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Fungi are becoming increasingly resistant, especially the new strains. Therefore, this work developed nanoemulsions (NE) containing micafungin (MICA), in order to improve its action against infections caused by Candida auris. The NEs were composed of the surfactants polyoxyethylene (20) cetyl ether (Brij 58®)/soy phosphatidylcholine at 10%, sunflower oil/cholesterol at 10%, and 80% PBS. The NEs were characterized by Dynamic Light Scattering (DLS). For the microbiological in vitro evaluation the determination of the minimum inhibitory concentration (MIC), ergosterol/sorbitol, time kill and biofilms tests were performed. Additionally, the antifungal activity was also evaluated in a Galleria mellonella model. The same model was used in order to evaluate acute toxicity. The NE showed a size of â¼ 42.12 nm, a polydispersion index (PDI) of 0.289, and a zeta potential (ZP) of -3.86 mV. NEM had an average size of 41.29 nm, a PDI of 0.259, and a ZP of -4.71 mV. Finally, both nanoemulsions showed good stability in a storage period of 3 months. Although NEM did not show activity in planktonic cells, it exhibited action against biofilm and in the in vivo infection model. In the alternative in vivo model assay, it was possible to observe that both, NEM and free MICA at 0.2 mg/l, was effective against the infection, being that NEM presented a better action. Finally, NEM and free MICA showed no acute toxicity up to 4 mg/l. NEM showed the best activities in in vitro in mature antibiofilm and in alternative in vivo models in G. mellonella. Although, NEs showed to be attractive for MICA transport in the treatment of infections caused by C. auris in vitro and in vivo studies with G. mellonella, further studies should be carried out, in mice, for example.
Candida auris is a fungus that can cause infections in the human body. As it is a microorganism with a high potential for resistance, it is extremely important to develop new therapeutic alternatives. Thus, nanotechnology, the science that studies materials with extremely small sizes, can be considered a promising method in the treatment of these infections.
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Antifúngicos , Ergosterol , Animales , Ratones , Micafungina/farmacología , Antifúngicos/farmacología , Pruebas de Sensibilidad Microbiana/veterinaria , BiopelículasRESUMEN
The rate of infections caused by resistant bacteria to the antimicrobials available for human use grows exponentially every year, which generates major impacts on human health and the world economy. In the last two decades, human beings can witness the expressive increase in the Science and Technology worldwide, and areas such as Health Sciences have benefited from these advances in favor of human health, such as the advent of Pharmaceutical Nanotechnology as an important approach applied for bacterial infections treatment with resistance profile to available antibiotics. This review of the scientific literature brings the applicability of nanotechnology-based lipid systems as an innovative tool in the improvement of bacterial infections treatment. Important studies involving the use of liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, microemulsions and lipid nanocapsules were verified in the period from 2000 to 2020, where important scientific results were found and will serve as a basis for the use of these systems to remain in constant updating. This manuscript shows the use of these drug delivery systems as potential vehicles for antibacterial compounds, which opens a new hope in the complement of the antibacterial therapeutic arsenal. Important studies developed in the last 20 years are present in this review, and thus guarantees an update on the use of these drug delivery systems for researchers from different areas of Health Sciences.
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Sistemas de Liberación de Medicamentos , Nanopartículas , Bacterias , Portadores de Fármacos , Humanos , Lípidos , NanotecnologíaRESUMEN
Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases of invasive fungal infections. The use of this drug is widely appreciated in the medical field due to be the most active echinocandin available for invasive fungal infections. In order to provide important parameters related to the chemical, physical, biological and therapeutic characteristics, this review article gathers important research results that demonstrate the biological potential of this drug, as well as to present analytical methods that can be used to determine the antifungal potential and a monitoring of administered dosages. Important studies about the methods most commonly used in biological activity evaluation and determination/quantification by analytical methods are provided in this review article. With the data provided, the scientific community will have the possibility to choose the analytical methods and biological that can be employed in clinical and scientific research to provide greater safety and reliability of the results to be found.
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Antifúngicos/análisis , Antifúngicos/metabolismo , Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Micafungina/análisis , Micafungina/metabolismo , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Aspergillus fumigatus/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Farmacorresistencia Fúngica , Equinocandinas/farmacología , Electroforesis Capilar , Humanos , Micafungina/administración & dosificación , Micafungina/efectos adversos , Solubilidad , Espectrometría de Masas en Tándem , Resultado del TratamientoRESUMEN
Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.
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Systemic infections is one of the major causes of mortality worldwide, and a shortage of drug approaches applied for the rapid and necessary treatment contribute to increase the levels of death in affected patients. Several drug delivery systems based in nanotechnology such as metallic nanoparticles, liposomes, nanoemulsion, microemulsion, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, hydrogels and liquid crystals can contribute in the biological performance of active substances for the treatment of microbial diseases triggered by fungi, bacteria, virus and parasites. In the presentation of these statements, this review article present and demonstrate the effectiveness of these drug delivery systems for the treatment of systemic diseases caused by several microorganisms, through a review of studies on scientific literature worldwide that contributes to better information for the most diverse professionals from the areas of health sciences. The studies demonstrated that the drug delivery systems described can contribute to the therapeutic scenario of these diseases, being classified as safe, active platforms and with therapeutic versatility.
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Nanopartículas , Nanotecnología , Sistemas de Liberación de Medicamentos , Humanos , Lípidos , Liposomas , PolímerosRESUMEN
The crescent number of cases of candidiasis and the increase in the number of infections developed by non-albicans species and by multi-resistant strains has taken the attention of the scientific community, which has been searching for new therapeutic alternatives. Among the alternatives found the use of nanosystems for delivery of drugs already commercialized and new biomolecules have grown, in order to increase stability, solubility, optimize efficiency and reduce adverse effects. In view of the growing number of studies involving technological alternatives for the treatment of candidiasis, the present review came with the intention of gathering studies from the last two decades that used nanotechnology for the treatment of candidiasis, as well as analysing them critically and pointing out the future perspectives for their application with this purpose. Different studies were considered for the development of this review, addressing nanosystems such as metallic nanoparticles, mesoporous silica nanoparticles, polymeric nanoparticles, liposomes, nanoemulsion, microemulsion, solid lipid nanoparticle, nanostructured lipid carrier, lipidic nanocapsules and liquid crystals; and different clinical presentations of candidiasis. As a general overview, nanotechnology has proven to be an important ally for the treatment against the diversity of candidiasis found in the clinic, whether in increasing the effectiveness of commercialized drugs and reducing their adverse effects, as well as allowing exploring more effectively properties therapeutics of new biomolecules.
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Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Nanopartículas/uso terapéutico , Animales , Antifúngicos/química , Antifúngicos/historia , Candidiasis/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Nanopartículas/química , Nanopartículas/historia , Nanotecnología/historiaRESUMEN
PURPOSE: Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection that adversely affects a woman's health, due to unpleasant symptoms, therapeutic challenges, and the emergence of resistant strains. The association of natural products and nanotechnology is important to improve the antifungal potential of medicinal plants. We aimed to evaluate the in vitro and in vivo anti-Candida albicans activity of unloaded (EO) and loaded (ME+EO) essential oil of Cymbopogon nardus in the microemulsion (ME). METHODS: The chemical analysis of the EO was performed by gas chromatography-mass spectrometry. The ME and ME+EO were characterized by scattering, zeta potential, polarized light microscopy, rheological assays, mucoadhesiveness and transmission electronic microscopy. The in vitro antifungal activity of the EO and ME+EO were evaluated by microdilution technique. The toxicity of EO and ME+EO was analyzed on human cell line HaCat and using alternative model assay with Artemia salina. The experimental in vivo VVC was performed in female mice (C57BL/6). RESULTS: The main compounds of the EO were found to be citronellal, geranial, geraniol, citronellol, and neral. The formulations exhibited suitable size, homogeneity, negative charge, isotropic behavior, highly organized structure, and pseudoplastic behavior, for vaginal application. TEM photomicrographs showed possible EO droplets inside the spherical structures. The EO, when loaded into the ME, exhibited an improvement in its antifungal action against C. albicans. The EO was not toxic against brine shrimp nauplii. An in vivo VVC assay showed that the use of the ME significantly improved the action of the EO, since only the ME+EO promoted the eradication of the fungal vaginal infection on the third day of treatment. CONCLUSION: The EO and ME+EO are promising alternatives for the control of fungal infections caused by C. albicans, once the use of nanotechnology significantly improved the antifungal action of the EO, especially in an in vivo model of VVC.
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Candida albicans/efectos de los fármacos , Cymbopogon/química , Emulsiones/química , Aceites Volátiles/farmacología , Anfotericina B/farmacología , Animales , Antifúngicos/farmacología , Artemia/efectos de los fármacos , Ergosterol/farmacología , Femenino , Células HaCaT , Humanos , Concentración 50 Inhibidora , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Reología , Electricidad Estática , Pruebas de ToxicidadRESUMEN
We have previously reported on the activity of different extracts from Astronium sp. against Candida albicans, with the hydroethanolic extract prepared from leaves of A. urundeuva, an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest in vitro activity. Here we have further evaluated the antifungal activity of this extract against strains of C. albicans and C. glabrata, the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407®). In vitro susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both Candida species, with increased activity against C. glabrata, including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against C. albicans. Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by C. albicans at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using Artemia salina L. confirmed a good safety profile of the both free and loaded extracts, and an in vivo assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the A. urundeuva leaves extract to be further investigated and developed as an antifungal.
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In this study, was evaluated the chemical composition of a fraction from Syngonanthus nitens extract and its antimicrobial potential unloaded (Fr3) and loaded (F9Fr3) into a nanoemulsion (F9) composed of cholesterol as the oil phase (10%), polyoxyethylene 20-cetyl ether and soy phosphatidylcholine (2:1) as surfactant (20%), and a solution of phosphate buffer (pH 7.4) plus chitosan polymer dispersion (0.25%) as the aqueous phase (70%) to use for VVC treatment. Phytochemical procedures showed that Fr3 is rich in luteolin, which is responsible for the antimicrobial activity. F9 development showed satisfactory parameters for use in the vulvovaginal candidiasis (VVC) treatment, as F9 demonstrated pseudoplastic, elastic behavior, and adhesive properties on vaginal mucosa. In addition, we observed improvement in antimicrobial potential of Fr3 on planktonic and biofilms after incorporation in F9. Fr3 and F9Fr3 showed satisfactory parameters related to toxic profiles in cell lines and in a model of acute toxicity by Artemia salina. The in vivo VVC assay showed that F9Fr3 was more active than unloaded Fr3 in VVC treatment. In conclusion, this work showed that use of a fraction rich in luteolin can be a used as an antimicrobial for treatment of vaginal infections and that use of nanostructured lipid systems was an important factor in the biological efficacy of Fr3, especially in treatment of acute VVC.
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Candidiasis Vulvovaginal , Eriocaulaceae , Nanoestructuras , Antiinfecciosos , Femenino , Humanos , Extractos VegetalesRESUMEN
Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-ß and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Malpighiaceae/química , Úlcera Péptica/tratamiento farmacológico , Animales , Antiulcerosos/farmacología , Flavonoides/farmacología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Gastritis/tratamiento farmacológico , Gastritis/metabolismo , Glutatión/metabolismo , Masculino , Medicina Tradicional/métodos , Úlcera Péptica/metabolismo , Fitoquímicos/farmacología , Fitoterapia/métodos , Extractos Vegetales/farmacología , Hojas de la Planta/química , Plantas Medicinales/química , Ratas , Ratas Wistar , Estómago/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The number of bacterial strains that are resistant to multiple conventional antimicrobial agents is increasing. In this context, natural products have been widely used as a strategy to treat diseases caused by bacteria. Infections by Helicobacter pylori have attracted attention because they are directly related to severe gastric medical conditions. Casearia sylvestris Swartz, popularly known as guaçatonga, is largely employed to treat gastric disorders in Brazilian folk medicine. This plant species has aroused much interest mainly because it displays anti-inflammatory activity and can act as an antiulcer agent. AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-H. pylori action of C. sylvestris leaf derivatives incorporated or not in a nanostructured drug delivery system. MATERIALS AND METHODS: The essential oil (obtained by hydrodistillation) and ethanolic extract (obtained by maceration) were obtained from C. sylvestris leaves. The ethanolic extract was submitted to fractionation through solid phase extraction and column chromatography, to yield the ethanolic fractions. Hydrolyzed casearin J was achieved by submitting isolated casearin J to acid hydrolysis. The derivatives were chemically characterized by nuclear magnetic resonance (NMR), gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) analyses. A nanostructured lipid system was used as drug delivery system. To assess the in vitro antibacterial activity of C. sylvestris leaf essential oil, ethanolic extract, and derivatives, microdilution, biofilm, and time-kill assays were performed against H. pylori ATCC 43504. Finally, the in vivo action was investigated by employing male Wistar rats experimentally infected with H. pylori. RESULTS: Many C. sylvestris leaf derivatives presented significant in vitro activity against H. pylori. Among the derivatives, fraction 2 (F2) was the most effective. In vivo tests showed that both the ethanolic extract and F2 decreased the ulcerative lesion size, but only the ethanolic extract eradicated H. pylori from the gastric lesions. Incorporation of plant derivatives in nanostructured lipid system blunted the in vitro action, as demonstrated by the microdilution assay. However, this incorporation improved the ethanolic extract activity against biofilms. CONCLUSION: C. sylvestris leaf derivatives are effective against H. pylori both in vitro and in vivo. According to phytochemical analyses, these derivatives are rich in terpenoids, which could be related to the anti-H. pylori action. Synergism could also underlie C. sylvestris efficacy judging from the fact that the sub-fractions and isolated compounds had lower activity than the extract. Incorporation in a nanostructured lipid system did not improve the activity of the compounds in our in vivo protocol.
