Anti-inflammatory effects and possible mechanism of action of lupeol acetate isolated from Himatanthus drasticus (Mart.) Plumel

<p>Abstract</p> <p>Background</p> <p>The species <it>Himatanthus drasticus </it>is popularly known in Northeast Brazil as "janaguba" and belongs to the family Apocynaceae. The latex collected from its stem bark is used for several purposes including anti-inflammatory properties and presents among its bioactive constituents the pentacyclic triterpene lupeol. The objective of the present work was to study <it>in vivo </it>and <it>in vitro </it>the lupeol acetate (LA) isolated from the plant latex, in several models of inflammation.</p> <p>Methods</p> <p>Male Swiss mice (25-30 g, 6-24 animals per group) were administered with LA, 30 min before the test initiation. In the evaluation of analgesic activity the formalin test was used. The anti-inflammatory activity was evaluated by the following tests: paw edema induced by carrageenan and dextran, and the carrageenan-induced neutrophil migration into peritoneal cavities. Furthermore, the effect of LA on the myeloperoxidase release (MPO, an inflammation biomarker) from human neutrophils was also determined, as well as its antioxidant potential by the DPPH assay.</p> <p>Results</p> <p>In the formalin test, LA (10, 25 and 50 mg/kg, i.p.) inhibited both the 1^st(neurogenic, 0-5 min) and mainly the 2^nd(inflammatory, 20-25 min) phase. Naloxone completely reversed the LA effect, indicating the participation of the opioid system. LA also significantly inhibited carrageenan- and dextran-induced paw edemas, as well as the neutrophil migration to the peritoneal cavity evaluated by the carrageenan-induced pleurisia. In this model, the effect of a very low dose of LA (0.1 mg/kg) was potentiated by the same dose of pentoxifylline (PTX), a known TNF-alpha inhibitor. LA (25 and 50 μg/ml) was also very effective in inhibiting MPO released from stimulated human neutrophils, and significantly decreased the number of cells expressing iNOS activity in the paw of mice submitted to carrageenan-induced edema, suggesting a drug involvement with the NO system.</p> <p>Conclusions</p> <p>The anti-inflammatory effect of LA probably involves the opioid system, as indicated by the complete blockade of the opioid antagonist naloxone. Furthermore, the LA effect was potentiated by PTX (a TNF-alpha inhibitor). LA also decreased the number of iNOS cells, suggesting the participation of pro-inflammatory cytokines and the NO system in the drug action.</p

Modulation of the Antibiotic Activity by Extracts from Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan

The aim of this study was to verify the possible interactions between ethanol extracts of Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan, combined with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli isolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC). The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract of Anadenanthera macrocarpa against EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 μg/mL. Among the β-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin against S. aureus 358

Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC