Anti-Leishmania amazonensis Activity, Cytotoxic Features, and Chemical Profile of Allium sativum (Garlic) Essential Oil.

Human tegumentary leishmaniasis (HTL) is a serious tropical disease caused by Leishmania amazonensis. Developing new leishmanicidal agents can help overcome current treatment challenges, such as drug resistance and toxicity. Essential oils are a source of lipophilic substances with diverse therapeutic properties. This study aimed to determine the anti-L. amazonensis activity, cytotoxicity, and chemical profile of Allium sativum essential oil (ASEO). The effect of ASEO on parasite and mammalian cells viability was evaluated using resazurin and MTT assays, respectively. The oil's effect against intracellular amastigotes was also determined. Transmission electron microscopy was used to assess the ultrastructural changes induced by ASEO. In addition, the chemical constituents of ASEO were identified by gas chromatography-mass spectrometry (GC-MS). The cytotoxic potential was evaluated in vitro and in silico. The oil displayed IC50 of 1.76, 3.46, and 3.77 µg/mL against promastigotes, axenic, and intracellular amastigotes, respectively. Photomicrographs of treated parasites showed plasma membrane disruption, increased lipid bodies, and autophagic-like structures. ASEO chemical profiling revealed 1,2,4,6-tetrathiepane (24.84%) and diallyl disulfide (16.75%) as major components. Computational pharmacokinetics and toxicological analysis of ASEO's major components demonstrated good oral bioavailability and better toxicological endpoints than the reference drugs. Altogether, the results suggest that ASEO could be an alternative drug candidate against HTL.

Delving into the Mechanisms of Sponge-Associated Enterobacter against Staphylococcal Biofilms.

Staphylococci are one of the most common causes of biofilm-related infections. Such infections are hard to treat with conventional antimicrobials, which often lead to bacterial resistance, thus being associated with higher mortality rates while imposing a heavy economic burden on the healthcare system. Investigating antibiofilm strategies is an area of interest in the fight against biofilm-associated infections. Previously, a cell-free supernatant from marine-sponge-associated Enterobacter sp. inhibited staphylococcal biofilm formation and dissociated the mature biofilm. This study aimed to identify the chemical components responsible for the antibiofilm activity of Enterobacter sp. Scanning electron microscopy confirmed that the aqueous extract at the concentration of 32 µg/mL could dissociate the mature biofilm. Liquid chromatography coupled with high-resolution mass spectrometry revealed seven potential compounds in the aqueous extract, including alkaloids, macrolides, steroids, and triterpenes. This study also suggests a possible mode of action on staphylococcal biofilms and supports the potential of sponge-derived Enterobacter as a source of antibiofilm compounds.

Antileishmanial Screening, Cytotoxicity, and Chemical Composition of Essential Oils: A Special Focus on Piper callosum Essential Oil.

Leishmania amazonensis is the etiological agent of tegumentary leishmaniasis, a disease characterized by the emergence of cutaneous and mucocutaneous ulcerated lesions that can evolve into severe destruction of skin tissue. Treatment of the disease is often accompanied by high toxicity and variable efficacy. Essential oils stand out for having diverse pharmacological properties. Here, we screened a panel of fourteen essential oils for their anti-L. amazonensis activity, cytotoxicity, and chemical profile. Lippia sidoides (LSEO) and Piper callosum (PCEO) oils displayed the best anti-promastigote and anti-amastigote activities with IC50 of 31 and 21 µg/ml, respectively. PCEO was the safest oil with a desirable selectivity index >10. In addition, PCEO showed no cytotoxicity against the VERO line and erythrocytes. PCEO-treated amastigotes displayed mitochondrial membrane depolarization and high levels of intracellular ROS. Safrole (54.72 %) was the main component of PCEO. The results described here highlight the use of essential oils to combat tegumentary leishmaniasis.

Chemical composition and anti-Mayaro virus activity of Schinus terebinthifolius fruits.

