Leishmaniasis is caused by protozoans of the genus Leishmania, and its treatment is highly toxic, leading to treatment discontinuation and the emergence of resistant strains. In this study, we assessed the leishmanicidal activity and chemical composition of red propolis collected from the Amazon-dominated region of northern Tocantins State, Brazil. The MTT assay was employed to determine the samples’ activity against Leishmania amazonensis promastigotes and their cytotoxicity against RAW macrophages. Spectrophotometric assays were utilised to measure the concentrations of total phenolics and flavonoids, while high-performance liquid chromatography coupled to a mass spectrometer (LC-MS/MS) was used to determine the chemical composition. An in silico study was conducted to evaluate which compounds from Brazilian Amazon red propolis may correlate with this biological activity. Brazilian Amazon red propolis exhibited a high concentration of phenolic compounds and an inhibitory activity against L. amazonensis, with an IC₅₀ ranging from 23.37 to 36.10 µg/mL. Moreover, fractionation of the propolis yielded a fraction with enhanced bioactivity (16.11 µg/mL). Interestingly, neither the propolis nor its most active fraction showed cytotoxicity towards macrophages at concentrations up to 200 µg/mL. The red colour and the presence of isoflavonoid components (isoflavones, isoflavans, and pterocarpans) confirm that the substance is Brazilian red propolis. However, the absence of polyprenylated benzophenones suggests that this is a new variety of Brazilian red propolis. The in silico study performed with two of the main leishmanicidal drug targets using all compounds identified in Amazon red propolis reported that liquiritigenin was the compound that exhibited the best electronic interaction parameters, which was confirmed in an assay with promastigotes using a standard. The findings indicate that Amazon red propolis possesses leishmanicidal activity, low toxicity, and significant biotechnological potential.

Vernonanthura brasiliana (L.) H. Rob is a medicinal plant used for the treatment of several infections. This study aimed to evaluate the antileishmanial activity of V. brasiliana leaves using in vitro and in silico approaches. The chemical composition of V. brasiliana leaf extract was determined through liquid chromatography-mass spectrometry (LC-MS). The inhibitory activity against Leishmania amazonensis promastigote was evaluated by the MTT method. In silico analysis was performed using Lanosterol 14alpha-demethylase (CYP51) as the target. The toxicity analysis was performed in RAW 264.7 cells and Tenebrio molitor larvae. LC-MS revealed the presence of 14 compounds in V. brasiliana crude extract, including flavonoids, flavones, sesquiterpene lactones, and quinic acids. Eriodictol (ΔGbind = −9.0), luteolin (ΔGbind = −8.7), and apigenin (ΔGbind = −8.6) obtained greater strength of molecular interaction with lanosterol demethylase in the molecular docking study. The hexane fraction of V. brasiliana showed the best leishmanicidal activity against L. amazonensis in vitro (IC₅₀ 12.44 ± 0.875 µg·mL⁻¹) and low cytotoxicity in RAW 264.7 cells (CC₅₀ 314.89 µg·mL⁻¹, SI = 25.30) and T. molitor larvae. However, the hexane fraction and Amphotericin-B had antagonistic interaction (FICI index ≥ 4.0). This study revealed that V. brasiliana and its metabolites are potential sources of lead compounds for drugs for leishmaniasis treatment.

Infectious and Parasitic Diseases (IPD) remain a challenge for medicine due to several interconnected reasons, such as antimicrobial resistance (AMR). American tegumentary leishmaniasis (ATL) is an overlooked IPD causing persistent skin ulcers that are challenging to heal, resulting in disfiguring scars. Moreover, it has the potential to extend from the skin to the mucous membranes of the nose, mouth, and throat in both humans and various animals. Given the limited effectiveness and AMR of current drugs, the exploration of new substances has emerged as a promising alternative for ATL treatment. Arrabidaea brachypoda (DC). Bureau is a native Brazilian plant rich in dimeric flavonoids, including Brachydin (BRA), which displays antimicrobial activity, but still little has been explored regarding the development of therapeutic formulations. In this work, we present the design of a low-cost liquid formulation based on the use of Pluronic F127 for encapsulation of high BRA concentration (LF-B500). The characterization techniques revealed that BRA-loaded F127 micelles are well-stabilized in an unusual worm-like form. The in vitro cytotoxicity assay demonstrated that LF-B500 was non-toxic to macrophages but efficient in the inactivation of forms of Leishmania amazonensis promastigotes with IC₅₀ of 16.06 µg/mL. The results demonstrated that LF-B500 opened a new perspective on the use of liquid formulation-based natural products for ATL treatment.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The aim was to chemically characterize the essential oil (EO) obtained from P. brevipedunculata (EO-PB) by hydrodistillation and a microemulsion formulated with EO (ME-PB), Tween 80 and Transcutol P, assess the leishmanicidal effect against Leishmania (L.) amazonensis promastigotes and cytotoxicity against RAW 264.7. EO-PB and ME-PB were analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Monoterpene hydrocarbons were noteworthy among the identified compounds. The main EO-PB constituents were α-pinene and limonene, followed by neral and geranial, which were maintained in ME-PB. EO-PB presented an inhibitory concentration (IC₅₀) of 20 µg/mL and ME-PB of 0.93 µg/mL. ME-PB inhibition towards the parasite was 20-fold higher than that of EO-PB. This indicated that EO incorporation to the microemulsion resulted in optimized biological activity. Selectivity indices indicate that ME-PB is more selective concerning parasite inhibition. Thus, ME-PB may comprise an adequate approach against Leishmania, as the inhibitory concentration (IC₅₀) promastigotes was lower than that considered toxic for cells cell cytotoxicity of 50% (CC₅₀).

Background/Objectives: Leishmaniasis, caused by protozoa of the genus Leishmania, is a major global health issue due to the limitations of current treatments, which include low efficacy, high costs, and severe side effects. This study aimed to develop a more effective and less toxic therapy by utilizing zein nanoparticles (ZNPs) in combination with a nonpolar fraction (DCMF) from Fridericia platyphylla (Syn. Arrabidaea brachypoda), a plant rich in dimeric flavonoids called brachydins. Methods: Zein nanoparticles were used as carriers to encapsulate DCMF. The system was characterized by measuring particle diameter, polydispersity index, zeta potential, and encapsulation efficiency. Analytical techniques such as FTIR, DSC, and AFM were employed to confirm the encapsulation and stability of DCMF. Antileishmanial activity was assessed against Leishmania amazonensis promastigotes and amastigotes, while cytotoxicity was tested on RAW264.7 macrophages. Results: The ZNP-DCMF system exhibited favorable properties, including a particle diameter of 141 nm, a polydispersity index below 0.2, and a zeta potential of 11.3 mV. DCMF was encapsulated with an efficiency of 94.6% and remained stable for 49 days. In antileishmanial assays, ZNP-DCMF inhibited the viability of promastigotes with an IC50 of 36.33 μg/mL and amastigotes with an IC50 of 0.72 μg/mL, demonstrating higher selectivity (SI = 694.44) compared to DCMF alone (SI = 43.11). ZNP-DCMF was non-cytotoxic to RAW264.7 macrophages, with a CC50 > 500 μg/mL. Conclusions: Combining F. platyphylla DCMF with zein nanoparticles as a carrier presents a promising approach for leishmaniasis treatment, offering improved efficacy, reduced toxicity, and protection of bioactive compounds from degradation.