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Chagas disease (CHD) is the highest economic burden parasitosis worldwide and the most important cardiac infection, without therapeutic alternatives to halt or reverse its progression. In CHD-experimental models, antioxidant and anti-inflammatory compounds have demonstrated therapeutic potential in cardiac dysfunction. Theobroma cacao polyphenols are potent natural antioxidants with cardioprotective and anti-inflammatory action, which are susceptible to degradation, requiring technological approaches to guarantee their protection, stability, and controlled release. Here, 21 cocoa polyphenol-rich microencapsulates were produced by spray-drying and freeze-drying techniques using two wall materials (maltodextrin and gum arabic). Chemical (total and individual phenolic content and antioxidant activity), structural (morphology), and biological parameters (cytotoxicity, trypanocidal, antioxidant, and immunomodulatory activities) were assessed to determine the most efficient microencapsulation conditions on Trypanosoma cruzi-infected myocardioblast and macrophage cells. Significant antiproliferative properties against infected cells (superior to benznidazole) were found in two microencapsulates which also exhibited cardioprotective properties against oxidative stress, inflammation, and cell death.

Acute myelogenous leukemia (AML) is one of the most lethal cancers, lacking a definitive curative therapy due to essential constraints related to the toxicity and efficacy of conventional treatments. This study explores the co-adjuvant potential of Lippia alba essential oils (EO) for enhancing the effectiveness and selectivity of two chemotherapy agents (cytarabine and clofarabine) against AML cells. EO derived from L. alba citral chemotype were produced using optimized and standardized environmental and extraction protocols. Rational fractionation techniques were employed to yield bioactive terpene-enriched fractions, guided by relative chemical composition and cytotoxic analysis. Pharmacological interactions were established between these fractions and cytarabine and clofarabine. The study comprehensively evaluated the cytotoxic, genotoxic, oxidative stress, and cell death phenotypes induced by therapies across AML (DA-3ER/GM/EVI1+) cells. The fraction rich in citral (F2) exhibited synergistic pharmacological interactions with the studied chemotherapies, intensifying their selective cytotoxic, genotoxic, and pro-oxidant effects. This shift favored transitioning from necrosis to a programmed cell death phenotype (apoptotic). The F2-clofarabine combination demonstrated remarkable synergistic anti-leukemic performance while preserving cell integrity in healthy cells. The observed selective antiproliferative effects may be attributed to the potential dual prooxidant/antioxidant behavior of citral in L. alba EO.

Se implementaron metodologías de análisis por electroforesis capilar (CE) y cromatografía líquida de alta eficiencia (HPLC) para la separación y cuantificación de (±)-catequina, (-)-epicatequina, (-)-epigalocatequina, galato de (-)-epicatequina y galato de (-)-epigalocatequina, en 5 muestras de 3 variedades de cacao cultivadas en Colombia. La técnica de HPLC fue más reproducible que la CE, que, sin embargo, resultó ser más rápida, económica y menos contaminante. Se cuantificaron, por HPLC y CE (estándar externo), (±)-catequina (0,07-0,79 mg/g de cacao) y (-)-epicatequina (1,99-9,66 mg/g de cacao) en los extractos acuosos de las tres variedades de cacao.

Abstract B. palustris Heering (Asteraceae), has been previously characterized as having an unusual essential oil composition with C9-/C10-polyacetylenes as main components, and mono- and sesqui-terpenes/terpenoids at minor or trace levels. In this work, new insights into the chemical composition of this oil are presented: 1. TLC profiles using different visualization reagents for their characterization, 2. chemical analyses combining HRGC/qMS, HRGC/HRMS-TOF and HRGCxHRGC/HRMS-TOF, and 3. radical scavenging activity assay using the DPPH methodology were performed. The best TLC visualization conditions for the polyacetylenic components of the oil were obtaining using UVλ= 365 nm and vanillin/H3PO4, while the original application of NaDi (1-naphtol + N,N-dimethyl-p-phenylendiamine) demonstrated to be the best option to visualize the lachnophyllum acid methyl esters fraction. Gas chromatography/mass spectrometry protocols allowed the detection of 63 components in B. palustris oil: 39 of them were identified, 6 tentatively assigned without LRI information, and 18 could not be identified. Most of the identified components were mono- and sesquiterpenes and their derivatives. Ten of them are informed for the first time in B. palustris oil [α-pinene epoxide, rosefuran, epi-cubebol, cubebol, germacrene D-4-ol, junenol, epi-α-cadinol, epi-α-muurolol, germacra-4(15),5,10(14)-trien-1-β-ol and oplopanone]. C9-/C10-polyacetylenes (baccharisdyine/lachnophyllum acid derivatives) were confirmed as the main components of the oil, while other polyacetylenes were tentatively identified and their possible structures are discussed. The deconvolution analyses on HRGCxHRGC/HRMS-TOF allowed the identification of a lachnophyllum lactone isomer (undefined stereochemistry), co-eluting with the (cis)-lachnophyllum acid methyl ester peak. Finally, B. palustris oil was found to be an inactive DPPH radical scavenger.

Abstract Searching for new bioactive molecules to design insecticides is a complex process since pesticides should be highly selective, active against the vector, and bio-safe for humans. Aiming to find natural compounds for mosquito control, we evaluated the insecticidal activity of essential oils (EOs) from 20 American native plants against Aedes aegypti larvae using bioassay, biochemical, and in silico analyses. The highest larvicide activity was exhibited by EOs from Steiractinia aspera (LC50 = 42.4 µg/mL), Turnera diffusa (LC50 = 70.9 µg/mL), Piper aduncum (LC50 = 55.8 µg/mL), Lippia origanoides (chemotype thymol/carvacrol) (LC50 = 61.9 µg/mL), L. origanoides (chemotype carvacrol/thymol) (LC50 = 59.8 µg/mL), Hyptis dilatata (LC50 = 61.1 µg/mL), Elaphandra quinquenervis (LC50 = 61.1 µg/mL), and Calycolpus moritzianus (LC50 = 73.29 µg/mL) after 24 h. This biological activity may be related to the disruption of the electron transport chain through the mitochondrial protein complexes. We hypothesized that the observed EOs' effect is due to their major components, where computational approaches such as homology modeling and molecular docking may suggest the possible binding pose of secondary metabolites that inhibit the mitochondrial enzymes and acetylcholinesterase activity (AChE). Our results provided insights into the possible mechanism of action of EOs and their major compounds for new insecticide designs targeting the mitochondria and AChE activity in A. aegypti for effective and safe insecticide.

