Chemical Profile and Biological Potential of Scaptotrigona Bee Products (Hymenoptera, Apidae, Meliponini): An Review.

Stingless bees belong to the Meliponini tribe and are widely distributed in the tropics and subtropics, where they perform important ecological services. Among the best distributed groups of stingless bees is the genus Scaptotrigona, which includes 22 species distributed throughout the neotropical region, including the area from Mexico to Argentina. Bees of this genus are responsible for the production of products such as honey, propolis, geopropolis and fermented pollen ("saburá"). This review aimed to provide an overview of the chemical composition and biological activities associated with derived products from stingless bees of the genus Scaptotrigona. The bibliographic review was carried out through searches in the Scopus, Web of Science, ScienceDirect and PubMed databases, including publications from 2003 to January 2023. The study of the chemodiversity of products derived from Scaptotrigona demonstrated the mainly presence of flavonoids, phenolic acids, terpenoids and alkaloids. It was also demonstrated that products derived from bees of the genus Scaptotrigona exhibit a wide range of biological effects, such as antibacterial, antioxidant, anti-inflammatory and antifungal activities, among other bioactivities. This review provides an overview of phytochemical and pharmacological investigations of the genus Scaptotrigona. However, it is essential to clarify the toxicity and food safety of these products.

Floral Visitation, Phytochemical and Biological Activities of Bioproducts from Tetragonisca angustula (Hymenoptera, Apidae, Meliponini): A Review.

Tetragonisca angustula (Latreille, 1811) is an indigenous neotropical stingless bee, popularly known as "Jataí", with a wide distribution in the Brazilian territory. T. angustula produces other derivatives such as propolis, geopropolis, fermented (saburá pollen), cerumen and resins, which are important in folk medicine. In this review, the objective was to gather research on the main plant species visited by T. angustula, as well as studies that verified the chemical composition and biological properties of T. angustula bioproducts. The bibliographic review was performed by searching the Scopus, Web of Science, ScienceDirect, and PubMed databases for publications from 2003 to February 2023. We found 78 studies that analyzed the interactions between T. angustula and floral species, with species from the botanical families Fabaceae, Asteraceae, Malvaceae, Bignoniaceae, Solanaceae, Myrtaceae and Lamiaceae being the most reported as the main food sources for this species. The presence of compounds belonging to the class of flavonoids, phenolic acids, terpenoids and alkaloids has been identified by studying the chemical composition of honey, propolis, geopropolis and fermented pollen (saburá) in 21 studies. The data collected in the literature emphasize that these T. angustula products have remarkable biological properties, especially their antibacterial and antioxidant activities.

Evaluation of the antibacterial and inhibitory activity of the MepA efflux pump of Staphylococcus aureus by riparins I, II, III, and IV.

The efflux pump mechanism contributes to the antibiotic resistance of widely distributed strains of Staphylococcus aureus. Therefore, in the present work, the ability of the riparins N-(4-methoxyphenethyl)benzamide (I), 2-hydroxy-N-[2-(4-methoxyphenyl)ethyl]benzamide (II), 2, 6-dihydroxy-N-[ 2-(4-methoxyphenyl)ethyl]benzamide (III), and 3,4,5-trimethoxy-N-[2-(4-methoxyphenethyl)benzamide (IV) as potential inhibitors of the MepA efflux pump in S. aureus K2068 (fluoroquinolone-resistant). In addition, we performed checkerboard assays to obtain more information about the activity of riparins as potential inhibitors of MepA efflux and also analyzed the ability of riparins to act on the permeability of the bacterial membrane of S. aureus by the fluorescence method with SYTOX Green. A molecular coupling assay was performed to characterize the interaction between riparins and MepA, and ADMET (absorption, distribution, metabolism, and excretion) properties were analyzed. We observed that I-IV riparins did not show direct antibacterial activity against S. aureus. However, combination assays with substrates of MepA, ciprofloxacin, and ethidium bromide (EtBr) revealed a potentiation of the efficacy of these substrates by reducing the minimum inhibitory concentration (MIC). Furthermore, increased EtBr fluorescence emission was observed for all riparins. The checkerboard assay showed synergism between riparins I, II, and III, ciprofloxacin, and EtBr. Furthermore, riparins III and IV exhibited permeability in the S. aureus membrane at a concentration of 200 µg/mL. Molecular docking showed that riparins I, II, and III bound in a different region from the binding site of chlorpromazine (standard pump inhibitor), indicating a possible synergistic effect with the reference inhibitor. In contrast, riparin IV binds in the same region as the chlorpromazine binding site. From the in silico ADMET prediction based on MPO, it could be concluded that the molecules of riparin I-IV present their physicochemical properties within the ideal pharmacological spectrum allowing their preparation as an oral drug. Furthermore, the prediction of cytotoxicity in liver cell lines showed a low cytotoxic effect for riparins I-IV.

