RESUMEN
This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.
Asunto(s)
Antibacterianos , Antifúngicos , Venenos de Crotálidos , Crotalus , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Antibacterianos/farmacología , Venenos de Crotálidos/farmacología , Animales , Staphylococcus aureus/efectos de los fármacos , Sinergismo Farmacológico , Candida albicans/efectos de los fármacos , Serpientes VenenosasRESUMEN
Fungal infections are a public health problem that mainly affects immunosuppressed people, Candida spp. have been responsible for most sources of contamination and invasive fungal infections described around the world. The need arises to find new therapeutic approaches to combat growing infections. Plants and natural products have been considered a valuable source for discovering new molecules with active ingredients. Diosgenin is a sapogenin found in the families of Leguminosae and Dioscoreaceae, it is obtained mainly from the dioscin saponin through the hydrolysis method, it is a phytochemical that has been highlighted in the treatment of various diseases, as well as in combating microbial resistance. The present study aimed to evaluate the susceptibility of fungal strains to diosgenin, as well as verify the association with the reference drug and evaluate the inhibition of the virulence factor through morphological changes in the yeast state to the filamentous form of hyphae and pseudohyphae in strains of Candida albicans, Candida tropicalis and Candida krusei using the broth microdilution method and microculture technique. Antifungal assays revealed that diosgenin was not able to inhibit the growth of the tested strains. However, it was able to inhibit the fungal dimorphism of the strains evaluated, however further studies are recommended to verify its effectiveness against other virulence factors.
Asunto(s)
Antifúngicos , Candida , Diosgenina , Pruebas de Sensibilidad Microbiana , Diosgenina/farmacología , Diosgenina/química , Diosgenina/análogos & derivados , Antifúngicos/farmacología , Antifúngicos/química , Candida/efectos de los fármacos , Virulencia/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidadRESUMEN
The increased resistance of microorganisms to antimicrobial drugs makes it necessary to search for new active compounds, such as chalcones. Their simple chemical structure makes them molecules easy to synthesize. Therefore, the aim of this study was to evaluate the antimicrobial and potentiating activity of antibiotics and antifungals by synthetic chalcones against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. The synthesis of chalcones was carried out by Claisen-Schimidt aldol condensation. Nuclear Magnetic Resonance (NMR) and Gas Chromatography Coupled to Mass Spectrometry (GC/MS) were also performed. Microbiological tests were performed by the broth microdilution method, using gentamicin, norfloxacin and penicillin as standard drugs for the antibacterial assay, and fluconazole for the antifungal assay. Three chalcones were obtained (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnone-1,3,6,8-tetraen-5-one (DB-CNM), (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB-Anisal). The compound DB-Acetone was able to inhibit P. aeruginosa ATCC 9027 at a concentration of 1.4 × 102 µM (32 µg/mL), while DB-CNM and DB-Anisal inhibited the growth of S. aureus ATCC 25923 at 17.88 × 102 µM and 2.71 × 101 µM (512 µg/mL and 8 µg/mL) respectively. In the combined activity, DB-Anisal was able to potentiate the effect of the three antibacterial drugs tested against E. coli 06, norfloxacin (128 for 4 µg/mL ±1) against P. aeruginosa 24 and penicillin (1,024 for 16 µg/mL ±1) against S. aureus 10. In antifungal assays, chalcones were not able to inhibit the growth of fungal strains tested. However, both showed potentiating activity with fluconazole, ranging from 8.17 x 10-1 µM (0.4909 µg/mL) to 2.35 µM (13.96 µg/mL). It is concluded that synthetic chalcones have antimicrobial potential, demonstrating good intrinsic activity against fungi and bacteria, in addition to potentiating the antibiotics and antifungal tested. Further studies are needed addressing the mechanisms of action responsible for the results found in this work.
Asunto(s)
Antiinfecciosos , Chalconas , Antifúngicos/química , Fluconazol/farmacología , Chalconas/farmacología , Chalconas/química , Staphylococcus aureus , Norfloxacino/farmacología , Escherichia coli , Acetona/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/química , Candida albicans , Penicilinas/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Lectins participate in the defense against microorganisms and in signaling the damage caused by pathogens to the cell surface and/or intracellular in plants. This study aims to analyze the antifungal potential of lectins extracted from seeds of Canavalia ensiformis (L.) DC and Canavalia rosea (Sw.) DC, against Candida albicans and Candida tropicalis. The antimicrobial tests were performed by microdilution against Candida spp. The test to verify the combined lectin/fluconazole effect was performed using subinhibitory concentrations of lectins and with antifungal ranging from 0.5 to 512 µg/mL. The ability to inhibit the morphological transition of Candida spp. was evaluated by microcultivation in a moist chamber. The results of the minimum inhibitory concentration revealed no antifungal activity against the tested strains. However, lectins modified the action of fluconazole, reducing the IC50 of the drug against C. albicans. Lectins were also able to discretely modulate the morphological transition of the tested strains.
Asunto(s)
Candida albicans , Candida tropicalis , Antifúngicos/farmacología , Canavalia/metabolismo , Candida/metabolismo , Concanavalina A , Fluconazol/farmacología , Lectinas/farmacología , Pruebas de Sensibilidad Microbiana , PlanctonRESUMEN
Weeds are an important source of natural products; with promising biological activity. This study investigated the anti-kinetoplastida potential (in vitro) to evaluate the cytotoxicity (in vitro) and antioxidant capacity of the essential oil of Rhaphiodon echinus (EORe), which is an infesting plant species. The essential oil was analyzed by GC/MS. The antioxidant capacity was evaluated by reduction of the DPPH radical and Fe3+ ion. The clone Trypanosoma cruzi CL-B5 was used to search for anti-epimastigote activity. Antileishmanial activity was determined using promastigotes of Leishmania braziliensis (MHOM/CW/88/UA301). NCTC 929 fibroblasts were used for the cytotoxicity test. The results showed that the main constituent of the essential oil was γ-elemene. No relevant effect was observed concerning the ability to reduce the DPPH radical; only at the concentration of 480 µg/mL did the essential oil demonstrate a high reduction of Fe3+ power. The oil was active against L. brasiliensis promastigotes; but not against the epimastigote form of T. cruzi. Cytotoxicity for mammalian cells was low at the active concentration capable of killing more than 70% of promastigote forms. The results revealed that the essential oil of R. echinus showed activity against L. brasiliensis; positioning itself as a promising agent for antileishmanial therapies.
Asunto(s)
Antiprotozoarios , Enfermedad de Chagas , Lamiaceae , Leishmaniasis Mucocutánea , Aceites Volátiles , Trypanosoma cruzi , Animales , Antioxidantes/farmacología , Antiprotozoarios/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Mamíferos , Aceites Volátiles/farmacologíaRESUMEN
This study aimed to identify the chemical composition of the Spondias tuberosa aqueous leaf and root extracts (EALST and EARST) and to evaluate their effect, comparatively, against opportunistic pathogenic fungi. Ultra-Performance Liquid Chromatography Coupled to a Quadrupole/Time of Flight System (UPLC-MS-ESI-QTOF) was employed for chemical analysis. Candida albicans and C. tropicalis standard strains and clinical isolates were used (CA INCQS 40006, CT INCQS 40042, CA URM 5974, and CT URM 4262). The 50% Inhibitory Concentration for the fungal population (IC50) was determined for both the intrinsic action of the extracts and the extract/fluconazole (FCZ) associations. The determination of the Minimum Fungicidal Concentration (MFC) and the verification of effects over fungal morphological transitions were performed by subculture in Petri dishes and humid chambers, respectively, both based on micro-dilution. UPLC-MS-ESI-QTOF analysis revealed the presence of phenolic and flavonoid compounds. The association of the extracts with fluconazole, resulted in IC50 values from 2.62 µg/mL to 308.96 µg/mL. The MFC of the extracts was ≥16,384 µg/mL for all tested strains, while fluconazole obtained an MFC of 8192 µg/mL against C. albicans strains. A reduction in MFC against CA URM 5974 (EALST: 2048 µg/mL and EARST: 1024 µg/mL) occurred in the extract/fluconazole association.
Asunto(s)
Antifúngicos , Fluconazol , Antifúngicos/química , Fluconazol/farmacología , Cromatografía Liquida , Cromatografía Líquida de Alta Presión , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Candida albicans , Candida tropicalis , Pruebas de Sensibilidad MicrobianaRESUMEN
One of the main global problems that affect human health is the development of bacterial resistance to different drugs. As a result, the growing number of multidrug-resistant pathogens has contributed to an increase in resistant infections and represents a public health problem. The present work seeks to investigate the chemical composition and antibacterial activity of the essential oil of Syzygium cumini leaves. To identify its chemical composition, gas chromatography coupled to mass spectrometry was used. The antibacterial activity test was performed with the standard strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 25853 and Staphylococcus aureus ATCC 25923 and multidrug-resistant clinical isolates E. coli 06, P. aeruginosa 24 and S. aureus 10. The minimum inhibitory concentration (MIC) was determined by serial microdilution as well as the verification of the modulating effect of the antibiotic effect. In this test, the oil was used in a subinhibitory concentration. The test reading was performed after 24 h of incubation at 37 °C. The results show that the major chemical constituent is α-pinene (53.21%). The oil showed moderate activity against E. coli ATCC 25922, with the MIC of 512 µg/mL; there was no activity against the other strains. The oil potentiated the effect of antibiotics demonstrating possible synergism when associated with gentamicin, erythromycin and norfloxacin against E. coli 06 and S. aureus 10.
Asunto(s)
Aceites Volátiles , Syzygium , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli , Cromatografía de Gases y Espectrometría de Masas , Humanos , Aceites Volátiles/química , Aceites Volátiles/farmacología , Fitoquímicos/farmacología , Pseudomonas aeruginosa , Staphylococcus aureusRESUMEN
Species of the genus Miconia are used in traditional medicine for the treatment of diseases, such as pain, throat infections, fever, and cold, and they used as depuratives, diuretics, and sedatives. This work reviewed studies carried out with Miconia species, highlighting its ethnomedicinal uses and pharmacological and phytochemical potential. This information was collected in the main platforms of scientific research (PubMed, Scopus, and Web of Science). Our findings show that some of the traditional uses of Miconia are corroborated by biological and/or pharmacological assays, which demonstrated, among other properties, anti-inflammatory, analgesic, antimutagenic, antiparasitic, antioxidant, cytotoxic, and antimicrobial activities. A total of 148 chemical compounds were identified in Miconia species, with phenolic compounds being the main constituents found in the species of this genus. Such phytochemical investigations have demonstrated the potential of species belonging to this genus as a source of bioactive substances, thus reinforcing their medicinal and pharmacological importance.
Asunto(s)
Melastomataceae , Etnofarmacología , Medicina Tradicional , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
This study aimed to investigate the chemical composition and antifungal potential of the essential oil of Baccharis trimera (Less.) DC. against Candida strains. The half maximal inhibitory concentration (IC50) was assessed by the microdilution method using the essential oil at a concentration range of 8192 to 8 µg/mL. The minimum fungicide concentration (MFC) was determined by subculture in solid medium. The ability of the essential oil to modulate the activity of antifungals was determined in wells treated simultaneously with the oil at a subinhibitory concentration (MFC/16) and fluconazole (FCZ). The fungal morphology was analyzed by microscopy. Gas chromatography coupled with mass spectrometry (GC/MS) was used to identify the chemical composition. The essential oil presented an CI50 of 11.24 and 1.45 µg/mL, which was found to potentiate the effect of FCZ against Candida albicans. On the other hand, this combined treatment resulted in antagonism against Candida tropicalis and no evident modulation against Candida krusei was observed. The essential oil significantly inhibited hyphae growth. However, with a MFC ≥ 16,384 µg/mL, it is assumed that it has a fungistatic action. The antifungal properties demonstrated in this study might be related to the presence of sesquiterpenes and monoterpenes, and the interaction between them. In conclusion, Baccharis trimera showed promising anti-Candida effects, in addition to potentiating the activity of FCZ against Candida albicans, affecting its morphological transition. Therefore, this species constitutes a source of chemical compounds with the potential to be used in the combat of fungal infections.