according to the World Health Organization, 20-30% of people in the world have diseases and disorders of the musculoskeletal system, which are accompanied by: scootiness, discomfort, reduced walking amplitude and painful sensations. With scientific progress there are new perspectives, but there is another side of negative factors associated with a small-duty way of life and lack of manual activity. During the day: sitting at the table, in front of the computer, with the phone hand, violating the rule of “student position” by being in an uncomfortable position for more than 1 – 2 hours. These factors contribute to gipotonichy muscles and lead to the formation of imbalances of the spinal musculature, eventually develop degenerative-dystrophic diseases of the musculoskeletal apparatus. Analysis of skinning of early diagnostics of changes and deformations of the posture in adolescence. The problematics of the XXI century themes is not new. Analyzing scientific articles on the topic of postural disorders, one should pay attention to the fact that the main efforts are aimed at improving health and preventing diseases. This will ensure the proper level of health and reduce the incidence of diseases in the population. Objective description. This publication analyzes the results of preventive and diagnostic examinations, carried out by preadolescent patients with postural disorders in the sagittal and frontal planes. Materials and methods. The results of prophylactic and diagnostic review were analyzed, in the city of Kiev, the Communal non-profit organization "Consultative and Diagnostic Center" of the Svyatoshinsky district, Phil 2, from May to July 2022. Participated 490 children of preadolescent age, 11 - 15 years, with impaired position in the sagittal and frontal areas. With consent of parents or guardians. The following examination methods were used: visual diagnostics, somatoscopy, manual and musculoskeletal testing, functional tests to determine the stages of positional disorders, X-ray and magnetic resonance imaging. For convenience, the documentation is formed, and the patient card is developed. The majority of the patients with impaired posture in the sagittal and frontal planes are treated by conservative methods. Conclusions. The main purpose of the preventive-diagnostic examination is to detect skeletal and muscular imbalances at the initial stage, to choose active procedures, to follow recommendations for elimination of negative body movements during the day. The child's health depends on the constant monitoring of parents and consultations of doctors. There should be cooperation of physicians, parents and children, observance of simple rules and prophylactic measures.

Obesity is characterized by an expansion of adipose tissue due to excessive accumulation of triglycerides in adipocytes, causing hypertrophy and hyperplasia, followed by hypoxia, alterations in adipocyte functionality, and chronic inflammation. However, current treatments require changes in lifestyle that are difficult to achieve and some treatments do not generate sustained weight loss over time. Therefore, we evaluated the effect of the essential oil (EO) of Lippia alba (Verbenaceae) carvone chemotype on viability, lipid mobilization, and adipogenesis of adipocytes in two normal and pathological cellular models in vitro. In 3T3-L1 adipocytes, a normal and a pathological model of obesity were induced, and then the cells were treated with L. alba carvone chemotype EO to evaluate cell viability, lipid mobilization, and adipogenesis. L. alba carvone chemotype EO does not decrease adipocyte viability at concentrations of 0.1, 1, and 5 µg/mL; furthermore, there was evidence of changes in lipid mobilization and adipogenesis, leading to a reversal of adipocyte hypertrophy. These results could be due to effects produced by EO on lipogenic and lipolytic pathways, as well as modifications in the expression of adipogenesis genes. L. alba carvone chemotype EO could be considered as a possible treatment for obesity, using the adipocyte as a therapeutic target.

Abstract Stickiness of vegetative tissues has evolved multiple times in different plant families but is rare and understudied in flowers. While stickiness in general is thought to function primarily as a defense against herbivores, it may compromise mutualistic interactions (such as those with pollinators) in reproductive tissues. Here, we test the hypothesis that stickiness on flower petals of the High-Andean plant, Bejaria resinosa (Ericaceae), functions as a defense against florivores. We address ecological consequences and discuss potential trade-offs associated with a repellant trait expressed in flowers that mediate mutualistic interactions. In surveys and manipulative experiments, we assess florivory and resulting fitness effects on plants with sticky and non-sticky flowers in different native populations of B. resinosa in Colombia. In addition, we analyze the volatile and non-volatile components in sticky and non-sticky flower morphs to understand the chemical information context within which stickiness is expressed. We demonstrate that fruit set is strongly affected by floral stickiness but also varies with population. While identifying floral stickiness as a major defensive function, our data also suggest that the context-dependency of chemical defense functionality likely arises from differential availability of primary pollinators and potential trade-offs between chemical defense with different modes of action.

Highlights Most secondary metabolites tentatively identified in H. brasiletto are homoisoflavones. Hidroalcoholic extract of H. brasiletto protects C. elegans from Cd toxicity The extract diminished Cd-induced damage to reproduction, growth, and locomotion. Cd-induced oxidative stress and translocation of DAF-16 are blocked by the extract.

Some of the challenges to developing greener sample preparation procedures are related to finding solvents and practices with low environmental impacts. Given the importance of CO2, water, and ethanol compared to other green solvents in flavonoid extractions, it is convenient to explore changes in how they are employed. Depending on temperature and pressure, these three solvents may present total or partial miscibility that can be used conveniently in sample preparation. In this work, the Lippia origanoides (Verbenaceae family) vegetal material remnant after essential oil distillation was extracted with either aqueous ethanol (EtOH), ethanol-modified supercritical CO2 (EtOHCO2), or two coexisting CO2 fluid phases [(CO2)2]. The latter was the extractive practice that afforded higher selectivity and yield of pinocembrin (Pn) and galangin (Gn), two important active ingredients for pharmaceutical applications. EtOH extraction was the practice with the highest whole yield, and its extract contained mainly glycosylated compounds, in contrast to those extraction systems that involved CO2. The presence of CO2 allowed selective extraction of nonglycosylated flavonoids, possibly due to π−π intermolecular interactions with them. Flavonoids whose B-ring is a benzene or phenol group were recovered in higher amount. By means of the EtOHCO2 and (CO2)2 techniques, the extraction/isolation of Pn and Gn was achieved with less ethanol consumption and lower environmental impacts. The best setup was extraction with (CO2)2 and isolation by preparative HPLC. These results are promising for increasing selectivity and yield in some specific sample preparations.

Hyptis colombiana (Lamiaceae family), a species also treated as Cantinoa colombiana in a recently segregated genus from Hyptis, is a perennial herb or subshrub native to the Andes of northern South America. H. colombiana leaves are commonly used in traditional medicine to treat respiratory and digestive illnesses. In this study, H. colombiana plants at different phenological stages (vegetative, flowering, and post-flowering) were harvested to obtain essential oils (EOs) and extracts (from fresh plant materials or post-distillation waste) whose chemical compositions and antioxidant activities were determined. H. colombiana EOs distilled by microwave-assisted hydrodistillation were analyzed by GC/MS/FID, and hydroalcoholic extracts obtained from fresh plant materials or post-distillation waste were analyzed by UHPLC-ESI+/−-Orbitrap-MS. The antioxidant activity was evaluated by the ABTS+• and ORAC assays. The principal compounds found in EOs were sesquiterpene hydrocarbons (65%); specifically, (E)-β-caryophyllene and germacrene D. Pyranone, rosmarinic acid, rutin, and p-hydroxybenzoic acid were the main constituents in H. colombiana extracts. After analyzing the chemical composition and antioxidant activity (ORAC) of EOs and hydroethanolic extracts from flowering H. colombiana plants, minimal variations were found. It is advisable to harvest H. colombiana plants during their flowering stage to acquire EOs and extracts that can be utilized in the agro-industry of EOs and their natural derivatives.

