Malaria is an infectious disease and a serious public health problem in the world, with 3.3 billion people in endemic areas in 100 countries and about 200 million new cases each year, resulting in almost 1 million deaths in 2018. Although studies look for strategies to eradicate malaria, it is necessary to know more about its pathophysiology to understand the underlying mechanisms involved, particularly the redox balance, to guarantee success in combating this disease. In this review, we addressed the involvement of oxidative stress in malaria and the potential benefits of antioxidant supplementation as an adjuvant antimalarial therapy.

Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC₅₀ of 0.23 and 0.15 μg/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski’s rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity.

The treatment of leishmaniasis has limitations due to drug toxicity and the increasing resistance of the parasite. In this study, we analyze the role of oxidative stress in the pathogenesis and treatment of leishmaniasis, as well as in new therapeutic alternatives of natural origin. The evasion mechanisms against the host immune response involve surface molecules present in the parasite, which modulate oxidative stress to ensure its survival. Drug treatment requires strict monitoring to minimize adverse reactions and ensure patient safety, as mechanisms such as lipid peroxidation, mitochondrial dysfunction, and depletion of antioxidant defenses are associated with drug toxicity. Plant-derived products with antileishmanial activity impact the parasite’s redox balance, inducing apoptosis and reducing its parasitic load. Most studies are still in preliminary stages, making in vivo assays and clinical studies essential, along with the development of accessible formulations. Oxidative stress is involved in the pathogenesis of leishmaniasis, as Leishmania manipulates the host’s redox balance to survive. It also contributes to drug toxicity, as antimonials and amphotericin B increase reactive oxygen species, causing cellular damage. Several plant-derived compounds have demonstrated antileishmanial activity by modulating oxidative stress and promoting parasite apoptosis. Examples include alkaloids from Aspidosperma nitidum, lignans from Virola surinamensis, flavonoids from Geissospermum vellosii, and triterpenoids such as β-sitosterol. Although these compounds show promising selectivity, most studies remain in preliminary stages, requiring in vivo assays and clinical studies to confirm efficacy and safety, as well as the development of affordable formulations.

• Ethanol extract of Eleutherine plicata showed low in vitro and in vivo cytotoxic potential. • The dichloromethane fraction was cytotoxic to HepG2 and caused DNA. However, no toxicity was observed in vivo. • Isoeleutherin caused DNA damage by the comet method and activated caspase-8 in the in silico study.

From Eleutherine plicata, naphthoquinones, isoeleutherine, and eleutherol were isolated, and previous studies have reported the antioxidant activity of these metabolites. The present work evaluated the role of oxidative changes in mice infected with Plasmodium berghei and treated with E. plicata extract, fraction, and isolated compounds, as well as to verify possible oxidative changes induced by these treatments. E. plicata extracts were prepared from powder from the bulbs, which were submitted to maceration with ethanol, yielding the extract (EEEp), which was fractionated under reflux, and the dichloromethane fraction (FDMEp) was submitted for further fractionation, leading to the isolation of isoeleutherine, eleutherine, and eleutherol. The antimalarial activity was examined using the suppressive test, evaluating the following parameters of oxidative stress: trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH). Furthermore, the molecular docking of naphthoquinones, eleutherol, eleutherine, and isoeleutherine interactions with antioxidant defense enzymes was investigated, which was favorable for the formation of the receptor–ligand complex, according to the re-rank score values. Eleutherine and isoeleutherine are the ones with the lowest binding energy for catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx1), showing themselves as possible targets of these molecules in the involvement of redox balance. Data from the present study showed that treatments with E. plicata stimulated an increase in antioxidant capacity and a reduction in oxidative stress in mice infected with P. berghei, with naphthoquinones being responsible for reducing oxidative changes and disease severity.