present a wide spectrum of biological activities, such as mast cell degranulation, hemolytic activity and also reveals antimicrobial activity. A mastoparan toxin isolated from the venom of Anterhynchium flavomarginatum micado has been crystallized. At room temperature these crystals diffracted to 2.8 Angstrom resolution. However, upon cooling to cryogenic temperature around 85 K, the original resolution limit could be improved to 2.0 Angstrom. Crystals were determined to belong to the space group P3(1) (P3(2)). This is the first mastoparan to be crystallized and it will provide further insights in the conformational significance of mastoparan toxins, with respect to their potency and activity in G protein regulation. (C) 3001 Elsevier B.V. B.V. All rights reserved.