Brazilian traditional medicine has explored the antiviral properties of many plant extracts, including those from the Brazilian pepper tree, Schinus terebinthifolius. In the present study, we investigated the chemical composition and anti-mayaro virus (MAYV) activity of S. terebinthifolius fruit. Extensive virucidal activity (more than 95%) was detected for the ethyl acetate extract and the isolated biflavonoids. From the ethyl acetate extract of Schinus terebinthifolius fruits, two bioflavonoids were isolated ((2S, 2″S)-2,3,2″,3″-tetrahydroamentoflavone and agathisflavone), which showed strong virucidal activity against Mayaro virus. Furthermore, several other compounds like terpenes and phenolics were identified by hyphenated techniques (GC-MS, LC-MS and HPLC-UV), as well as by mass spectrometry. Immunofluorescence assay confirmed antiviral activity and transmission electron microscopy revealed damage in viral particles treated with biflavonoids. The data suggest the direct action of the extract and the biflavonoids on the virus particles. The biflavonoids tetrahydroamentoflavone and agathisflavone had strong virucidal activity and reduced MAYV infection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00698-z.

Ethyl Acetate Fraction and Isolated Phenolics Derivatives from Mandevilla moricandiana Identified by UHPLC-DAD-ESI-MSn with Pharmacological Potential for the Improvement of Obesity-Induced Endothelial Dysfunction.

Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg/mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction.

Umbelliferone esters with antibacterial activity produced by lipase-mediated biocatalytic pathway.

OBJECTIVE: The present report describes the enzymatic acylation of umbelliferone with different vinyl esters as acyl donors biocatalyzed by the commercial lipase Novozym® 435, and the investigation for their antibacterial activity against ATCC and clinical strains isolated from hospital infection sites. RESULTS: The umbelliferone esters (1-5) were synthesized through the acylation reaction of 7-hydroxy-2H-chromen-2-one with different long chain vinyl esters catalyzed by the lipase Novozym 435. The reaction conditions were: 10% Novozym 435; tetrahydrofuran:acetone (3:1) for the reactions with acetate, propionate and butyrate vinyl esters 50-90% conversion, and (9:1) for decanoate and laurate vinyl esters 10-15% conversion; acyl donor/umbelliferone molar ratio of 10:1 and 60 °C. All the umbelliferone esters were characterized NMR and (HRMS). The antibacterial activity of the products were tested using the broth microdilution method in order to determine the minimum inhibitory concentration (MIC). The results displayed by 7-laurate and 7-decanoate-umbelliferone esters showed the highest antibacterial potential, with 1 mM inhibitory activity for ATCC 33591, a methicillin and oxacillin resistant Staphylococcus aureus strain. They were also able to inhibit gram-negative bacterial strains, such as Pseudomonas aeruginosa (MIC 0.5 mM) and Klebsiella pneumoniae (MIC 1 mM). In addition, 7-laurate- and 7-decanoate-umbelliferone esters were able to inhibit all clinical strains (MIC 1 mM; except 7-laurate-umbelliferone in which MIC 0.5 mM against 55a). CONCLUSIONS: This is the first study performing the biocatalysis of umbelliferone followed by the purification of the products and the antibacterial evaluation.

Piper capitarianum essential oil: a promising insecticidal agent for the management of Aedes aegypti and Aedes albopictus.

Mosquitoes are responsible for serious public health problems worldwide, and as such, Aedes aegypti and Aedes albopictus are important vectors in the transmission of dengue, chikungunya, and Zika in Brazil and other countries of the world. Due to growing resistance to chemical insecticides among populations of vectors, environmentally friendly strategies for vector management are receiving ever more attention. Essential oils (EOs) extracted from plants have activities against insects with multiple mechanisms of action. These mechanisms hinder the development of resistance, and have the advantages of being less toxicity and biodegradable. Thus, the present study aimed to evaluate the chemical composition of the EOs obtained from Piper capitarianum Yunck, as well as evaluating their insecticidal potential against Aedes aegypti and A. albopictus, and their toxicity in relation to Artemia salina. The yields of the EOs extracted from the leaves, stems, and inflorescences of P. capitarianum were 1.2%, 0.9%, and 0.6%, respectively, and their main constituents were trans-caryophyllene (20.0%), α-humulene (10.2%), ß-myrcene (10.5%), α-selinene (7.2%), and linalool (6.0%). The EO from the inflorescences was the most active against A. aegypti and A. albopictus, and exhibited the respective larvicidal (LC50 = 87.6 µg/mL and 76.1 µg/mL) and adulticide activities (LC50 = 126.2 µg/mL and 124.5 µg/mL). This EO was also the most active in the inhibition of AChE, since it presented an IC50 value of 14.2 µg/mL. Its larvicidal effect was observed under optical and scanning electron microscopy. Additionally, non-toxic effects against A. salina were observed. Docking modeling of trans-caryophyllene and α-humulene on sterol carrier protein-2 (SCP-2) suggests that both molecules have affinity with the active site of the enzyme, which indicates a possible mechanism of action. Therefore, the essential oil of P. capitarianum may be used in the development of new insecticide targets for the control of A. aegypti and A. albopictus in the Amazonian environment.

Herbal Medicinal Products from Passiflora for Anxiety: An Unexploited Potential.

Herbal medicines containing Passiflora species have been widely used to treat anxiety since ancient times. The species Passiflora incarnata L. is included in many Pharmacopoeias, and it is the most used species in food, cosmetic, and pharmaceutical industries. However, there are around 600 species of the genus Passiflora and probably other species that can be used safely. Thus, this article was based on a search into the uses of the main species of the genus Passiflora with anxiolytic activity and its main secondary metabolites and some pharmacological studies, patents, and registered products containing Passiflora. Furthermore, the Brazilian Regulatory Health Agency Datavisa, Medicines and Healthcare Products Regulatory Agency of the United Kingdom, and the European Medicines Agency websites were consulted. The results showed that Passiflora species have health benefits but clinical trials are still scarce. The complexity of Passiflora extracts creates challenges for the development of herbal medicines. P. incarnata is the most studied species of the genus and the most used in natural anxiolytic herbal medicine formulations. However, there are hundreds of Passiflora species potentially useful for medicinal and nutraceutical purposes that are still little explored.

Evaluation of the chemical composition and antioxidant activity of extracts and fractions of Ocotea notata (Ness) Mez (Lauraceae).

The specie Ocotea notata (Nees & Mart). Mez is a tree with 5 meters high, that can be found in restinga regions in the Brazilian coast. This study describes a phytochemical investigation, total phenolic content and the antioxidant activity of extracts and fractions by DPPH and ORAC. Phenolic content revealed equivalent concentration between evaluated samples, similar to found in the leave extract (66.4 mEq GA/g). By DPPH, extracts and fractions showed effective concentration (EC50) lower than the standards Ginkgo biloba 761® (23.60 ± 0.64 µg/ml) and quercetin (6.06 ± 0, 92 µg/mL); for the ORAC method, ethyl acetate partition showed a value of 2.06 mmol Trolox equivalent g-1 better than obtained in Ginkgo biloba (1.03 ± 0.25 mmol.Trolox equivalent g-1. The butanol partition (0.52 mmol.Trolox equivalent g-1) and the aqueous residue (0.74 mmol Trolox equivalent g-1) have a lesser ORAC potential than ethyl acetate partition. The butanolic partition, investigated by LC-DAD-MS/MS and QTOF-MS, revealed six major compounds: miquelianin (1), isoquercitrin (2), quercitrin (3), kaempferol-3-O-pentose (4), afzelin (5) and isorhamnetin-glucuronide (6).

Phenolic compounds from Tocoyena bullata mart (Rubiaceae) with inhibitory activity in mast cells degranulation.

Glycosylated flavonoids, caffeoylquinic acid and 3,5-dicaffeoylquinic acid have been identified in the ethyl acetate partition from the crude ethanol extract of Tocoyena bullata (Rubiaceae) leaves. The fraction containing the mixture of flavonol rutin and a tetraglycosylated flavonoid showed 89.2% inhibition and the mixture of isoquercitrin and 3,5-dicaffeoylquinic acid showed 88.5% inhibition of mast cell degranulation. These results demonstrated that the tetraglycosylated flavonoid, rutin, isoquercitrin and 3,5-dicaffeioylquinic acid were the most promising phenolics for inhibition of mast cell degranulation. For the first time the identification of phenolic constituents and their correlation with inhibitory effect on mast cell degranulation were reported in this work.

β-Carboline-1-propionic acid alkaloid: antileishmanial and cytotoxic effects

ABSTRACT Pentavalent antimonials and amphotericin B remain as the main drugs to treat human leishmaniasis. However, the high toxicity and variable efficacy of treatment have stimulated the search for novel drug candidates. Naturally occurring alkaloids have a long history of antileishmanial activity. Here, we investigate the effects of the β-carboline-1-propionic acid alkaloid isolated from Quassia amara L., Simaroubaceae, against Leishmania amazonensis and Leishmania infatum. The alkaloid was isolated after liquid-liquid fractionation followed by chromatographic purification of the Q. amara methanol extract. The antileishmanial activity was evaluated by the microdilution method, using resazurin as the viability indicator. In addition, annexin and propidium iodide were used to detect parasites undergoing apoptosis. The anti-amastigote activity of the β-carboline-1-propionic acid alkaloid was determined by the infection of RAW 264.7 macrophages. The alkaloid displayed leishmanicidal activity against Leishmania amazonensis and L. infantum promastigotes and intracellular amastigotes with 50% inhibitory concentration ranging from 2.7 ± 0.82 to 9.4 ± 0.5 µg/ml and selectivity indexes >10. Moreover, apoptotic Leishmania amazonensis (19.5%) and L. infantum (40.4%) promastigotes were detected after 5 h incubation with the alkaloid. Finally, the β-carboline-1-propionic acid alkaloid inhibited the production of NO of infected macrophages, suggesting that the intracellular amastigote elimination occurs in a nitrosative stress-independent way. The results shown here suggest that the β-carboline-1-propionic acid alkaloid has potential as an antileishmanial agent.

PLGA nanoparticles optimized by Box-Behnken for efficient encapsulation of therapeutic Cymbopogon citratus essential oil.

This study aimed to optimize Cymbopogon citratus essential oil loaded into PLGA-nanoparticles by investigating the effect of processing variables (sonication time, ultrasound power, and essential oil/polymer ratio) on encapsulation efficiency and particle mean hydrodynamic diameter using Box-Behnken design. Nanoparticles were prepared by an emulsification/solvent diffusion method and physicochemically characterized by FTIR, DSC and TGA/DTA. Cytotoxicity was evaluated in human HaCat keratinocytes by WST-1 and LDH assays. The optimized formulation had a hydrodynamic mean diameter of 277 nm, a polydispersity index of 0.18, a Zeta potential of -16 mV and an encapsulation efficiency of 73%. Nanoparticle characterization showed that only citral was incorporated in nanocarriers, with some amount adsorbed on their surface, and highlighted the potential in increasing the oil thermal stability. The drug release profile demonstrated a biphasic pattern with a substantial sustained release depending on diffusion from the polymeric matrix. Toxicity effects on cell viability of pure essential oil at low concentrations were significantly eliminated when encapsulated. Results revealed the ability of PLGA-nanoparticles to improve essential oil physicochemical characteristics, by controlling release and reducing toxicity, suggesting their potential use in pharmaceutical preparations.

Brazilian stingless bee propolis and geopropolis: promising sources of biologically active compounds

ABSTRACT Stingless bee products such as honey, pollen, propolis, and geopropolis have been used for centuries in traditional medicine for the treatment of several illnesses. Investigation of the biological activity of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties. About 20% of total Neotropical stingless bees can be found in Brazil. Despite the species diversity, studies on their biological activity are scarce. The present review focuses on the antioxidant and antimicrobial activities of propolis and geopropolis from Brazilian stingless bees. In addition, the toxicity of these natural products was addressed. In order to provide new evidences for the toxic potential of propolis and geopropolis components, an in silico analysis was performed using the ADMET PredictorTM software. We observed that most of studies evaluated only crude ethanol extracts of a limited number of stingless bees species. Propolis and geopropolis displayed antioxidant capacity and antimicrobial activity. Concerning the toxic potential, the extracts of stingless bees propolis and geopropolis were considered safe. Nonetheless, in vitro and in vivo toxicological studies are still necessary.

Rutin derivatives obtained by transesterification reactions catalyzed by Novozym 435: Antioxidant properties and absence of toxicity in mammalian cells.

Flavonoids are one of the most important and diversified phenolic groups among products of natural origin. An important property of this metabolite class is the antioxidant action. This study evaluated the antioxidant and cytotoxic activities and oxidative stress of transesterification products of the flavonoid rutin, catalyzed by Novozym® 435. The presence of monoacetate and diacetate was confirmed by quantitative evaluation of the retention times (rutin, 15.68 min; rutin monoacetate, 18.14 min; and rutin diacetate, 18.57 min) and by the data from LC-MS and NMR 1H and 13C. The experiment showed excellent conversion values of 96% in total acetates (rutin monoacetate and diacetate). These results confirmed that rutin derivatives have antioxidant potential, as evaluated by the ORAC method (rutin standard: 0.53 ± 0.08 µM Trolox/g and rutin derivatives: 2.33 ± 1.08 µM Trolox/g) and also show low cytotoxicity in human and animal cells. Rutin derivatives reduced the production of reactive oxygen species in RAW macrophages as well. Many qualities attributed to rutin derivatives make them promising potential candidates for use as nutraceuticals, including their high amounts of antioxidants, biological potential and low toxicity, which contribute to the reduction of oxidative stress.

In vitro release and anti-herpetic activity of Cymbopogon citratus volatile oil-loaded nanogel

Abstract This study aimed to prepare hydrogel containing Cymbopogon citratus (DC.) Stapf, Poaceae, volatile oil encapsulated in poly (d,l-lactide-co-glycolide) nanoparticles and to evaluate its in vitro anti-herpetic activity. Polymeric nanoparticles were prepared by solvent emulsification-diffusion method and incorporated in carbomer hydrogels. In vitro release profiles for the nanogel, loaded nanoparticles and hydrogel containing free oil were evaluated by dialysis. Inhibitory activities against Herpes simplex for the formulations were investigated in Vero cells. Hydrogel was developed using nanoparticles with mean diameter of 217.1 nm and negative Zeta potential (−20.5 mV). Volatile oil release profile showed a biphasic pattern with an initial faster release and subsequent sustained phase in all formulations. Nanogel strongly inhibited virus in a non-cytotoxic concentration, 42.16 times lower than free oil, 8.76 and 2.23 times than loaded nanoparticles and hydrogel containing free oil, respectively. These results highlight the potential of nanogel to protect oil against volatilization, control release and improve its anti-herpetic activity.

Development of Nanoemulsions to Enhance the Antileishmanial Activity of Copaifera paupera Oleoresins.

Based on the ethnopharmacological evidences about the antileishmanial activity of Copaifera spp. oleoresins, the effects of crude extracts and fractions of oleoresin of two specimens from Copaifera paupera were evaluated on Leishmania amazonensis and Leishmania infantum strains. The oleoresin rich in α-copaene (38.8%) exhibited the best activity against L. amazonensis (IC50 = 62.5 µg/mL) and against L. infantum (IC50 = 65.9 µg/mL). The sesquiterpene α-copaene isolated was tested alone and exhibited high antileishmanial activity in vitro with IC50 values for L. amazonensis and L. infantum of 17.2 and 11.4 µg/mL, respectively. In order to increase antileishmanial activity, nanoemulsions containing copaiba oleoresin and α-copaene were developed and assayed against L. amazonensis and L. infantum promastigotes. The nanoemulsion containing α-copaene (NANOCOPAEN) showed the best activity against both species, with IC50 of 2.5 and 2.2 µg/mL, respectively. This is the first report about the antileishmanial activity of α-copaene.

Alpinia Essential Oils and Their Major Components against Rhodnius nasutus, a Vector of Chagas Disease.

Species of the genus Alpinia are widely used by the population and have many described biological activities, including activity against insects. In this paper, we describe the bioactivity of the essential oil of two species of Alpinia genus, A. zerumbet and A. vittata, against Rhodnius nasutus, a vector of Chagas disease. The essential oils of these two species were obtained by hydrodistillation and analyzed by GC-MS. The main constituent of A. zerumbet essential oil (OLALPZER) was terpinen-4-ol, which represented 19.7% of the total components identified. In the essential oil of A. vittata (OLALPVIT) the monoterpene ß-pinene (35.3%) was the main constituent. The essential oils and their main constituents were topically applied on R. nasutus fifth-instar nymphs. In the first 10 min of application, OLALPVIT and OLALPZER at 125 µg/mL provoked 73.3% and 83.3% of mortality, respectively. Terpinen-4-ol at 25 µg/mL and ß-pinene at 44 µg/mL provoked 100% of mortality. The monitoring of resistant insects showed that both essential oils exhibited antifeedant activity. These results suggest the potential use of A. zerumbet and A. vittata essential oils and their major constituents to control R. nasutus population.

Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts.

CONTEXT: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity. OBJECTIVE: This study evaluated the anti-L. amazonensis activity of Citrus sinensis (L.) Osbeck (Rutaceae) extracts. MATERIALS AND METHODS: Citrus sinensis dried leaves were subjected to maceration with hexane (CH), ethyl acetate (CEA), dichloromethane/ethanol (CD/Et - 1:1) or ethanol/water (CEt/W - 7:3). Leishmania amazonensis promastigotes were treated with C. sinensis extracts (1-525 µg/mL) for 120 h at 27 °C. Ultrastructure alterations of treated parasites were evaluated by transmission electron microscopy. Cytotoxicity of the extracts was assessed on RAW 264.7 and J774.G8 macrophages after 48-h treatment at 37 °C using the tetrazolium assay. In addition, Leishmania-infected macrophages were treated with CH and CD/Et (10-80 µg/mL). RESULTS: CH, CD/Et and CEA displayed antileishmanial activity with 50% inhibitory activity (IC50) of 25.91 ± 4.87, 54.23 ± 3.78 and 62.74 ± 5.04 µg/mL, respectively. Parasites treated with CD/Et (131.2 µg/mL) presented severe alterations including mitochondrial swelling, lipid body formation and intense cytoplasmic vacuolization. CH and CD/Et demonstrated cytotoxic effects similar to that of amphotericin B in the anti-amastigote assays (SI of 2.16, 1.98 and 1.35, respectively). Triterpene amyrins were the main substances in CH and CD/Et extracts. In addition, 80 µg/mL of CD/Et reduced the number of intracellular amastigotes and the percentage of infected macrophages in 63% and 36%, respectively. CONCLUSION: The results presented here highlight C. sinensis as a promising source of antileishmanial agents.

Evaluation of Antiplasmodial activity of extracts and constituents from Ampelozizyphus amazonicus.

BACKGROUND: Ampelozizyphus amazonicus Ducke, a plant that is widely used by the population of the Amazonian region to prevent and treat malaria, was investigated in this work, which describes, for the first time, the antiplasmodial activity of its extracts and associates this activity with its isolated constituents. METHODS: Different extracts with solvents of increasing polarity (hexane, chloroform, ethanol, and water) were obtained of the root bark. This procedure resulted in extracts that were characterized for their constituents. The cytotoxicity and activity of the extracts against Plasmodium berghei (schizontocidal activity, liver stage) and Plasmodium falciparum (3D7 and Dd2 strains, erythrocyte stage) were assessed in vitro. RESULTS: Of the four extracts assayed against P. berghei, the chloroform extract showed the greatest activity, with an inhibitory concentration 50% (IC50) value of 30.1 µg/mL, followed by the aqueous extract (IC50 = 39.9 µg/mL). The chloroform extract exhibited the highest antiplasmodial activity in the erythrocyte stage of P. falciparum, with an IC50 value lower than 15 µg/mL. Fractionation of this more active extract led to the isolation and elucidation of pentacyclic triterpenes, lupeol, betulin and betulinic acid, which showed antiplasmodial activities with IC50 values ranging from 5.6 to 80.30 µM. The most active of these, betulinic acid, was further quantified in the extracts by high-performance liquid chromatography-photodiode array detector analyzes. The higher amount was found in the chloroform extract, which was the most active one against P. falciparum. CONCLUSION: The results obtained in this work may partly explain the popular intake of A. amazonicusas an antimalarial remedy in the Amazon region.

Natural Products: Insights into Leishmaniasis Inflammatory Response.

Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease.