Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review

Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs

Cyperus articulatus L. (Cyperaceae) Rhizome Essential Oil Causes Cell Cycle Arrest in the G2/M Phase and Cell Death in HepG2 Cells and Inhibits the Development of Tumors in a Xenograft Model

Cyperus articulatus L. (Cyperaceae), popularly known in Brazil as “priprioca” or “piriprioca”, is a tropical and subtropical plant used in popular medical practices to treat many diseases, including cancer. In this study, C. articulatus rhizome essential oil (EO), collected from the Brazilian Amazon rainforest, was addressed in relation to its chemical composition, induction of cell death in vitro and inhibition of tumor development in vivo, using human hepatocellular carcinoma HepG2 cells as a cell model. EO was obtained by hydrodistillation using a Clevenger-type apparatus and characterized qualitatively and quantitatively by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detection (GC-FID), respectively. The cytotoxic activity of EO was examined against five cancer cell lines (HepG2, HCT116, MCF-7, HL-60 and B16-F10) and one non-cancerous one (MRC-5) using the Alamar blue assay. Cell cycle distribution and cell death were investigated using flow cytometry in HepG2 cells treated with EO after 24, 48 and 72 h of incubation. The cells were also stained with May–Grunwald–Giemsa to analyze the morphological changes. The anti-liver-cancer activity of EO in vivo was evaluated in C.B-17 severe combined immunodeficient (SCID) mice with HepG2 cell xenografts. The main representative substances of this EO sample were muskatone (11.6%), cyclocolorenone (10.3%), α-pinene (8.26%), pogostol (6.36%), α-copaene (4.83%) and caryophyllene oxide (4.82%). EO showed IC50 values for cancer cell lines ranging from 28.5 µg/mL for HepG2 to >50 µg/mL for HCT116, and an IC50 value for non-cancerous of 46.0 µg/mL (MRC-5), showing selectivity indices below 2-fold for all cancer cells tested. HepG2 cells treated with EO showed cell cycle arrest at G2/M along with internucleosomal DNA fragmentation. The morphological alterations included cell shrinkage and chromatin condensation. Treatment with EO also increased the percentage of apoptotic-like cells. The in vivo tumor mass inhibition rates of EO were 46.5–50.0%. The results obtained indicate the anti-liver-cancer potential of C. articulatus rhizome EO