Antibacterial and Toxic Activity of Geopropolis Extracts from Melipona subnitida (Ducke, 1910) (Hymenoptera: Apidae) and Scaptotrigona depilis (Moure, 1942) (Hymenoptera: Apidae).

Bacteria are associated with many infections that affect humans and present antibiotic resistance mechanisms, causing problems in health organisations and increased mortality rates. Therefore, it is necessary to find new antibacterial agents that can be used in the treatment of these microorganisms. Geopropolis is a natural product from stingless bees, formed by a mixture of plant resins, salivary secretions, wax and soil particles, the chemical composition of this natural product is diverse. Thus, this study aimed to evaluate antibacterial activity, antibiotic modulation and the toxicity of geopropolis extracts from the stingless bees, Melipona subnitida (Ducke, 1910) and Scaptotrigona depilis (Moure, 1942) against standard and multi-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacteria. Geopropolis samples were collected in a meliponary located in Camaragibe, Pernambuco, Brazil. To determine the Minimum Inhibitory Concentration (MIC) and antibiotic modulation we performed broth microdilution tests. Mortality tests were used to verify extract toxicity in the model Drosophila melanogaster. The microbiological tests showing that the M. subnitida extracts had better inhibitory effects compared to S. depilis, presenting direct antibacterial activity against standard and multi-resistant strains. The extracts potentialized antibiotic effects, suggesting possible synergy and did not present toxicity in the model used. The information obtained in this study highlights extracts as promising antibacterial agents and is the first study to evaluate bacterial activity in these extracts, in addition to verifying their modulating effects and determining toxicity in the model used.

Antibacterial activity of eugenol on the IS-58 strain of Staphylococcus aureus resistant to tetracycline and toxicity in Drosophila melanogaster.

The indiscriminate use of antibiotics contributes significantly to the selection of bacteria resistant to several antibiotics. Among the resistance mechanisms are the Efflux Pumps which are responsible for extruding solutes from the cell cytoplasm through proteins in the cell membrane. Because of this, new strategies are needed to control multidrug-resistant pathogenic strains. In this way, the objective of this study was to evaluate the antibacterial activity of eugenol by inhibition of TetK Efflux Pump in strains of Staphylococcus aureus resistant to Tetracycline, in addition to evaluating its toxicity in Drosophila melanogaster. To determine the Minimum Inhibitory Concentration (MIC), the broth microdilution method was used. The modulated effect of antibiotic and Ethidium Bromide associated with eugenol in subinhibitory concentrations (MIC/8) was evaluated. To evaluate the toxic effect of eugenol on D. melanogaster, fumigation tests were used, in which the parameters of mortality and damage to the locomotor system were evaluated. The results showed that eugenol has no direct activity in S. aureus, with an MIC ≥1024 µg/mL. However, it demonstrated that the synergistic potential when associated with Tetracycline, reducing the MIC of the antibiotic, already associated with Ethidium Bromide, had an antagonistic effect. When the toxicity in D. melanogaster was evaluated, eugenol demonstrated a non-toxic profile, since it presented EC50: 2036 µL/mL in 48 h of exposure. In conclusion, eugenol had no relevant direct effect against S. aureus, however, it potentialized the action of the antibiotic by decreasing its MIC.

Effect of terpinolene against the resistant Staphylococcus aureus strain, carrier of the efflux pump QacC and ß-lactamase gene, and its toxicity in the Drosophila melanogaster model.

Efflux pumps and ß-lactamases are mechanisms of bacterial resistance that exist in Staphylococcus aureus, where both mechanisms are expressed simultaneously in the SA K4100 strain, with its efflux pump being characterized as QacC (Quaternary Ammonium Compounds C). The search for inhibitors of these mechanisms has grown gradually, with research on isolated compounds, including terpenes, which have innumerable biological activities, being common. This study sought to evaluate the antibacterial activity of Terpinolene against the S. aureus K4100 strain, carrying a QacC efflux pump and ß-lactamase, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. Determination of the Minimum Inhibitory Concentration (MIC) was performed by broth microdilution. Efflux pump inhibition was evaluated by the MIC reduction of Oxacillin and Ethidium Bromide (EtBr). ß-Lactamase inhibition was analyzed by the MIC reduction of Ampicillin with Sulbactam. Toxicity was verified by mortality parameters and locomotor assays in D. melanogaster. The results demonstrated that Terpinolene did not present a direct antibacterial activity (MIC ≥ 1024 µg/mL). However, a reduction in MIC was observed when Terpinolene was associated with Oxacillin (161.26-71.83 µg/mL) and EtBr (45.25-32 µg/mL), possibly by a ß-lactamase and efflux pump inhibition, thus evidencing a modulatory activity. Terpinolene presented D. melanogaster mortality with an EC50 of 34.6 µL/L within 12 h of exposure. Additionally, Terpinolene presented damage to the locomotor system after the second hour of exposure, with the effect increasing in a concentration-dependent manner. In conclusion, new tests should be carried out to investigate the Terpinolene reinforcement of antibiotic activity and toxic activity mechanisms of action.

Mesosphaerum suaveolens (L. ) Kuntze (bamburral) planta medicinal com potencial antioxidante e rica em polifenóis / Mesosphaerum suaveolens (L.) Kuntze (pignut) a medicinal plant with antioxidant potential and abundant polyphenols

Introducción: Mesosphaerum suaveolens (L.) Kuntze (Lamiaceae), planta conocida como bamburral, se utiliza en la medicina popular; sin embargo, poco se sabe de sus componentes químicos, sus efectos tóxicos y sus propiedades terapéuticas. Objetivo: Caracterizar los compuestos polifenólicos de los extractos de M. suaveolens, así como su actividad antioxidante y tóxica. Métodos: Se analizaron los componentes químicos de los extractos acuoso y etanólico de las hojas frescas mediante HPLC-DAD, la actividad antioxidante de los extractos en diversas concentraciones (entre 4 y 1024 µg/mL) frente al radical libre DPPH acompañado de un control positivo (ácido ascórbico) y se evaluó la actividad tóxica de los extractos contra Artemia salina. Resultados: Los resultados indican que los extractos acuoso y etanólico tienen como compuesto mayoritario el ácido cafeico (13.27 y 15.09 mg/g, respectivamente). Los extractos posee elevada actividad antioxidante con concentración de inhibición al 50 % (IC50) de 7.06 µg/mL para el extracto etanólico, 20.32 µg/mL para el acuoso y 6.69 µg/mL para el ácido ascórbico. Ninguno de los extractos presentó toxicidad con el método analizado (p> 0,05). Conclusiones: Por lo tanto, se demuestra que los extractos no presentan toxicidad, pero presentan una gran capacidad para eliminar los radicales libres en el organismo y son una fuente natural para fabricar medicamentos.

Introduction: The species Mesosphaerum suaveolens (L.) Kuntze (Lamiaceae), commonly known as pignut, is used in folk medicine. However, little information is available about its chemical components, toxic effects and therapeutic properties. Objective: Characterize the polyphenolic compounds contained in M. suaveolens extracts, as well as their antioxidant and toxic activity. Methods: The chemical components of aqueous and ethanolic fresh leaf extracts were analyzed by HPLC-DAD. Evaluation was performed of the antioxidant activity of the extracts against DPPH free radical at various concentrations (between 4 and 1 1024 µg/ml) accompanied by a positive control (ascorbic acid), as well as their toxic activity against Artemia salina. Results: Caffeic acid is the most abundant compound in the aqueous and the ethanolic extracts (13.27 and 15.09 mg/g, respectively). The extracts display high antioxidant activity with a 50% inhibition concentration (IC50) of 7.06 µg/ml for the ethanolic extract, 20.32 µg/ml for the aqueous extract and 6.69 µg/ml for ascorbic acid. Neither extract displayed toxicity by the method used (p> 0.05). Conclusions: It was found that the extracts do not display any toxicity, are capable of eliminating free radicals from the body and are a natural source of raw materials for drug manufacture.

Avaliação da atividade anti-Leishmania e anti-Trypanosoma do extrato etanólico das folhas de Annona squamosa L / Evaluation of the anti-leishmania and anti-trypanosoma activity of ethanolic extract from the leaves of Annona squamosa L

As doenças parasitárias, também chamadas de “doenças negligenciadas”, continuam sendo uma grande dificuldade para o desenvolvimento social e econômico dos países mais pobres. Podemos citar como exemplo dessas doenças, a leishmaniose e a doença de Chagas. A leishmaniose é causada por parasitas do gênero Leishmania e afeta cerca de 12 milhões de pessoas. A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, causa aproximadamente 50.000 mortes por ano. Os fármacos disponíveis para o tratamento dessas doenças são altamente tóxicos, sendo este um dos motivos que leva à busca por drogas eficazes e seguras para seus tratamentos. As folhas da Annona squamosa, espécie da família Annonaceae, já foram descritas na literatura por suas atividades hepatoprotetora, antiparasitária, pesticida e antimicrobiana. Nesse estudo avaliamos a atividade anti-leishmania e tripanocida do extrato etanólico das folhas de Annona squamosa L. (EEAS) em formas promastigota do parasita Leishmania braziliensis e Leishmania infantum e epimastigota de Trypanosoma cruzi, além de avaliar a atividade citotóxica em fibroblasto. Os resultados demonstram que o extrato apresentou uma melhor atividade contra Leishmania infantum e Leishmania brasiliensis quando comparados com Trypanosoma cruzi; e que apresentou uma maior toxicidade nas concentrações de 500 e 1000 μg/ml, com mortalidade dos fibroblastos de aproximadamente 85% e 100%, respectivamente. Esse estudo aponta para uma perspectiva terapêutica alternativa que se mostrou eficaz frente aos parasitas aqui estudados, exceto a forma epimastigota de Trypanosoma cruzi. Com relação aos testes de citotoxicidade fazem-se necessários novos testes, uma vez que apresentou um alto nível de toxicidade, viabilizando assim futuros ensaios in vivo.

The parasitic diseases, also calls by “neglected diseases”, continue being a major difficulty for the social and economic development of the poorest countries. We can cite as an example of these diseases, the leishmaniasis and the Chagas disease. Leishmaniasis is caused by parasites of the genus Leishmania and affects about 12 million people. The Chagas disease, caused by the protozoan Trypanosoma cruzi, causes approximately 50,000 deaths per year. The drugs available for the treatment of these diseases are highly toxic, being this one of the reasons that leads to the search for effective and safe drugs for their treatments. The leaves of the Annona squamosa, species of the family Annonaceae, have already been described in the literature by their hepatoprotective activities, antiparasitic, pesticide and antimicrobial. In this study we assessed the activity tripanocidal and antileishmania of ethanolic extract from the leaves of Annona squamosa L. (EEAS) in promastigota forms of the parasite Leishmania braziliensis and Leishmania infantum and epimastigota of Trypanosoma cruzi, in addition to evaluating the cytotoxic activity in fibroblasts. The results demonstrate that the extract presented a better activity against Leishmania infantum and Leishmania brasiliensis when compared with Trypanosoma cruzi; and which presented a greater toxicity at concentrations of 500 and 1000 μg/ml, with mortality of fibroblasts of approximately 85% and 100%, respectively. This study points to an alternative therapeutic perspective that showed effective against the parasites here studied, except the epimastigota form of Trypanosoma cruzi. With relation to cytotoxicity tests are required new tests, once presented a high level of toxicity, thus enabling future in vivo assays.

Avaliação da atividade antimicrobiana e moduladora do extrato etanólico de Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz / Evaluación de la actividad antimicrobiana y modulatória del extracto etanólico de Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz / Evaluation of antimicrobial and modulatory activity of the ethanol extract of Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz

Introdução: Staphylococcus aureus é mencionada na literatura como um importante patógeno, algumas espécimes acarretam infecções oportunistas em muitos animais e homens. Escherichia coli é uma das principais causas de doenças infecciosas humanas. Pertencente à família das Enterobacteriaceae, compartilham diversos fatores de virulência descrita por sua resistência a vários antibióticos, as contaminações são provavelmente iniciadas por modificações de defesas do hospedeiro. Pseudomonas aeruginosaé conhecida por causar infecção aguda pela produção de toxinas. Objetivo: avaliar o efeito antimicrobiano do extrato etanólico de Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz, e modulação da atividade antibiótica. Métodos: o material botânico de Libidibia ferrea foi coletado no município de Penaforte, Ceará, Brasil. Para a obtenção dos extratos foram coletadas entrecasca e vagem frescas, submersos em etanol separadamente por 72 h, sendo após esse período, filtrado e concentrado em condensador rotativo a vácuo. Foram realizados testes de atividade antimicrobiana e modulação da atividade antimicrobiana com cepas padrões e multirresistentes de bactérias. Resultados: o extrato demonstrou atividade moduladora quando combinados com alguns antimicrobianos contra algumas linhagens testadas. Conclusões: portanto, é sugerido que o extrato de L. ferrea pode ser utilizada como uma fonte de produtos naturais na terapêutica antimicrobiana e no combate a multirresistência bacteriana(AU)

Introducción: Staphylococcus aureus se menciona en la literatura como un patógeno importante, algunos provocan infecciones oportunistas en animales y hombres. Escherichia coli es una de las principales causas de enfermedades infecciosas humanas. Ambas pertenecen a la familia Enterobacteriaceae, comparten muchos factores de virulencia y se caracterizan por su resistencia a múltiples antibióticos, su contaminación tal vez iniciada por la modificación de las defensas del hospedero. Pseudomonas aeruginosa causa de infección aguda mediante la producción de toxinas. Objetivo: evaluar el efecto antimicrobiano del extracto de etanol de Libidibia ferrea (Mart ex Tul.) LP Queiroz, y la modulación de la actividad antibiótica. Métodos: L. ferrea fue recopilada en el municipio de Penaforte, Ceará, Brasil. Para obtener los extractos se recogieron corteza y frutos frescos, sumergidos en etanol por separado durante 72 h, después se filtraron y se concentraron en un condensador rotatorio. Se realizaron pruebas de actividad antimicrobiana y la modulación de la actividad antimicrobiana con cepas multirresistentes de bacterias. Resultados: los extractos mostraron actividad moduladora cuando se combina con algunos antibióticos contra algunas cepas ensayadas. Conclusión: por lo tanto, se sugiere que el extracto de L. ferrea puede ser utilizado como una fuente de productos naturales en la terapia antimicrobiana y en la resistencia a múltiples fármacos bacteriana combate(AU)

Introduction: Staphylococcus aureus is mentioned in the literature as an important pathogen, some opportunistic bacteria may cause several problems in many animals and humans. Escherichia coli is a leading cause of human infectious diseases. Belonging to the family Enterobacteriaceae, share many virulence factors described by their resistance to multiple antibiotics, the contamination is probably initiated by modifications in the host defenses. Pseudomonas aeruginosa is known to cause acute infection by producing toxins. Objective: evaluate the antimicrobial effect of the ethanol extract of Libidibia ferrea (Mart ex Tul.) LP Queiroz, and modulation of antibiotic activity. Methods: L. ferrea was collected in the municipality of Penaforte, Ceará, Brazil. To obtain the extracts were collected bark and fruits, submerged in ethanol separately for 72 h, after this period, filtered and concentrated in a rotary vacuum condenser. Antimicrobial activity tests were performed and modulation of antimicrobial activity with standards and multiresistant strains of bacteria. Results: the extract showed antibacterial activity when combined with some antibiotics against the assayed strains, demonstrating a modulatory potential. Conclusion: therefore, it is suggested that L. ferrea extract can be used as a source of natural products in the antimicrobial therapy and in the combat bacterial multidrug resistance(AU)

Avaliação da atividade antimicrobiana e moduladora do extrato hexânico de Costus cf. Arabicus L. / Evaluación de la actividad antimicrobiana y modulación del extracto de hexano de Costus cf. Arabicus L. / Evaluation of the antimicrobial and modulating activity of hexane extract from Costus cf. Arabicus L.

Introdução: a Pseudomonas aeruginosaé conhecida por causar infecção aguda pela produção de toxinas. Alguns espécimes deStaphylococcus são frequentemente reconhecidos como agentes etiológicos de infecções oportunistas em muitos animais e homens. Escherichia colié uma das principais causas de doenças infecciosas humanas. O gênero Candida produz diversos fatores de virulência, as infecções são provavelmente iniciadas por modificações de defesas do hospedeiro. Objetivo: avaliar o efeito antimicrobiano do extrato hexânico de Costus cf. e modulação da atividade antibiótica de Costus cf. Arabicus L. Métodos: o material botânico de Costus cf. Arabicus L., foi coletado no município de Crato, Ceará, Brasil. Para a preparação dos extratos foram coletados folhas e caules frescos, submersos em hexano separadamente por 72 h, sendo apósesse período, filtrado e concentrado em condensador rotativo a vácuo. Foram realizados testes de atividade antimicrobiana (CIM) e modulação da atividade antimicrobiana com cepas padrões e multirresistentes de bactérias e fungos. Resultados: o extrato demonstrou atividade antibacteriana e antifúngica quando combinados com alguns antimicrobianos contra algumas linhagens testadas. Conclusões: portanto, é sugerido que o extrato de Costus cf. pode ser utilizado como uma fonte de productos naturais na terapêutica antimicrobiana e no combate a multirresistência bacteriana e fúngica.

Introducción: Pseudomonas aeruginosa se ​​sabe que causa la infección aguda por la producción de toxinas. Algunos ejemplares de Staphylococcus suelen ser reconocidos como agentes etiológicos de las infecciones oportunistas en muchos animales y seres humanos. Escherichia coli es una de las principales causas de las enfermedades infecciosas humanas. El género Candida produce varios factores de virulencia, las infecciones son probablemente iniciadas por los cambios en las defensas del huésped. Objetivo: evaluar el efecto antimicrobiano del extracto de hexano de Costus cf. y la modulación de la actividad antibiótica de Costus cf. Arabicus L. Métodos: el material botánico de Costus cf. arabicus L. se recogió en Crato, Ceará, Brasil. Para la preparación de extractos se recogieron las hojas y los tallos frescos por separado y se sumergieron en hexano durante 72 horas, después de eso, se filtró y se concentró en un condensador de vacío rotatorio. Se realizaron ensayos de actividad antimicrobiana (MIC), modulación con cepas multirresistentes y patrones de bacterias y hongos. Resultados: el extracto mostró actividad antibacteriana y antifúngica cuando se combinan con algunos antibióticos contra algunas cepas ensayadas. Conclusiones: por lo tanto, el extracto de Costus cf. se puede utilizar como una fuente de productos naturales en la terapia antimicrobiana y en la lucha contra la resistencia a múltiples fármacos de bacterias y hongos.

Introduction: Pseudomonas aeruginosa is known to cause acute infection due to the production of toxins. Some specimens of Staphylococcus are often recognized as the etiologic agents of opportunistic infections in many animals and humans. Escherichia coli is a leading cause of human infectious diseases. The genus Candida produces several virulence factors. Infections are probably initiated by changes in host defenses. Objective: evaluate the antimicrobial effect of hexane extract of Costus cf. and themodulation of Costus cf. Arabicus. L. antibiotic activity. Methods: botanical material from Costus cf. arabicus L. was collected at Crato, Ceará, Brazil. For the preparation of extracts fresh leaves and stems were collected, separately immersed in hexane for 72 hours, and thereafter filtered and concentrated in a rotary vacuum condenser. Tests of antimicrobial activity (MIC) and antimicrobial activity modulation were conducted with multiresistant strain patterns of bacteria and fungi. Results: the extract showed antibacterial and antifungal activity against some of the strains tested when combined with some antibiotics. Conclusions: therefore, it is suggested that the extract of Costus cf. be used as a source of natural products for antimicrobial therapy and to combat bacterial and fungal multidrug resistance.