The work studied the methanogenic microbial consortium in a coal mine from the Bogotá basin in Colombia. Ex situ coal-enrichment cultures were established for in vitro growth and de novo gas production. Biogenic gas produced by cultures was analyzed by gas chromatography using thermal conductivity and flame ionization detectors. Cultures were used to isolate microbial specimens and to generate 16S rRNA gene libraries employing bacterial and archaeal primer sets. The gas chromatographic analysis showed methane production at 37 oC, but not at 60 oC, where CO2 was the major component of the biogenic gas. 16S rRNA gene sequence analysis of microbial isolates and clone libraries established that the methanogenic microbial consortium was formed by bacteria species from Bacillus and Gracilibacter genera plus archaea from the Methanothermobacter genus. This methanogenic microbial consortium was potentially responsible for biogenic gas generation in La Ciscuda coal mine. The results suggested that these methanogens produced methane by hydrogenotrophic or CO2 reduction pathways.

The insertion of circular economy principles into the essential oil (EO) production chain aims to reduce waste generation and make integral use of harvested plant material. Higher profits from integral use with reduced waste generation contribute to the eventual use of the EO value chain as an alternative to illicit crops in Colombia (mostly coca). In this study, Java-type citronella (Cymbopogon winterianus) and palmarosa (C. martinii) plant materials were used in two consecutive processes to obtain EOs and extracts. The residual biomass after EO distillation was subjected to ultrasound-assisted hydroethanolic extraction to afford extracts that contained bioactive compounds. Citronella and palmarosa were distilled with typical EO yields (1.0 ± 0.1% for citronella; 0.41 ± 0.06% for palmarosa; n = 5) either through hydrodistillation assisted by microwave radiation or through steam distillation, and their composition (determined via GC/FID/MS analysis) and physicochemical parameters fell within their ISO standard specifications. The concentration of citronellal, the major compound of citronella oil, was 500 ± 152 mg/g. Geraniol, the main component of palmarosa oil, was found at 900 ± 55 mg/g. The citronella and palmarosa hydroalcoholic extracts (4–11% yield) were analyzed with UHPLC-ESI-Orbitrap-MS, which permitted the identification of 30 compounds, mainly C-glycosylated flavones and hydroxycinnamic acids. Both extracts had similar antioxidant activity values, evaluated using the ABTS+● and ORAC assays (110 ± 44 µmol Trolox®/g extract and 1300 ± 141 µmol Trolox®/g extract, respectively).

The species Zanthoxylum caribaeum belongs to the Rutaceae family, from which several chemical nuclei are known, including alkaloids and coumarins. In addition, its essential oil has been characterized, showing differences in composition and various antimicrobial activities. In the present study, the essential oil of Z. caribaeum collected in the department of Tolima, central Colombia, was characterized by gas chromatography with mass selective detector (GC-MS). The essential oil showed a composition of about 43 compounds (including major and minor), whose main components, according to their abundance, are the following: germacrene D (228.0 ± 1.6 mg/g EO), (E)-β-farnesene (128.0 ± 1.5 mg/g EO), β-elemene (116.0 ± 1.6 mg/g EO) and (E)-nerolidol (74.0 ± 2.2 mg/g EO). This oil was tested against microorganisms that affect cocoa production in Colombia and in tropical countries where the production of this commodity is very important for the economy. The antifungal tests were performed on the fungal species Moniliophthora roreri and showed promising and significant activity, inhibiting growth by more than 95% at concentrations of 50 µL/mL and 100 µL/mL. This remarkable antifungal activity could be due to the presence of major and minor compounds that synergistically enhance the activity.

Sloanea is a plant genus, native to tropical regions, used in medicinal practices for its anti-inflammatory properties. This study aimed to determine the antioxidant activity, sun protective factor (SPF), and antifungal of extracts obtained from two species of Sloanea and to develop extract-based gels with antioxidants, photoprotective, and anti-Candida albicans effects. Ethanolic extracts from S. medusula and S. calva collected in Chocó, Colombia, were used for antioxidant activity and SPF determination using the DPPH assay and the Mansur equation, respectively. Extracts were characterized using HPLC-MS and used to prepare the gels. The viscosity of the extract-based gels was evaluated using an MCR92 rheometer. In addition, the anti-Candida activity of extracts against five yeasts and anti-C. albicans of gels were evaluated following the Clinical and Laboratory Standards Institute M27, 4th Edition. High DPPH radical scavenging activity (42.4% and 44.7%) and a high SPF value (32.5 and 35.4) were obtained for the extracts of S. medusula and S. calva, respectively. Similarly, extract-based gels showed significant DPPH radical scavenging activity of 54.5% and 53.0% and maximum SPF values of 60 and 57. Extract from S. medusula showed an important antifungal activity against C. albicans (minimal inhibitory concentration (MIC) of 2 µg/mL). In contrast, S. calva extract was active against C. krusei, C. albicans (MIC of 2 µg/mL) and C. tropicalis (MIC of 4 µg/mL). Sloanea medusula gel (0.15%) exhibited an important C. albicans growth inhibition (98%), while with S. calva gel (0.3%) growth inhibition was slightly lower (76%). Polyphenolic and triterpenoid compounds were tentatively identified for S. medusula and S. calva, respectively. Both extracts can be considered promising sources for developing photoprotective gels to treat skin infections caused by C. albicans.

