Exploring Synthetic Dihydrobenzofuran and Benzofuran Neolignans as Antiprotozoal Agents against Trypanosoma cruzi.

Chagas disease is a neglected tropical disease that affects more than 8 million people. Although there are therapies against this disease, the search for new drugs is important because the current treatments show limited effectiveness and high toxicity. In this work, eighteen dihydrobenzofuran-type neolignans (DBNs) and two benzofuran-type neolignans (BNs) were synthesized and evaluated against amastigote forms of two Trypanosoma cruzi strains. The in vitro cytotoxicity and hemolytic activity of the most active compounds were also evaluated and their relationships with T. cruzi tubulin DBNs were investigated by an in silico approach. Four DBNs demonstrated activity against the T. cruzi Tulahuen lac-Z strain (IC50 from 7.96 to 21.12 µM), and DBN 1 exhibited the highest activity against the amastigote forms of the T. cruzi Y strain (IC50 3.26 µM). Compounds 1-4 showed CC50 values higher than antitrypanosomal activities, except for DBN 3. All DBNs with antitrypanosomal activity demonstrated CH50 higher than 100 µM. The in silico results indicated that DBNs 1, 2, and 4 are capable of destabilizing the dynamics of the tubulin-microtubule from the vinca site. These compounds displayed promising in vitro activity against T. cruzi, especially compound 1, and can be considered molecular prototypes for the development of new antiparasitic drugs.

The coasting time affects the quality of cumulus-oocyte complexes in superstimulated ewes.

We hypothesized that the coasting time may be beneficial to the quality of cumulus-oocyte complexes recovered from live ewes, as reported in cattle. The present study assessed the effect of coasting times on the quantity and quality of cumulus-oocyte complexes (COCs) in sheep. All ewes were subjected to the "Day 0 protocol", followed by an ovarian stimulation (80 mg of pFSH in three decreasing doses), varying only the coasting time [12 (G12), 36 (G36), or 60 h (G60]. In Experiment 1, data regarding follicular population was assessed. In Experiment 2, the COC quality was checked by their morphology, brilliant cresyl blue (BCB) test, evaluation of chromatin condensation pattern, and oocyte diameter. In Experiment 3, genes related to oocyte developmental competence were evaluated in BCB + COCs. The oocytes in the G60 group had more (P < 0.05) large follicles than the other groups and oocytes with a greater diameter than the G12. Oocyte morphology was similar (P > 0.05) among groups, as well as the BCB + COCs quantity. The G60-oocytes presented a better (P < 0.05) configuration of chromatin condensation compared with the other groups and a greater (P < 0.05) gene expression of BMP15, MATER, ZAR1, and PTGS2 compared with G12, and PTGS2 and HAS2 compared with G36 group. In conclusion, 60 h of coasting time positively affects the quality of COCs recovered after subjecting ewes to the "Day 0 protocol" and ovarian superstimulation. Implementing the appropriate coasting time to a given protocol can positively impact the in vitro embryo production outcomes in sheep.

Antibacterial, Antiparasitic, and Cytotoxic Activities of Chemical Characterized Essential Oil of Chrysopogon zizanioides Roots.

This study aimed to investigate the chemical composition as well as the antibacterial, antiparasitic, and cytotoxic potentialities of the Brazilian Chrysopogon zizanioides root essential oil (CZ-EO) In addition, CZ-EO cytotoxicity to LLCMK2 adherent epithelial cells was assessed. The major compounds identified in CZ-EO were khusimol (30.0 ± 0.3%), ß-eudesmol (10.8 ± 0.3%), α-muurolene (6.0 ± 0.1%), and patchouli alcohol (5.6 ± 0.2%). CZ-EO displayed optimal antibacterial activity against Prevotella nigrescens, Fusobacterium nucleatum, Prevotella melaninogenica, and Aggregatibacter actinomycetemcomitans, with Minimum Inhibitory Concentration (MIC) values between 22 and 62.5 µg/mL and Minimum Bactericidal Concentration (MBC) values between 22 and 400 µg/mL. CZ-EO was highly active against the L. amazonensis promastigote and amastigote forms (IC50 = 7.20 and 16.21 µg/mL, respectively) and the T. cruzi trypomastigote form (IC50 = 11.2 µg/mL). Moreover, CZ-EO showed moderate cytotoxicity to LLCMK2 cells, with CC50 = 565.4 µg/mL. These results revealed an interesting in vitro selectivity of CZ-EO toward the L. amazonensis promastigote and amastigote forms (Selectivity Index, SI = 78.5 and 34.8, respectively) and the T. cruzi trypomastigote form (SI = 50.5) compared to LLCMK2 cells. These results showed the promising potential of CZ-EO for developing new antimicrobial, antileishmanial, and antitrypanosomal drugs.

Anticariogenic Activity of Three Essential Oils from Brazilian Piperaceae.

The current trend toward using natural food additives, cosmetics, and medicines has motivated industries to substitute synthetic compounds for natural products. Essential oils (EOs) from medicinal plants are a well-known source of chemical compounds that display several interesting biological activities, including antimicrobial action. In this study, we investigated the antibacterial activity of EOs extracted from three Piperaceae species collected in the Brazilian Amazon region against a representative panel of cariogenic bacteria. The minimum inhibitory concentration (MIC) of the essential oils extracted from Peperomia pellucida (PP-EO), Piper marginatum (PM-EO), and Piper callosum (PC-EO) was determined against Streptococcus mutans, S. mitis, S. sanguinis, S. salivarius, S. sobrinus, Enterococcus faecalis, and Lactobacillus casei by using the microplate microdilution method. PM-EO, PC-EO, and PP-EO displayed antibacterial activity against all the tested cariogenic bacteria. PM-EO displayed the best inhibitory activity, with MIC values ranging from 50 to 500 µg/mL. The lowest MIC values were obtained for PM-EO against S. mitis (MIC = 75 µg/mL), Lactobacillus casei (MIC = 50 µg/mL), and S. mutans (MIC = 50 µg/mL). Gas chromatography mass spectrometry (GC-MS) analysis allowed the chemical composition of all the EOs to be identified. The main constituents of PM-EO, PC-EO, and PP-EO were 3,4-(methylenedioxy)propiophenone, α-pinene, and dillapiole, respectively. Finally, the compounds that were exclusively detected in PM-EO are highlighted. Our results suggest that PM-EO may be used in products for treating dental caries and periodontal diseases.

Antibacterial Activity of Essential Oils against Oral Pathogens.

This updated review article covers the literature between 2011 and 2021 on the antibacterial activity of EOs against the main bacteria that cause caries and periodontal diseases. The criteria to classify the in vitro antibacterial activity of EOs is updated and the most promising results are addressed.

Antischistosomal Activity of Essential Oils: An Updated Review.

This review article covers literature on the antischistosomal activity of essential oils (EOs) between 2011 and 2021. Criteria for classifying results from in vitro schistosomicidal assays are proposed for the first time. Parameters to evaluate the in vitro antischistosomal potential of EOs other than their ability to cause the death of Schistosoma mansoni adult worms (e. g., couple separation, egg laying, and egg development inhibition) are also addressed and discussed.

5-Fluorouracil induces inflammation and oxidative stress in the major salivary glands affecting salivary flow and saliva composition.

This study aimed to elucidate the effect of 5-fluorouracil (5-FU) on the histological aspects of the major salivary glands, salivary flow and saliva composition using an established oral mucositis model in hamsters. Oral mucositis was induced by two intraperitoneal administrations of 5-FU in two consecutive days (60 and 40mg/kg), followed by cheek pouch mucosa scratch, on day 4. The Pilocarpine-stimulated salivary flow was measured 4 and 10days after the first 5-FU injection. Salivary glands were harvested for histopathological analysis, measurement of inflammatory cells, quantification of pro-inflammatory cytokines (TNF-α and IL-1ß), investigation of cell death and cell proliferation. Oxidative stress and oxidative defense system were also investigated in the salivary gland tissues using MDA (malondialdehyde), nitrite, non-protein sulfhydryl groups (NP-SH), SOD (superoxide dismutase) and CAT (catalase). In addition, the CAT and lysozyme activities and the IgA and SOD levels were evaluated in the saliva samples. 5-FU significantly reduced the pilocarpine-stimulated salivary flow rate on the 4th experimental day, associated with an increase in the SOD levels in saliva. Recovery of the salivary flow and SOD were observed on day 10, when an increase in the saliva lysozyme levels was detected. In addition, 5-FU promoted vacuolization in parotid (P) and periductal edema in submandibular (SM) gland, combined with an increase in the inflammatory cells influx, mostly observed on the 4th day in SM gland and on 4th and 10th days in P. Oxidative stress was found mostly on day 10 in SM, SL and P glands, associated with release of proinflammatory cytokines, observed in SM and SL glands, but not in P. 5-FU induces an inflammatory response in the major salivary glands, most observed ten days after its first injection, which may contribute to the major salivary glands hypofunction, leading to alterations in the salivary flow rate and composition.