Natural compounds have shown good potential for the discovery of new chemotherapeutics for the treatment of Chagas’ disease. Recently, our group reported the effective trypanocidal activity of (−)-elatol, extracted from the red macroalgae Laurencia dendroidea present in the Brazilian coast against Trypanosoma cruzi. However, the mechanism of action of this compound has remained unclear. There are only hypotheses concerning its action on mitochondrial function. Here, we further investigated the mechanisms of action of (−)-elatol on trypomastigotes of T. cruzi. For this, we evaluated some biochemical alterations in trypomastigotes treated with (−)-elatol. Our results show that (−)-elatol induced depolarization of the mitochondrial membrane, an increase in the formation of mitochondrial superoxide anion and loss of cell membrane and DNA integrity. Additionally, (−)-elatol induced formation of autophagic vacuoles and a decrease in cell volume. All together, these results suggest that the trypanocidal action of (−)-elatol involves multiple events and mitochondria might be the initial target organelle. Our hypothesis is that the mitochondrial dysfunction leads to an increase of ROS production through the electron transport chain, which affects cell membrane and DNA integrity leading to different types of parasite death.

Thermosensitive hydrogels based on chitosan/pectin (CS/Pec) and CS/Pec/gold nanoparticles (CS/Pec/AuNPs) were successfully prepared with different AuNP levels. Using a tilting method, gelation temperature was demonstrated to decrease when the amount of AuNPs increased and pectin concentrations decreased. The presence of AuNPs in the CS/Pec composite was evaluated via WAXS and UV-vis techniques, while SEM analysis assessed the average size of pores (350-600μm). All samples were extremely cytocompatible with many cell types, such as normal kidney epithelial cells (VERO cells), epithelial colorectal adenocarcinoma cells (HT-29 cells), HPV-16 positive human cervical tumour cells (SiHa cells), kidney epithelial cells (LLCMK cells) and murine macrophage cells (J774A1 cells). Cell viability assays using the MTT method upon mouse preosteoblastic cells (MC3T3-E1 cells) showed that CS/Pec and CS/Pec/AuNPs composites had the potential to foster proliferation and growth of bone cells, making them possible stimulators for reconstruction of bone tissues.

Hydrogels based on alginate and tanfloc (a cationic biopolymer obtained from natural condensed tannins) were successfully prepared. Tanfloc (TN) presents high aqueous solubility at pHs lower than 10; it contains substituted amino sites and molar weight of ca. 600,000gmol. A factorial design (2) was used to optimize the yield of alginate/tanfloc polyelectrolyte complexes (PECs). Dialysis recovered the overplus of alginate (AG) no complexed with TN. These materials were characterized by thermal analyses (TGA/DTG and DSC), zeta potential, and FTIR, while SEM technique depicted a rough surface on AG/TN complex, containing non-homogeneous pores. Indeed, the AG and TN were tailored to elicit scaffold materials with outstanding cytocompatibility, mainly upon mouse preosteoblastic cells because of reconstruction of bone tissues (119% at 10days). The AG/TN complex also displayed antioxidant and bactericidal activities against Staphylococcus aureus (S. aureus). Besides, the pristine TN fostered bacteriostatic and bactericidal performances towards S. aureus and Escherichia coli. However, for our best knowledge, no studies were still carried out on TN and TN-based materials for medical purpose.

Our group assays natural products that are less toxic and more effective than available nitroheterocycles as promising therapeutic options for patients with Chagas disease. Our previous study reported the trypanocidal activity of eupomatenoid-5, a neolignan isolated from the leaves of Piper regnellii var. pallescens, against the three main parasitic forms of Trypanosoma cruzi. The present study further characterizes the biochemical and morphological alterations induced by this compound to elucidate the mechanisms of action involved in the cell death of T. cruzi. We show that eupomatenoid-5 induced oxidative imbalance in the three parasitic forms, especially trypomastigotes, reflected by a decrease in the activity of trypanothione reductase and increase in the formation of reactive oxygen species (ROS). A reduction of mitochondrial membrane potential was then triggered, further impairing the cell redox system through the production of more ROS and reactive nitrogen species. Altogether, these effects led to oxidative stress, reflected by lipid peroxidation and DNA fragmentation. These alterations are key events in the induction of parasite death through various pathways, including apoptosis, necrosis, and autophagy.

Alzheimer’s disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aβ) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia , Limonium brasiliense , Paullinia cupana , Poincianella pluviosa , Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aβ 25–35 toxicity in SH-SY5Y cells. The effect of the EAF of S . adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 ( S . adstringens , P . pluviosa and L . brasiliense ) protected SH-SY5Y cells from Aβ 25-35 -induced toxicity. The EAF of S . adstringens at 15.62 μg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aβ 25-35 -induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S . adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aβ 25–35 , which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G . ulmifolia , L . brasiliense , P . cupana , P . pluviosa and S . adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.