Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats.

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS: The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS: Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS: Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, ß-catenin and PCNA expression. SIGNIFICANCE: These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.

Schistosomicidal Activity of Alkyl-phenols from the Cashew Anacardium occidentale against Schistosoma mansoni Adult Worms.

Bioassay-guided study of the ethanol extract from the cashew Anacardium occidentale furnished cardol triene (1), cardol diene (2), anacardic acid triene (3), cardol monoene (4), anacardic acid diene (5), 2-methylcardol triene (6), and 2-methylcardol diene (7). 1D- and 2D-NMR experiments and HRMS analysis confirmed the structures of compounds 1-7. Compounds 2 and 7 were active against Schistosoma mansoni adult worms in vitro, with LC50 values of 32.2 and 14.5 µM and selectivity indices of 6.1 and 21.2, respectively. Scanning electron microscopy of the tegument of male worms in the presence of compound 7 at 25 µM after 24 h of incubation showed severe damage as well as peeling and reduction in the number of spine tubercles. Transmission electron microscopy analyses revealed swollen mitochondrial membrane, vacuoles, and altered tegument in worms incubated with compound 2 (25 µM after 24 h). Worms incubated with compound 7 (25 µM after 24 h) had lysed interstitial tissue, degenerated mitochondria, and drastically altered tegument. Together, the results indicated that compound 7 presents promising in vitro schistosomicidal activity.

Antischistosomal and Cytotoxic Effects of the Essential Oil of Tetradenia riparia (Lamiaceae).

This paper reports on the antischistosomal and cytotoxic effects of the essential oil obtained from Tetradenia riparia leaves (TR-EO). At concentrations of 50 and 100 µg/mL, TR-EO killed all the worms after 120 and 24 h of incubation, respectively. At a concentration equal to or higher than 50 µg/mL, this oil also separated the coupled pairs and decreased the adult worm motor activity after incubation periods higher than 72 h. In addition, at 120 h of incubation, TR-EO slightly decreased the number of eggs produced by Schistosoma mansoni adult worms and significantly reduced the percentage of developed eggs, in a dose-dependent manner. XTT-colorimetric assays showed that the tested TR-EO concentrations were not considerably cytotoxic to V79 cells (IC50 = 253.5 µg/mL). The effects of TR-EO on egg development were noteworthy; therefore, this essential oil deserves further investigation to identify the chemical constituents that elicit activity against S. mansoni.

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 µg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity.

Lipoxygenase inhibitory activity of Cuspidaria pulchra and isolated compounds.

This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-ß-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 µM respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic.