Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

The development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.Portuguese FCT CCMAR/Multi/04326/2013FAPESP [2013/16297-2, 2015/11936-2]CNPq [470853/2012-3]FCT doctoral grants [ SFRH/BD/105541/2014 ]FCT Investigator Programme [IF/00049/2012]info:eu-repo/semantics/publishedVersio

Chemical Structure and Localization of Levan, the Predominant Fructan Type in Underground Systems of Gomphrena marginata (Amaranthaceae)

Gomphrena marginata Seub. (Amaranthaceae) is an endemic species from Brazilian campos rupestres with a fructan accumulating underground reserve system. Analyses of high performance anion exchange chromatography (HPAEC–PAD) revealed the presence of the soluble carbohydrates glucose, fructose, sucrose, 1-kestose, 6-kestose, nystose and fructans with degree of polymerization (DP) up to approximately 40 fructose units. Data of 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy, including Heteronuclear Single-Quantum Correlation (HSQC) and Heteronuclear Multiple-Bonds Correlation (HMBC) showed the presence of β (2,6) linkages, characteristic of the linear molecule of levan-type fructan(2,6). These results confirmed previous studies suggesting that the reserve carbohydrate in the underground system of this species was levan-type fructans, similar to that of G. macrocephala. Structural analyses of the thickened underground system using light microscopy revealed a mixed origin system consisting mainly of a gemmiferous tuberous root with the upper region formed by short branched stems, both presenting vascular cylinders with unusual growth patterns. Fructan spherocrystals were visualized under polarized light and scanning electron microscopy (SEM) mostly in the cortex and vascular cylinder in both thickened stem and root. In addition to data reported in the literature concerning the occurrence of fructans in the Amaranthaceae, the results presented here suggest that fructans are a trait in this family while the levan-type fructan prevail in Gomphrena species

Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases

Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action

Combined fit to the spectrum and composition data measured by the Pierre Auger Observatory including magnetic horizon effects

The measurements by the Pierre Auger Observatory of the energy spectrum and mass composition of cosmic rays can be interpreted assuming the presence of two extragalactic source populations, one dominating the flux at energies above a few EeV and the other below. To fit the data ignoring magnetic field effects, the high-energy population needs to accelerate a mixture of nuclei with very hard spectra, at odds with the approximate E$^{-2}$ shape expected from diffusive shock acceleration. The presence of turbulent extragalactic magnetic fields in the region between the closest sources and the Earth can significantly modify the observed CR spectrum with respect to that emitted by the sources, reducing the flux of low-rigidity particles that reach the Earth. We here take into account this magnetic horizon effect in the combined fit of the spectrum and shower depth distributions, exploring the possibility that a spectrum for the high-energy population sources with a shape closer to E$^{-2}$ be able to explain the observations

Investigating the UHECR characteristics from cosmogenic neutrino limits with the measurements of the Pierre Auger Observatory

Cosmogenic neutrinos are expected to originate in the extragalactic propagation of ultra-high-energy cosmic rays (UHECRs), as a result of their interactions with background photons. Due to these reactions, the visible Universe in UHECRs is more limited than in neutrinos, which instead could reach us without interacting after traveling cosmological distances. In this contribution, we exploit a multimessenger approach by computing the expected energy spectrum and mass composition of UHECRs at Earth corresponding to combinations of spectral parameters and mass composition at their sources, as well as parameters related to the UHECR source distribution, and by determining, at the same time, the associated cosmogenic neutrino fluxes. By comparing the expected UHECR observables to the energy spectrum and mass composition measured at the Pierre Auger Observatory above 1017.8 eV and the expected neutrino fluxes to the most updated neutrino limits, we show the dependence of the neutrino fluxes on the characteristics of the the properties of the potential sources of UHECRs, such as their cosmological evolution and maximum redshift. In addition, the fraction of protons compatible with the data is also investigated in terms of expected neutrino fluxes