Asunto(s)
Baccharis , Candida , Aceites Volátiles , Antifúngicos/farmacología , Baccharis/química , Candida/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Fitoquímicos/farmacología , Pichia/efectos de los fármacosRESUMEN
Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties.
RESUMEN
The genus Echinacea consists of 11 taxa of herbaceous and perennial flowering plants. In particular, Echinacea purpurea (L.) Moench is widely cultivated all over the United States, Canada, and in Europe, exclusively in Germany, for its beauty and reported medicinal properties. Echinacea extracts have been used traditionally as wound healing to improve the immune system and to treat respiratory symptoms caused by bacterial infections. Echinacea extracts have demonstrated antioxidant and antimicrobial activities, and to be safe. This survey aims at reviewing the medicinal properties of Echinacea species, their cultivation, chemical composition, and the potential uses of these plants as antioxidant and antibacterial agents in foods and in a clinical context. Moreover, the factors affecting the chemical composition of Echinacea spp. are also covered.
Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Echinacea/química , Extractos Vegetales/farmacología , Conservantes de Alimentos/farmacología , Humanos , Medicina Tradicional , Aceites Volátiles/química , Fitoterapia , Plantas Medicinales/químicaRESUMEN
Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties on the basis of their use in folk medicine. Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders, as well as muscular pain, across the world. Furthermore, these plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The phytochemical composition of the extracts of different Tagetes species parts are reported in this work. These compounds exhibit antioxidant, antiinflammatory, and enzyme inhibitory properties. Cultivation and the factors affecting the chemical composition of Tagetes species are also covered. In the current work, available literature on Tagetes species in traditional medicine, their application as a food preservative, and their antimicrobial activities are reviewed.
Asunto(s)
Aceites Volátiles/química , Aceites Volátiles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Tagetes/química , Agricultura , Antiinfecciosos/química , Antiinfecciosos/farmacología , Aditivos Alimentarios , Conservantes de Alimentos , Medicina Tradicional , Fitoquímicos/química , Fitoquímicos/farmacologíaRESUMEN
The association of herbal products with standard antimicrobial drugs has recently gained more attention as a hope to overcome infectious diseases caused by multidrug-resistant microorganisms. Here, we investigated for the first time the antimicrobial (antifungal and antibacterial) activity of ethanolic and aqueous extracts of R. echinus against multiresistant strains of bacteria (E. coli, P. aeruginosa and S. aureus) and fungi (C. albicans, C. krusei and C. tropicalis), as well as potential to enhance the activity of antibiotics drugs. In addition, both extract were chemically characterized and their toxicity was assessed in Artemia salina. Our results demonstrate that aqueous extract of R. echinus caused a significant increase in the activity of antibiotics gentamicin and imipenem, while the ethanolic extract strongly enhanced the antibiotic activity of gentamicin, amikacin, imipenem and ciprofloxacin against P. aeruginosa. However, neither the ethanolic nor the aqueous extracts significantly affect the antibiotic activity of the drugs when tested against S. aureus. Phytochemical analysis of the extracts indicated ellagic acid, caffeic acid and chlorogenic acid as the major components which can be at least in part responsible for the enhanced activity of antibiotics. None of the extracts showed toxicity in A. salina even at the highest concentration tested (1000 µg/mL). All together, our results suggest that the leaf extract of R. echinus can be an effective source of modulating agents.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Extractos Vegetales/farmacología , Tracheophyta/química , Animales , Antibacterianos/química , Antifúngicos/química , Artemia/efectos de los fármacos , Bacterias/efectos de los fármacos , Candida/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Hojas de la Planta/química , Pseudomonas aeruginosa/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacosRESUMEN
Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against Leishmania braziliensis and Trypanosoma cruzi. The results demonstrated that L. camara essential oil inhibited T. cruzi and L. braziliensis with IC50 of 201.94 µg/mL and 72.31 µg/mL, respectively. L. camara essential oil was found to be toxic to NCTC929 fibroblasts at 500 µg/mL (IC50 = 301.42 µg/mL). The composition of L. camara essential oil analyzed by gas chromatography-mass spectrometry (GC/MS) revealed large amounts of (E)-caryophyllene (23.75%), biciclogermacrene (15.80%), germacrene D (11.73%), terpinolene (6.1%), and sabinene (5.92%), which might be, at least in part, responsible for its activity. Taken together, our results suggest that L. camara essential oil may be an important source of therapeutic agents for the development of alternative drugs against parasitic diseases.
Asunto(s)
Lantana/química , Leishmania/efectos de los fármacos , Aceites Volátiles/análisis , Aceites Volátiles/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citostáticos/análisis , Citostáticos/química , Citostáticos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Ratones , Aceites Volátiles/química , Hojas de la Planta/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa Gomes is a fruit and medicinal species used for treating infectious diseases of the genitourinary system. However, its mechanism of action against microbes is still not fully understood. Infections in the genitourinary system caused by Candida spp. are associated with its fungal resistance and pathogenicity. New plant-derived compounds are an alternative to fight these Candida infections. AIM OF THE STUDY: The objective of this study was to evaluate the anti-Candida effects of extracts of the stem bark of H. speciosa. This research investigated the chemical composition of sulfuric ether (EEHS) and methanolic (MEHS) extracts, their drug-modifying action on fluconazole, and their anti-virulence action on the morphological transition of Candida species. MATERIALS AND METHODS: The extracts (EEHS and MEHS) of the stem bark of H. speciosa were chemically characterized via qualitative phytochemical screening and by liquid chromatography coupled with mass spectrometry (UPLC-MS-ESI-QTOF). The extracts were evaluated regarding their antifungal effects and fluconazole-modifying activity against Candida albicans, Candida krusei, and Candida tropicalis using the broth microdilution method. Additionally, the study evaluated the inhibition of fungal virulence in Candida species through morphological transition assays. RESULTS: The phytochemical screening revealed the presence of anthocyanidins, anthocyanins, aurones, catechins, chalcones, flavones, flavonols, flavanones, leucoanthocyanidins, tannins (condensed and pyrogallic), and xanthones in both extracts of the stem bark of H. speciosa. The UPLC-MS-ESI-QTOF analysis identified the same compounds in both extracts, predominating phenolic compounds. Some compounds were first time recorded in this species: gluconic acid, cinchonain IIb, cinchonain Ib isomer, and lariciresinol hexoside isomers. Most of the intrinsic antifungal activity was observed for the MEHS against C. krusei (IC50: 58.41 µg/mL). At subinhibitory concentrations (MC/8), the EEHS enhanced the action of fluconazole against all Candida strains. The MEHS exhibited greater efficacy than fluconazole inhibiting C. krusei growth. The EEHS completely inhibited hyphae appearance and reduced pseudohyphae formation in C. albicans. CONCLUSION: The stem bark of H. speciosa is a rich source of bioactive compounds, especially phenolic. Phenolic compounds can have important roles in fighting infectious diseases of the genitourinary system, such as candidiasis. The extracts of H. speciosa improved the action of the drug fluconazole against Candida species, inhibited hyphae appearance, and reduced pseudohyphae formation. The results of this study can support the development of new therapeutics against resistant strains of Candida.
Asunto(s)
Apocynaceae , Candidiasis , Enfermedades Transmisibles , Antifúngicos/farmacología , Antifúngicos/química , Candida , Fluconazol/farmacología , Virulencia , Cromatografía Liquida , Apocynaceae/química , Corteza de la Planta/química , Antocianinas/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectrometría de Masas en Tándem , Candida albicans , Fitoquímicos/análisis , Pruebas de Sensibilidad MicrobianaRESUMEN
The present article aims to evaluate the antifungal and antivirulence effect of the phytoconstituent Limonene against Candida spp. Antifungal assays were performed, where the concentration capable of inhibiting 50 % of fungal growth, the growth inhibition curve, the minimum fungicidal concentration, the evaluation of the modifying effect with fluconazole, the inhibitory effect of the substances on the morphological transition of Candida spp. and the statistical analysis of the results were determined. With this study, it was seen that limonene demonstrated growth inhibition for the strains tested and when associated the natural compound with Fluconazole, there was potentiation of the effect of the drug, since the inhibition of growth by the combination occurred at lower concentrations against all strains tested, when compared to the drug alone, which inhibited growth at the highest concentration. In the test to determine the Minimum Fungicidal Concentration of the products tested alone and in combination, it was found that in the case of Candida strains, growth inhibition by limonene occurred at a concentration of 1024 µg/mL. For Fluconazole, growth impairment ranged from > 1024 µg/mL to 256 µg/mL for the strains. And when combined, limonene potentiated the action of FCZ, making fungal colonization unfeasible at concentrations below 1024 µg/mL. Regarding the morphological transition from yeast to hyphae, limonene was used at concentrations of 1024 µg/mL and 512 µg/mL, and it was found that, for CA and CK, the filaments were reduced in number and size at the highest concentration and against CT, the morphological transition from yeast to hyphae/pseudohyphae was totally inhibited, and if compared to the growth control, limonene was able to reduce fungal growth at concentrations greater than 512 µg/mL. This compound has antimicrobial activity described, due to its ability to interfere in the gene expression of the fungus, the limited therapeutic options and the recent emergence of multidrug-resistant Candida species represent a significant challenge for human medicine and highlight the need for new therapeutic approaches, and in this study a great potential of limonene was revealed in relation to the perspective of increasing the efficiency of commercial drug. This work can bring an important contribution to the scientific database, while emphasizing that in-depth studies and tests on the subject, in order to better investigate its effectiveness and mechanisms by which they exert their effects, are still necessary.
Asunto(s)
Antifúngicos , Candida , Humanos , Antifúngicos/farmacología , Fluconazol/farmacología , Limoneno/farmacología , Saccharomyces cerevisiae , Virulencia , Hongos , Pruebas de Sensibilidad MicrobianaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa is a medicinal plant popularly used to treat different medical issues, including infectious diseases. Exploring the therapeutic potentialities of the extracts from medicinal plants combined with conventional antibiotic drugs is a promising horizon, especially considering the rising microbial resistance. AIM OF THE STUDY: This study aimed to characterize the chemical composition of the ethereal (EEHS) and methanolic (MEHS) extracts of the stem bark of H. speciosa, and also evaluate their antibacterial and drug-modifying activity, and toxicity. MATERIALS AND METHODS: The extracts were characterized by gas chromatography coupled to mass spectrometry (GC-MS). Additionally, total phenol and flavonoid contents were determined. The antibacterial and antibiotic-modifying activity was evaluated against strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa using the serial microdilution method, obtaining the minimum inhibitory concentration (MIC). The toxicity assay was carried out using the Drosophila melanogaster model. RESULTS: Thirty compounds were identified in the extracts of the stem bark of H. speciosa, with triterpenoids being predominant in both extracts. Additionally, fatty alcohols, carbohydrates, fatty acids, phenolic acids, and phytosterols were identified in both extracts. EEHS and MEHS extracts had considerable phenol contents (346.4 and 340.0 mg GAE/g, respectively). Flavonoids were detected in a lower proportion (7.6 and 6.9 mg QE/g, respectively). H. speciosa extracts did not display intrinsic antibacterial activity against the bacterial strains evaluated, however, they were capable of modifying the activity of gentamicin, erythromycin, and norfloxacin. EEHS increased the efficacy of norfloxacin against E. coli and S. aureus, reducing MIC values by 50%. MEHS potentiated the action of gentamicin against all bacterial strains, especially against E. coli. The extracts did not display toxicity at clinically relevant concentrations against D. melanogaster. CONCLUSION: The stem bark of H. speciosa was considered a rich source of bioactive compounds. Our findings evidenced the therapeutic potential of H. speciosa extracts for the development of new pharmaceutical therapeutics against bacteria. Although the extracts did not exhibit intrinsic antibacterial activity, they enhanced the efficacy of commercial antibiotic drugs and were non-toxic at clinically relevant concentrations. Future studies are needed to elucidate the mechanisms of action of these extracts, ensuring their safety and efficacy.
