Isohemigossypolone: Antiophidic properties of a naphthoquinone isolated from Pachira aquatica Aubl.

We investigated the antiophidic properties of isohemigossypolone (ISO), a naphthoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities induced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting from the incubation of Pb with ISO in different concentrations (1:1, 1:5 and 1:10 w/w), we also evaluated the condition of treatment using ISO after 15 min of venom inoculation. The activities of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic induced by the B. pauloensis venom were significantly inhibited when the ISO was pre-incubated with the crude venom. For in vivo neutralization tests, the results were observed even when the ISO was applied after 15 min of inoculation of the venom or metalloprotease (BthMP). Also, to identify the inhibition mechanism, we performed in silico assays, across simulations of molecular coupling and molecular dynamics, it was possible to identify the modes of interaction between ISO and bothropic toxins BmooMPα-I, Jararacussin-I and BNSP-7. The present study shows that naphthoquinone isohemigossypolone isolated from the P. aquatica plant inhibited part of the local and systemic damage caused by venom proteins, demonstrating the pharmacological potential of this compound in neutralizing the harmful effects caused by snakebites.

Antiophidic activity of the secondary metabolite lupeol isolated from Zanthoxylum monogynum.

Previous studies have demonstrated the potential antiophidic activity of Zanthoxylum monogynum A.St.-Hil. a tree from the Rutaceae family native to South America. In this present contribution, we demonstrate the activity of the metabolite lupeol, a triterpenoid isolated from the stem bark of Z. monogynum against the harmful effects of the Bothrops alternatus venom. We investigated the antiophidic properties of lupeol, for this purpose, and use crude venom (Pb) incubated with lupeol in different concentrations, testing in vitro experiments and inoculated in mice for inhibitory evaluations in vivo. Besides, we tried to elucidate through the molecular dynamics the mechanism of action of lupeol with the bothropic thrombin-like toxin Jararacussin-I; the acidic phospholipase A2 toxin BthA-I from Bothrops jararacussu and the metalloproteinase toxin BmooMP-I from Bothrops moojeni. In our results, we demonstrated the potential inhibitory effect upon coagulant, phospholipasic and myotoxic activities of the bothropic venom, previously incubated with lupeol. We found that lupeol triterpenoid was able to partially inhibit local and systemic damage caused by snake venom toxins. Our in silico results demonstrate that lupeol is capable of interacting and altering the activity of the thrombin-like toxin Jararacussin-I, and capable of interacting with the BthA-I acidic PLA2, both toxins present in Bothrops snakes venom, thus demonstrating the pharmacological potential of this compound for the treatment of bothropic accidents.

Ethanolic Extract of the Fungus Trichoderma asperelloides Induces Ultrastructural Effects and Death on Leishmania amazonensis.

The Trichoderma genus comprises several species of fungi whose diversity of secondary metabolites represents a source of potential molecules with medical application. Because of increased pathogen resistance and demand for lower production costs, the search for new pharmacologically active molecules effective against pathogens has become more intense. This is particularly evident in the case of American cutaneous leishmaniasis due to the high toxicity of current treatments, parenteral administration, and increasing rate of refractory cases. We have previously shown that a fungus from genus Trichoderma can be used for treating cerebral malaria in mouse models and inhibit biofilm formation. Here, we evaluated the effect of the ethanolic extract of Trichoderma asperelloides (Ext-Ta) and its fractions on promastigotes and amastigotes of Leishmania amazonensis, a major causative agent of cutaneous leishmaniasis in the New World. Ext-Ta displayed leishmanicidal action on L. amazonensis parasites, and its pharmacological activity was associated with the low-molecular-weight fraction (LMWF) of Ext-Ta. Ultrastructural analysis demonstrated morphological alterations in the mitochondria and the flagellar pocket of promastigotes, with increased lipid body and acidocalcisome formation, microtubule disorganization of the cytoplasm, and intense vacuolization of the cytoplasm when amastigotes were present. We suggest the antiparasitic activity of Trichoderma fungi as a promising tool for developing chemotherapeutic leishmanicidal agents.

Effects of alkaloid extracts of mesquite pod on the products of in vitro rumen fermentation.

The objective of this study was to evaluate the effects of alkaloid extracts of Prosopis juliflora (Sw.) D.C. pods obtained by two extraction methods as compared with sodium monensin on the gas production kinetic, mitigation of methane, and rumen fermentation products using wheat bran or Tifton 85 hay as substrates, by the semi-automatic in vitro gas production technique. A completely randomized design was adopted, and two natural additives were tested made from mesquite pod (alkaloid extract I and alkaloid extract II) at three levels (3.9, 7.9, and 12 µg), sodium monensin 5 µM (positive control), and no inclusion of additives (negative control). The volume of gases produced by the degradation of the fibrous fraction of wheat bran was influenced by the concentration of the extract I added to the medium, and the amounts of 7.9 and 12 µg were equal to monensin at the lowest value. The degradation rate of the fibrous carbohydrates with additive extract I at 12 µg was lower in relation to monensin. When Tifton 85 hay was utilized, alkaloid extract I provided a shorter colonization time as compared with monensin at the added amounts of 7.9 and 12 µg and higher production of gases from the fibrous fraction but without interfering with the total volume of gases produced during 96 h of fermentation of carbohydrates. In the periods of 12 and 24 h of incubation, utilizing alkaloid extract I, the mean values of methane production with wheat bran and Tifton 85 hay were lower than monensin (p < 0.05) when the respective amounts of 7.9 and 12 µg were added. Alkaloid extract I has similar potential to sodium in reducing production of total gases, methane, and the acetate/propionate ratio.