Abstract Background Parasite persistence, exacerbated and sustained immune response, and continuous oxidative stress have been described to contribute to the development of the cardiac manifestations in Chronic Chagas Disease. Nevertheless, there are no efficient therapies to resolve the Trypanosoma cruzi infection and prevent the disease progression. Interestingly, trypanocide, antioxidant, and immunodulatory properties have been reported separately for some major terpenes, as citral (neral plus geranial), limonene, and caryophyllene oxide, presents in essential oils (EO) extracted from two chemotypes (Citral and Carvone) of Lippia alba. The aim of this study was to obtain L. alba essential oil fractions enriched with the aforementioned bioactive terpenes and to evaluate the impact of these therapies on trypanocide, oxidative stress, mitochondrial bioenergetics, genotoxicity, and inflammatory markers on T. cruzi-infected macrophages. Methods T. cruzi-infected J774A.1 macrophage were treated with limonene-enriched (ACT1) and citral/caryophyllene oxide-enriched (ACT2) essential oils fractions derived from Carvone and Citral-L. alba chemotypes, respectively. Results ACT1 (IC50 = 45 ± 1.7 μg/mL) and ACT2 (IC50 = 80 ± 1.9 μg/mL) exhibit similar trypanocidal effects to Benznidazole (BZN) (IC50 = 48 ± 2.5 μg/mL), against amastigotes. Synergistic antiparasitic activity was observed when ACT1 was combined with BZN (∑FIC = 0.52 ± 0.13 μg/mL) or ACT2 (∑FIC = 0.46 ± 1.7 μg/mL). ACT1 also decreased the oxidative stress, mitochondrial metabolism, and genotoxicity of the therapies. The ACT1 + ACT2 and ACT1 + BZN experimental treatments reduced the pro-inflammatory cytokines (IFN-γ, IL-2, and TNF-α) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Conclusion Due to its highly trypanocidal and immunomodulatory properties, ACT1 (whether alone or in combination with BZN or ACT2) represents a promising L. alba essential oil fraction for further studies in drug development towards the Chagas disease control.

Apical periodontitis (AP) develops as a result of an immune response to pulpal bacterial infection, and various cytokines are involved in the pathogenesis of AP, with Interleukin (IL)-1 being considered a key cytokine. The role of IL-1 in the pathogenesis of AP has been well studied. It is known that IL-1 expression in periapical lesions correlates closely with the development of AP. IL-1 is a potent bone-resorptive cytokine that induces osteoclast formation and activation. Hence, inhibiting its signaling with IL-1 receptor antagonist (IL-1RA) results in a reduction in periapical lesion size. On the other hand, IL-1 is also a central cytokine that combats bacterial infection by activating innate immune responses. Therefore, a complete loss of IL-1 signaling leads to a failure to limit bacterial dissemination and consequently exacerbates AP. In vivo, IL-1 expression is tightly regulated and its signaling is modulated to optimize the immune response. Obesity causes systemic low-grade chronic inflammation and increases the risk of cardiovascular, renal, and other disorders. In experimentally induced AP, obesity significantly increases periapical bone loss, albeit the underlying mechanism remains unclear. Recent technological innovations have enabled more comprehensive and detailed analyses than previously, leading to new insights into the role of IL-1RA in regulating IL-1 signaling, and modulating apical lesion progression in obesity. In this review, we provide a brief overview of the function of IL-1 in AP development, with special emphasis on the latest findings in normal weight and obese states.

Salvia aratocensis (Lamiaceae) is an endemic shrub from the Chicamocha River Canyon in Santander (Colombia). Its essential oil (EO) was distilled from the aerial parts of the plant via steam distillation and microwave-assisted hydrodistillation and analyzed using GC/MS and GC/FID. Hydroethanolic extracts were isolated from dry plants before distillation and from the residual plant material after distillation. The extracts were characterized via UHPLC-ESI(+/−)-Orbitrap-HRMS. The S. aratocensis essential oil was rich in oxygenated sesquiterpenes (60–69%) and presented τ-cadinol (44–48%) and 1,10-di-epi-cubenol (21–24%) as its major components. The in vitro antioxidant activity of the EOs, measured via an ABTS+• assay, was 32–49 μmol Trolox® g−1 and that measured using the ORAC assay was 1520–1610 μmol Trolox® g−1. Ursolic acid (28.9–39.8 mg g−1) and luteolin-7-O-glucuronide (1.16–25.3 mg g−1) were the major S. aratocensis extract constituents. The antioxidant activity of the S. aratocensis extract, obtained from undistilled plant material, was higher (82 ± 4 μmol Trolox® g−1, ABTS+•; 1300 ± 14 μmol Trolox® g−1, ORAC) than that of the extracts obtained from the residual plant material (51–73 μmol Trolox® g−1, ABTS+•; 752–1205 μmol Trolox® g−1, ORAC). S. aratocensis EO and extract had higher ORAC antioxidant capacity than the reference substances butyl hydroxy toluene (98 μmol Trolox® g−1) and α-tocopherol (450 μmol Trolox® g−1). S. aratocensis EOs and extracts have the potential to be used as natural antioxidants for cosmetics and pharmaceutical products.

The large-scale use of alcohol (OH)-based disinfectants to control pathogenic viruses is of great concern because of their side effects on humans and harmful impact on the environment. There is an urgent need to develop safe and environmentally friendly disinfectants. Essential oils (EOs) are generally recognized as safe (GRAS) by the FDA, and many exhibit strong antiviral efficacy against pathogenic human enveloped viruses. The present study investigated the virucidal disinfectant activity of solutions containing EO and OH against DENV-2 and CHIKV, which were used as surrogate viruses for human pathogenic enveloped viruses. The quantitative suspension test was used. A solution containing 12% EO + 10% OH reduced > 4.0 log10 TCID50 (100% reduction) of both viruses within 1 min of exposure. In addition, solutions containing 12% EO and 3% EO without OH reduced > 4.0 log10 TCID50 of both viruses after 10 min and 30 min of exposure, respectively. The binding affinities of 42 EO compounds and viral envelope proteins were investigated through docking analyses. Sesquiterpene showed the highest binding affinities (from −6.7 to −8.0 kcal/mol) with DENV-2 E and CHIKV E1-E2-E3 proteins. The data provide a first step toward defining the potential of EOs as disinfectants.

Microbial infections resistant to conventional antibiotics constitute one of the most important causes of mortality in the world. In some bacterial species, such as Escherichia coli and Staphylococcus aureus pathogens, biofilm formation can favor their antimicrobial resistance. These biofilm-forming bacteria produce a compact and protective matrix, allowing their adherence and colonization to different surfaces, and contributing to resistance, recurrence, and chronicity of the infections. Therefore, different therapeutic alternatives have been investigated to interrupt both cellular communication routes and biofilm formation. Among these, essential oils (EO) from Lippia origanoides thymol-carvacrol II chemotype (LOTC II) plants have demonstrated biological activity against different biofilm-forming pathogenic bacteria. In this work, we determined the effect of LOTC II EO on the expression of genes associated with quorum sensing (QS) communication, biofilm formation, and virulence of E. coli ATCC 25922 and S. aureus ATCC 29213. This EO was found to have high efficacy against biofilm formation, decreasing—by negative regulation—the expression of genes involved in motility (fimH), adherence and cellular aggregation (csgD), and exopolysaccharide production (pgaC) in E. coli. In addition, this effect was also determined in S. aureus where the L. origanoides EO diminished the expression of genes involved in QS communication (agrA), production of exopolysaccharides by PIA/PNG (icaA), synthesis of alpha hemolysin (hla), transcriptional regulators of the production of extracellular toxins (RNA III), QS and biofilm formation transcriptional regulators (sarA) and global regulators of biofilm formation (rbf and aur). Positive regulation was observed on the expression of genes encoding inhibitors of biofilm formation (e.g., sdiA and ariR). These findings suggest that LOTCII EO can affect biological pathways associated with QS communication, biofilm formation, and virulence of E. coli and S. aureus at subinhibitory concentrations and could be a promising candidate as a natural antibacterial alternative to conventional antibiotics.

Nontyphoidal Salmonella species are one of the main bacterial causes of foodborne diseases, causing a public health problem. In addition, the ability to form biofilms, multiresistance to traditional drugs, and the absence of effective therapies against these microorganisms are some of the principal reasons for the increase in bacterial diseases. In this study, the anti-biofilm activity of twenty essential oils (EOs) on Salmonella enterica serovar Enteritidis ATCC 13076 was evaluated, as well as the metabolic changes caused by Lippia origanoides thymol chemotype EO (LOT-II) on planktonic and sessile cells. The anti-biofilm effect was evaluated by the crystal violet staining method, and cell viability was evaluated through the XTT method. The effect of EOs was observed by scanning electron microscopy (SEM) analysis. Untargeted metabolomics analyses were conducted to determine the effect of LOT-II EO on the cellular metabolome. LOT-II EO inhibited S. Enteritidis biofilm formation by more than 60%, without decreasing metabolic activity. Metabolic profile analysis identified changes in the modulation of metabolites in planktonic and sessile cells after LOT-II EO treatment. These changes showed alterations in different metabolic pathways, mainly in central carbon metabolism and nucleotide and amino acid metabolism. Finally, the possible mechanism of action of L. origanoides EO is proposed based on a metabolomics approach. Further studies are required to advance at the molecular level on the cellular targets affected by EOs, which are promising natural products for developing new therapeutic agents against Salmonella sp. strains.

Carnosol is a natural diterpene present in Rosmarinus officinalis L. (rosemary) with anti-tumor and anti-inflammatory properties. Despite its importance, the pharmacological mechanisms underlying the interactions between carnosol and human targets are still unclear. The goal was to identify plausible human target for carnosol and the network pharmacology. Rosemary was analyzed using HPLC-QTOF-MS/MS. Potential carnosol targets were identified using docking and a public database (CTD). Carnosol was screened against 708 human proteins using AutoDock Vina, and affinity values were used as prioritization criteria. The targets set was uploaded to WebGestalt to obtain Gene Ontology (GO) and KEGG pathway enrichment analysis. HPLC-QTOF-MS/MS analyses allowed the tentative annotation of nine chemicals, with carnosol being the most ionized. There were 53 plausible targets for carnosol, with 20 identified using virtual screening, including Hsp90α (−10.9 kcal/mol), AKR1C3 (−10.4 kcal/mol), and Hsp90β (−10.4 kcal/mol), and 33 identified from CTD. The potential targets for carnosol identified with PPI and molecular docking were HSP90AA1, MAPK1, MAPK3, CAT, JUN, AHR, and CASP3. GO terms and KEGG pathways analysis found that carnosol is closely related to infection (Chagas, influenza A, toxoplasmosis, and pertussis) and inflammation (IL-17 and TNF signaling pathway and Th-17 cell differentiation). These results demonstrated that carnosol may induce an immuno-inflammatory response.

Bacteria can communicate through quorum sensing, allowing them to develop different survival or virulence traits that lead to increased bacterial resistance against conventional antibiotic therapy. Here, fifteen essential oils (EOs) were investigated for their antimicrobial and anti-quorum-sensing activities using Chromobacterium violaceum CV026 as a model. All EOs were isolated from plant material via hydrodistillation and analyzed using GC/MS. In vitro antimicrobial activity was determined using the microdilution technique. Subinhibitory concentrations were used to determine anti-quorum-sensing activity by inhibition of violacein production. Finally, a possible mechanism of action for most bioactive EOs was determined using a metabolomic approach. Among the EOs evaluated, the EO from Lippia origanoides exhibited antimicrobial and anti-quorum activities at 0.37 and 0.15 mg/mL, respectively. Based on the experimental results, the antibiofilm activity of EO can be attributed to the blockage of tryptophan metabolism in the metabolic pathway of violacein synthesis. The metabolomic analyses made it possible to see effects mainly at the levels of tryptophan metabolism, nucleotide biosynthesis, arginine metabolism and vitamin biosynthesis. This allows us to highlight the EO of L. origanoides as a promising candidate for further studies in the design of antimicrobial compounds against bacterial resistance.

Cymbopogon nardus (citronella) essential oil (EO) has been widely used in the cosmetic and food industry due to its repellent and fumigant properties. The aim of this study was to evaluate its effects on the life cycle and midgut morphology of the natural predator Ceraeochrysa claveri. Larvae were fed on sugarcane borer eggs (Diatraea saccharalis) pretreated with citronella EO solutions (1–100 µg/mL in methanol, 5 s) or solvent and air-dried at room temperature for 30 min. Larval and pupal stage duration, the percentage of emergence of the insect, and malformed insects were recorded. One day after adults emerged from their cocoons, adult insects were used to obtain their midgut and analyzed using light microscopy. The chemical composition of C. nardus EO revealed that citronellal (25.3%), citronellol (17.9%), geraniol (11.6%), elemol (6.5%), δ-cadinone (3.6%), and germacrene D (3.4%) were the predominant compounds. Exposure to the EO produced a significant change in development duration for third instar and prepupa of the insect. The observed alterations in the lifecycle included prepupae with no cocoon formation, dead pupa inside the cocoon, and malformed adults. Several injuries in the midgut epithelium of exposed adults were registered, such as detachment of columnar cells leaving only swollen regenerative cells fixed on the basement membrane, and the formation of epithelial folds. In summary, these data suggest that C. nardus oil has adverse effects on the life cycle and midgut morphology of a beneficial predator.