RESUMEN
Cordiera myrciifolia is an abundant species in Northeast Brazil that presents metabolites of biological/therapeutic interest. From this perspective, the present study aimed to investigate the chemical constituents and evaluate the in vitro antimicrobial activity of hexane (HECM) and ethanolic (EECM) extracts of C. myrciifolia leaves. The extracts were analyzed by chromatographic techniques (GC and UPLC) coupled with mass spectrometry. The antimicrobial activity of the extracts and the extracts combined with conventional drugs was evaluated by microdilution. The in vitro effect of the treatments on Candida's morphological transition was verified through cultivation in humid chambers. In HECM, 11 constituents including fatty acids, and triterpenes, including phytosterols, alkanes, tocols, and primary alcohols were identified. Triterpenes represented >40% of the identified constituents, with Lupeol being the most representative. In EECM, 13 constituents were identified, of which eight belonged to the class of flavonoids. High antibacterial activity of HECM was detected against Escherichia coli and Staphylococcus aureus, with Minimum Inhibitory Concentrations of 8 and 16 µg/mL, respectively. The combined activity was more effective when combined with Norfloxacin and Imipenem. In anti-Candida activity, the IC50 of the extracts ranged from 36.6 to 129.1 µg/mL. There was potentiating effect when associated with Fluconazole. Both extracts inhibited the filamentous growth of C. tropicalis at a concentration of 512 µg/mL. C. myrciifolia extracts prove to be candidates for the development of new therapeutic formulations to treat bacterial and fungal infections.
Asunto(s)
Antiinfecciosos , Bacterias , Hongos , Extractos Vegetales , Rubiaceae , Hojas de la Planta/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Rubiaceae/química , Concentración 50 Inhibidora , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacologíaRESUMEN
Fungi of the Candida genus are responsible for invasive candidiasis, which affects people all over the world and has high mortality rates. This is due to their virulence factors, which give them great resistance and pathogenicity. In addition, the emergence of multidrug-resistant strains makes it difficult to treat these infections. In this way, natural products have emerged as an alternative to standard drugs, where plants known for their medicinal properties such as Turnera subulata become attractive to research. The present work aimed to analyze the ethanol extract of Turnera subulata leaves against standard strains of Candida albicans, Candida krusei and Candida tropicalis using broth microdilution techniques. The identification of the compounds in T. subulata leaves by LC-MS revealed the presence of a wide variety of substances such as carboxylic acids and terpenes, with flavonoids and fatty acids being more evident. The antifungal assays showed that the extract was not able to inhibit the growth of the tested strains at concentrations with a clinical relevance. However, at higher concentrations, it was able to inhibit the fungal dimorphism of C. albicans and C. tropicalis. It is possible that the T. subulata extract has potential as an inhibitor of fungal virulence factors without affecting the cell viability. Further research should be carried out in order to assess its inhibitory potential for other fungal virulence factors.
RESUMEN
Lectins are biologically versatile biomolecules with remarkable antimicrobial effects, notably against bacteria, fungi and protozoa, in addition to modulating host immunity. For this, the lectins bind to carbohydrates on the surface of the pathogen, which can cause damage to the cell wall and prevent the attachment of microorganisms to host cells. Thus, this study intends to review the biological activities of lectins, with an emphasis on antimicrobial activity. Lectins of plant stood out for its antimicrobial effects, demonstrating that they act against a variety of strains, where in vitro were able to inhibit their development and affect their morphology. In vivo, they modulated host immunity, signaling and activating defense cells. Some of these lectins were capable to modulate the action of antibiotics, indicating their potential to minimize the antibiotic resistance. The results suggest that lectins have antimicrobial activity with potential to be used in drug development.