We have previously described the anti-allergic activities of a pooled fraction of tetranortriterpenoids (TNTPs) containing 6α-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin and methyl angolensate isolated from the seeds of Carapa guianensis. In the present study, we performed in vitro studies in order to elucidate the mechanisms by which TNTPs present their anti-allergic effects and to identify the bioactive compound(s) present in such fraction. Here, we show that in vitro incubation of eosinophils with the pooled TNTP fraction, as well as with each one of the five isolated tetranortriterpenoids, impaired the adhesion of eosinophils to tumor necrosis factor-α (TNF-α)-primed tEND.1 endothelial cells. Furthermore, the individual or pooled TNTPs impaired CCL11/eotaxin-mediated chemotaxis. By contrast, pooled TNTPs failed to inhibit adhesion and chemotaxis of T lymphocytes. However, TNTPs were able to impair anti-CD3 monoclonal antibody-induced T cell proliferation and the expression of CD25 and CD69. These data suggest that TNTPs prevent T cell activation. Pretreatment of splenocytes with the pooled TNTP fraction, as well as with each one of the five isolated TNTPs, inhibited ovalbumin (OVA)-induced in vitro production of interleukin-2, chemokine (C-C motif) ligand 11 (CCL11) and regulated on activation normal T cell expressed and secreted (RANTES, also known as CCL5). TNTPs (except 6α-acetoxygedunin) also impaired nuclear factor-κB (NFκB) nuclear translocation in OVA-challenged splenocytes. Taken together, these results demonstrate that the anti-allergic effects of TNTPs isolated from C. guianensis might rely on their ability to inhibit eosinophil migration, as well as the activation of T lymphocytes, which is shared by the five isolated TNTPs.
Family Clusiaceae is spread throughout tropical as well as temperate zones, presenting many triterpenes, reported as selective antitumoral agents. The aim of this study is to isolate and identify triterpenes from Clusia studartiana C. M. Vieira & Gomes da Silva and evaluate their cytotoxicity in melanoma (SKMEL 28) and myeloid leukemia (K562) cell lines. Thus, the hexanic extract was processed by phytochemical methods to isolate and purify the pentacyclic triterpenes: 3-oxo-friedelin (1), 3-βhydroxy-friedelin (2) and 3-oxo-olean-12-en-28-oic-acid (3), identified by spectroscopic methods. Cytotoxicity was evaluated by MTT assay, apoptosis/necrosis by Annexin V/PI, caspase activity by FLICA in flow cytometry and P-gp modulation was measured by interference in the efflux of Rhodamine 123. From the results, triterpenes 2 and 3 showed inhibitory effect in K562 cells proliferation, and only the compound 3 was able to increase percentage of AnnexinV + PI in cells (p<0.05), with 40% increase in caspase 3/7 + cells and showed inhibition on P-gp activity.
A identificação de funcionalidades ocultas pela análise do binário de um software embarcado é uma tarefa desafiadora. Este desafio se deve ao fato da própria complexidade em se analisar um binário. É de particular interesse da área da segurança da informação garantir a inexistência de tais funcionalidades uma vez que elas podem comprometer o comportamento de um software. Este trabalho propõe um método para localizar trechos de código suspeitos por meio de uma depuração supervisionada do software embarcado, auxiliada pela análise estática dos grafos de fluxo de controle e de chamadas.
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