Plants of the genus Scutellaria (Lamiaceae) have a wide variety of bioactive secondary metabolites with diverse biological properties, e.g., anti-inflammatory, antiallergenic, antioxidant, antiviral, and antitumor activities. The chemical composition of the hydroethanolic extracts, obtained from dried plants of S. incarnata, S. coccinea, and S. ventenatii × S. incarnata, was determined by UHPLC/ESI-Q-Orbitrap-MS. The flavones were found in a higher proportion. Baicalin and dihydrobaicalein-glucuronide were the major extract components in S. incarnata (287.127 ± 0.005 mg/g and 140.18 ± 0.07 mg/g), in S. coccinea (158.3 ± 0.34 mg/g and 51.20 ± 0.02 mg/g), and in S. ventenatii × S. incarnata (186.87 ± 0.01 mg/g and 44.89 ± 0.06 mg/g). The S. coccinea extract showed the highest antioxidant activity in the four complementary techniques employed to evaluate all extracts: ORAC (3828 ± 3.0 µmol Trolox®/g extract), ABTS+• (747 ± 1.8 µmol Trolox®/g extract), online HPLC-ABTS+• (910 ± 1.3 µmol Trolox®/g extract), and β-carotene (74.3 ± 0.8 µmol Trolox®/g extract).

Most Candida species are opportunistic pathogens with the ability to form biofilms, which increases their resistance to antifungal drug therapies and the host immune response. Essential oils (EOs) are an alternative for developing new antimicrobial drugs, due to their broad effect on cellular viability, cell communication, and metabolism. In this work, we evaluated the antifungal and antibiofilm potential of fifty EOs on C. albicans ATCC 10231, C. parapsilosis ATCC 22019, and Candida auris CDC B11903. The EOs’ antifungal activity was measured by means of a broth microdilution technique to determine the minimum inhibitory and fungicidal concentrations (MICs/MFCs) against the different Candida spp. strains. The effects on biofilm formation were determined by a crystal violet assay using 96-well round-bottom microplates incubated for 48 h at 35 °C. The EOs from Lippia alba (Verbenaceae family) carvone-limonene chemotype and L. origanoides exhibited the highest antifungal activity against C. auris. The L. origanoides EOs also presented antifungal and antibiofilm activity against all three Candida spp., thus representing a promising alternative for developing new antifungal products focused on yeast infections, especially those related to biofilm formation, virulence factors, and antimicrobial resistance.

The study aimed to determine the enhanced effects of essential oils (EOs) and plant-derived molecules (PDMs) as penetration enhancers (PEs) for transdermal drug delivery (TDD) of caffeine. A 1% w/w solution of eight EOs and seven PDMs was included in the 1% caffeine carbopol hydrogel. Franz diffusion cell experiments were performed using mice with full-thickness skin. At various times over 24 h, 300 μL of the receptor were withdrawn and replaced with fresh medium. Caffeine was analyzed spectrophotometrically at 272 nm. The skin irritation effects of the hydrogels applied once a day for 21 days were investigated in mice. The steady-state flux (JSS) of the caffeine hydrogel was 30 ± 19.6 µg cm−2 h−1. An increase in caffeine JSS was induced by Lippia origanoides > Turnera diffusa > eugenol > carvacrol > limonene, with values of 150 ± 14.1, 130 ± 47.6, 101 ± 21.7, 90 ± 18.4, and 86 ± 21.0 µg cm−2 h−1, respectively. The Kp of caffeine was 2.8 ± 0.26 cm h−1, almost 2–4 times lower than that induced by Lippia origanoides > Turnera diffusa > limonene > eugenol > carvacrol, with Kp values of 11 ± 1.7, 8.8 ± 4.2, 6.8 ± 1.7, 6.3 ± 1.2, and 5.15 ± 1.0 cm h−1, respectively. No irritating effects were observed. Lippia origanoides, Turnera diffusa, eugenol, carvacrol, and limonene improved caffeine’s skin permeation. These compounds may be as effective as the PE in TDD systems.

Стаття присвячена актуальним питанням розвитку глобального ринку транспортно-логістичних послуг які визначається цілою низкою обставин. Проаналізовано прискорення процесів взаємодії всіх галузей економіки, які провокують транспортний сектор на постійні поліпшення. Досліджено транспортний сектор, який є одним з основних факторів глобалізації як міжнародної торгівлі, так і транснаціональних компаній, оскільки розвиток міжнародних та внутрішніх ринків у всі часи супроводжувався вільним переміщенням товарів та ресурсів. Розглянуто суперечливі тенденції інфраструктурного сектору та залежність транспорту від галузей матеріальних благ. Окреслено резерви впливу на регіональний розподіл виробничих потужностей, які беруть участь у процесі відтворення і виступають у ролі одного з основних елементів системи економічних відносин.

Hibiscus rosa-sinensis plants are mainly cultivated as ornamental plants, but they also have food and medicinal uses. In this work, 16 H. rosa-sinensis cultivars were studied to measure their colorimetric parameters and the chemical composition of hydroethanolic extracts obtained from their petals. These extracts were characterized using UHPLC-ESI+-Obitrap-MS, and their antioxidant activity was evaluated using the ORAC assay. The identified flavonoids included anthocyanins derived from cyanidin, glycosylated flavonols derived from quercetin and kaempferol, and flavan-3-ols such as catechin and epicatechin. Cyanidin-sophoroside was the anthocyanin present in extracts of lilac, pink, orange, and red flowers, but was not detected in extracts of white or yellow flowers. The total flavonol concentration in the flower extracts was inversely proportional to the total anthocyanin content. The flavonol concentration varied according to the cultivar in the following order: red < pink < orange < yellow ≈ white, with the extract from the red flower presenting the lowest flavonol concentration and the highest anthocyanin concentration. The antioxidant activity increased in proportion to the anthocyanin concentration, from 1580 µmol Trolox®/g sample (white cultivar) to 3840 µmol Trolox®/g sample (red cultivar).

The essential oils (EOs) from bioactive species can provide an alternative tool for the management of stored grain insects that is less environmentally damaging than synthetic chemicals. The aim of this study was to assess the repellent action and toxicity of EOs obtained from phellandrene-rich Lippia origanoides, carvone-rich Lippia alba, citral-rich L. alba, and Pogostemon cablin aerial parts on adults of Ulomoides dermestoides. These EOs were isolated by hydrodistillation and characterized by gas chromatography coupled to mass spectrometry (GC-MS). The repellency assay was carried out using the area preference method, and the toxicity evaluated utilizing a filter paper contact test. The major components (>10%) of the studied EOs were sabinene (16.9%), trans-β-caryophyllene (18.6%) and α-humulene (10.1%) for phellandrene-rich L. origanoides EO; limonene (40.1%) and carvone (37.7%) for carvone-rich L. alba EO; geranial (24.5%), geraniol (19.0%), and neral (11.9%) for citral-rich L. alba EO; and α-guaiene (13.3%), α-bulnesene (15.7%), and patchoulol (35.3%) for P. cablin EO. All EOs displayed 100% repellency at a concentration of 16 μL/mL, with lower toxicity than that elicited by the commercial repellent DEET. EO concentrations up to 8 µL/mL did not induce any mortality on the beetle. These findings show that the EOs provide active and safe molecules for natural repellent formulations to prevent and control insect infestations of stored products.

ABSTRACT: This research described an efficient micropropagation protocol for Lippia origanoides (Verbenaceae). Sterile seeds were used to obtain germinated seedlings in Murashige and Skoog medium (MS) supplemented with sucrose and agar. The nodal segments obtained from seedlings were grown on MS medium supplemented with different concentrations of gibberellic acid (GA), benzylaminopurine (BAP) and 1-naphthalenacetic acid (NAA) with BAP. The callus induction, shoots length, shoots number and root length, were analyzed. The treatments showed high percentage of callus formation at 0.5 to 1.5 mg L-1 of BAP alone or in combination with NAA (0.1 mg L-1). The highest value of shoot number per nodal segments was obtained at 1.5 mg L-1 of BAP (4.3 ± 0.8). The obtained plantlets were better rooted in vitro in the absence of plant growth regulators (PGRs) and they showed acclimatization rate of 90%. We reported a protocol for in vitro propagation and acclimatization of L. origanoides for A chemotypes from Colombia.

Multi-drug resistant species such as Candida auris are a global health threat. This scenario has highlighted the need to search for antifungal alternatives. Essential oils (EOs), or some of their major compounds, could be a source of new antifungal molecules. The aim of this study was to evaluate the in vitro activity of EOs and some terpenes against C. auris and other Candida spp. The eleven EOs evaluated were obtained by hydro-distillation from different Colombian plants and the terpenes were purchased. EO chemical compositions were obtained by gas chromatography/mass spectrometry (GC/MS). Antifungal activity was evaluated following the CLSI standard M27, 4th Edition. Cytotoxicity was tested on the HaCaT cell line and fungal growth kinetics were tested by time–kill assays. Candida spp. showed different susceptibility to antifungals and the activity of EOs and terpenes was strain-dependent. The Lippia origanoides (thymol + p-cymene) chemotype EO, thymol, carvacrol, and limonene were the most active, mainly against drug-resistant strains. The most active EOs and terpenes were also slightly cytotoxic on the HaCaT cells. The findings of this study suggest that some EOs and commercial terpenes can be a source for the development of new anti-Candida products and aid the identification of new antifungal targets or action mechanisms.

Currently, there are no therapies to prevent severe dengue disease. Essential oils (EOs) can serve as primary sources for research and the discovery of phytomedicines for alternative therapy. Fourteen EOs samples were obtained by distillation from six plants used in Colombian folk medicine. GC/MS analysis identified 125 terpenes. Cytopathic effect (CPE) reduction assays revealed differences in antiviral activity. EOs of Lippia alba, citral chemotype and carvone-rich fraction; Lippia origanoides, phellandrene chemotype; and Turnera diffusa, exhibited strong antiviral activity (IC50: 29 to 82 µg/mL; SI: 5.5 to 14.3). EOs of Piper aduncum, Ocimum basilicum, and L. origanoides, carvacrol, and thymol chemotypes, exhibited weak antiviral activity (32 to 53% DENV-CPE reduction at 100 µg/mL; SI > 5.0). Cluster and one-way ANOVA analyses suggest that the strong antiviral activity of EOs could be attributed to increased amounts of non-phenolic oxygenated monoterpenes and sesquiterpene hydrocarbons. Docking analyses (AutoDock Vina) predicted binding affinity between the DENV-2 E protein and terpenes: twenty sesquiterpene hydrocarbons (−8.73 to −6.91 kcal/mol), eight oxygenated monoterpenes (−7.52 to −6.98 kcal/mol), and seven monoterpene hydrocarbons (−7.60 to −6.99 kcal/mol). This study reports for the first time differences in the antiviral activity of EOs against DENV, corresponding to their composition of monoterpenes and sesquiterpenes.

Land-use change and pesticides have been identified as two of the main causes behind pollinator decline. Understanding how these factors affect crop pollinator communities is crucial to inform practices that generate optimal pollination and ensure sustainable food production. In this study, we investigated the effects of landscape composition and pesticide residues on bee communities and their pollination services in Solanum quitoense Lam. “lulo” crops in Colombia. On 10 farms, located along a gradient of land use change that varied from 0.15 to 0.62 in their natural habitat proportion, we characterized the bee community visiting the crop, and carried out pollination experiments with bagged and open inflorescences to later estimate fruit set, weight, and diameter at every site. Additionally, we performed pesticide analysis on collected anthers through liquid chromatography to estimate pesticide risk coming from the crop fields using hazard quotients (HQ). Bee abundance and species richness decreased with increased HQ, but these negative pesticide effects were less detrimental in farms with higher natural habitat proportions. However, this buffer effect was lost at sites with very high HQs. Imidacloprid was frequently found in the anthers and there were extremely high concentrations in some farms (0.6 to 13,063 μg/kg), representing the molecule of greatest risk for bees in this context. Pollinator’s importance to crop yield was demonstrated in the exclusion experiments, where we found a reduction in fruit set (51%), weight (39%), and diameter (25%). We found a significant effect of bee richness on fruit set, while landscape composition and HQ had no significant effect on fruit set, suggesting that the last two factors do not affect yield directly, but indirectly through a decrease in pollinator diversity. Our results provide novel evidence that natural habitat loss due to the expansion of pastures for cattle ranching and pesticide residues in anthers reduce bee diversity and abundance in this Andean cropping system, but strategies to protect and restore natural habitat can help to buffer, until certain levels, these negative effects.

Plants are sources of sunscreen ingredients that prevent cellular mutations involved in skin cancer and aging. This study investigated the sunscreen properties of the extracts from some ornamental plants growing in Colombia. The UV filter capability of the flower extracts obtained from Rosa centifolia L., Posoqueria latifolia (Rudge) Schult, and Ipomoea horsfalliae Hook. was examined. Photoprotection efficacies were evaluated using in vitro indices such as sun protection factor and critical wavelength. UVB antigenotoxicity estimates measured with the SOS Chromotest were also obtained. Extract cytotoxicity and genotoxicity were studied in human fibroblasts using the trypan blue exclusion and Comet assays, respectively. Major compounds of the promising flower extracts were identified by UHPLC–ESI+–Orbitrap–MS. The studied extracts showed high photoprotection efficacy and antigenotoxicity against UVB radiation, but only the P. latifolia extract showed broad-spectrum photoprotection at non-cytotoxic concentrations. The P. latifolia extract appeared to be safer for human fibroblast cells and the R. centifolia extract was shown to be moderately cytotoxic and genotoxic at the highest assayed concentrations. The I. horsfalliae extract was unequivocally cytotoxic and genotoxic. The major constituents of the promising extracts were as follows: chlorogenic acid, ecdysterone 20E, rhamnetin-rutinoside, cis-resveratrol-diglucoside, trans-resveratrol-diglucoside in P. latifolia; quercetin, quercetin-glucoside, quercetin-3-rhamnoside, kaempferol, kaempferol-3-glucoside, and kaempferol-rhamnoside in R. centifolia. The potential of the ornamental plants as sources of sunscreen ingredients was discussed.

In this work, the antioxidant activity of the hydro-ethanolic extracts of the leaves, flowers, and aerial parts of Steiractinia aspera Cuatrec, both fresh and post-distillation, was evaluated by ABTS+·, FRAP, H2O2 and DPPH assays. The cytotoxic activity was evaluated in MCF-7, MCF-10A and HT-29 cell lines. The hydro-ethanolic extracts were obtained by matrix solid-phase dispersion (MSPD) and ultrasound-assisted solvent extraction (SE). The fresh-leaf MSPD extract had the highest antioxidant activity, and the post-distillation leaf ultrasound-assisted SE extract had the highest cytotoxicity in the MCF-7 breast cancer cell line, although not selective, which was evaluated by sulforhodamine B assay. On the other hand, ROS was evaluated by flow cytometry which showed that post-distillation leaf extract is pro-oxidant. Chlorogenic acid, kaempferol-3-glucoside and quercetin were found in the fresh leaves’ extracts, according to HPLC-DAD. PLC-DAD permitted the isolation of p-coumaric acid, E-3-(4-(((E)-3-(3,4-dihydroxyphenyl) acryloyl) oxy)-3-hydroxyphenyl) acrylic acid and a diglucosylated derivative of ursolic acid, which were analyzed by 1H and 13C NMR. Our results suggest that the fresh leaf extract of Steiractinia aspera Cuatrec has potential use for antioxidant applications.

Photoprotective agents obtained from plants provide benefits for the health of the skin. The present study aims to assess the total phenolic content (TPC) and in vitro UV-protective properties of twelve essential oils (EOs) from plants grown in Colombia and to evaluate the antioxidant and cytotoxic potential of two species identified as photoprotective potentials: Cymbopogon flexuosus and Tagetes lucida. The composition of EOs was studied by GC/MS. The cytotoxicity of both EOs was examined using an MTT assay, and an H2-DCFDA probe was employed to estimate the intracellular production of ROS in HepG2 and Calu-1 cells. Major constituents (≥10%) were neral, geranial, geranyl acetate in C. flexuosus and estragole in T. lucida. The TPC for C. flexuosus and T. lucida EOs were ≥10 mg GAE/g of byproduct. Both EOs showed photoprotective properties (SPFin vitro: 13–14), and long-wavelength UVA protection (λc > 370 nm). HepG2 and Calu-1 cells exposed to C. flexuosus exhibited antiproliferative activity (˂50%) at 125 µg/mL, while T. lucida was at 250 and 500 µg/mL. The IC50 values for C. flexuosus were 75 and 100 µg/mL in HepG2 and Calu-1 cells, respectively, whereas those for T. lucida were >250 µg/mL. These EOs achieved significant inhibitory effects (between 15.6 and 40.4%) against H2O2-induced oxidative stress. The results showed that EO compounds recognized as antioxidants could counteract the effects elicited by H2O2.

Eleven species of lichens of the genus Sticta, ten of which were collected in Colombia (S. pseudosylvatica S. luteocyphellata S. cf. andina S. cf. hypoglabra, S. cordillerana, S. cf. gyalocarpa S. leucoblepharis, S. parahumboldtii S. impressula, S. ocaniensis) and one collected in Chile (S. lineariloba), were analyzed for the first time using hyphenated liquid chromatography with high-resolution mass spectrometry. In the metabolomic analysis, a total of 189 peaks were tentatively detected; the analyses were divided in five (5) groups of compounds comprising lipids, small phenolic compounds, saturated acids, terpenes, and typical phenolic lichen compounds such as depsides, depsidones and anthraquinones. The metabolome profiles of these eleven species are important since some compounds were identified as chemical markers for the fast identification of Sticta lichens for the first time. Finally, the usefulness of chemical compounds in comparison to traditional morphological traits to the study of ancestor–descendant relationships in the genus was assessed. Chemical and morphological consensus trees were not consistent with each other and recovered different relationships between taxa.

Abstract Background Chagas Disease caused by Trypanosoma cruzi infection, is one of the most important neglected tropical diseases (NTD), without an effective therapy for the successful parasite eradication or for the blocking of the disease’s progression, in its advanced stages. Due to their low toxicity, wide pharmacologic spectrum, and potential synergies, medicinal plants as Lippia alba, offer a promising reserve of bioactive molecules. The principal goal of this work is to characterize the inhibitory properties and cellular effects of the Citral and Carvone L. alba chemotype essential oils (EOs) and their main bioactive terpenes (and the synergies among them) on T. cruzi forms. Methods Twelve L. alba EOs, produced under diverse environmental conditions, were extracted by microwave assisted hydrodistillation, and chemically characterized using gas chromatography coupled mass spectrometry. Trypanocidal activity and cytotoxicity were determined for each oil, and their major compounds, on epimastigotes (Epi), trypomastigotes (Tryp), amastigotes (Amas), and Vero cells. Pharmacologic interactions were defined by a matrix of combinations among the most trypanocidal terpenes (limonene, carvone; citral and caryophyllene oxide). The treated cell phenotype was assessed by fluorescent and optic microscopy, flow cytometry, and DNA electrophoresis assays. Results The L. alba EOs displayed significant differences in their chemical composition and trypanocidal performance (p = 0.0001). Citral chemotype oils were more trypanocidal than Carvone EOs, with Inhibitory Concentration 50 (IC50) of 14 ± 1.5 μg/mL, 22 ± 1.4 μg/mL and 74 ± 4.4 μg/mL, on Epi, Tryp and Amas, respectively. Limonene exhibited synergistic interaction with citral, caryophyllene oxide and Benznidazole (decreasing by 17 times its IC50) and was the most effective and selective treatment. The cellular analysis suggested that these oils or their bioactive terpenes (citral, caryophyllene oxide and limonene) could be inducing T. cruzi cell death by an apoptotic-like mechanism. Conclusions EOs extracted from L. alba Citral chemotype demonstrated significant trypanocidal activity on the three forms of T. cruzi studied, and their composition and trypanocidal performance were influenced by production parameters. Citral, caryophyllene oxide, and limonene showed a possible induction of an apoptotic-like phenotype. The best selective anti-T. cruzi activity was achieved by limonene, the effects of which were also synergic with citral, caryophyllene oxide and benznidazole.