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Antibacterianos , Antiulcerosos , Casearia , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Aceites Volátiles , Extractos Vegetales , Úlcera Gástrica/tratamiento farmacológico , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiulcerosos/química , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Brasil , Helicobacter pylori/crecimiento & desarrollo , Masculino , Medicina Tradicional , Aceites Volátiles/química , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas Wistar , Terpenos/análisis , Terpenos/farmacología , Terpenos/uso terapéuticoRESUMEN
Since the dawn of civilization, it has been understood that pathogenic microorganisms cause infectious conditions in humans, which at times, may prove fatal. Among the different virulent properties of microorganisms is their ability to form biofilms, which has been directly related to the development of chronic infections with increased disease severity. A problem in the elimination of such complex structures (biofilms) is resistance to the drugs that are currently used in clinical practice, and therefore, it becomes imperative to search for new compounds that have anti-biofilm activity. In this context, nanotechnology provides secure platforms for targeted delivery of drugs to treat numerous microbial infections that are caused by biofilms. Among the many applications of such nanotechnology-based drug delivery systems is their ability to enhance the bioactive potential of therapeutic agents. The present study reports the use of important nanoparticles, such as liposomes, microemulsions, cyclodextrins, solid lipid nanoparticles, polymeric nanoparticles, and metallic nanoparticles, in controlling microbial biofilms by targeted drug delivery. Such utilization of these nanosystems has led to a better understanding of their applications and their role in combating biofilms.
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Biopelículas/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Humanos , Lípidos/química , Liposomas/administración & dosificación , Liposomas/química , Nanopartículas del Metal/química , Nanopartículas/administración & dosificación , Nanotecnología , Polímeros/químicaRESUMEN
Herbal-loaded drug delivery nanotechnological systems have been extensively studied recently. The antimicrobial activity of medicinal plants has shown better pharmacological action when such plants are loaded into a drug delivery system than when they are not loaded. Syngonanthus nitens Bong. (Rhul.) belongs to the Eriocaulaceae family and presents antiulcerogenic, antioxidant, antibacterial, and antifungal activity. The aim of this study was to evaluate the antifungal activity of Syngonanthus nitens (S. nitens) extract that was not loaded (E) or loaded (SE) into a liquid crystal precursor system (S) for the treatment of vulvovaginal candidiasis (VVC) with Candida albicans. The minimal inhibitory concentration (MIC) was determined by the microdilution technique. Additionally, we performed hyphae inhibition and biofilm tests. Finally, experimental candidiasis was evaluated in in vivo models with Wistar female rats. The results showed effective antifungal activity after incorporation into S for all strains tested, with MICs ranging from 31.2 to 62.5 µg/mL. Microscopic observation of SE revealed an absence of filamentous cells 24 h of exposure to a concentration of 31.2 µg/mL. E demonstrated no effective action against biofilms, though SE showed inhibition against biofilms of all strains. In the in vivo experiment, SE was effective in the treatment of infection after only two days of treatment and was more effective than E and amphotericin B. The S. nitens is active against Candida albicans (C. albicans) and the antifungal potential is being enhanced after incorporation into liquid crystal precursor systems (LCPS). These findings represent a promising application of SE in the treatment of VVC.
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Antifúngicos/uso terapéutico , Candidiasis Vulvovaginal/tratamiento farmacológico , Eriocaulaceae/química , Nanoestructuras/química , Extractos Vegetales/uso terapéutico , Animales , Antifúngicos/química , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Candidiasis Vulvovaginal/microbiología , Sistemas de Liberación de Medicamentos/métodos , Femenino , Extractos Vegetales/química , Ratas , Ratas WistarRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as "cipó-uva" or "cipó-timbó". Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. MATERIAL AND METHODS: We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia-reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE2, vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. RESULTS: The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro. In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro, the extract also displayed evident antimicrobial effects against Helicobacter pylori. However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. CONCLUSIONS: Despite the anti-H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine.
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Antiulcerosos/farmacología , Extractos Vegetales/farmacología , Sapindaceae/química , Úlcera Gástrica/prevención & control , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/toxicidad , Antiulcerosos/aislamiento & purificación , Antiulcerosos/toxicidad , Antidiarreicos/aislamiento & purificación , Antidiarreicos/farmacología , Antidiarreicos/toxicidad , Modelos Animales de Enfermedad , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Masculino , Medicina Tradicional , Ratones , Extractos Vegetales/toxicidad , Hojas de la Planta , Ratas , Ratas Wistar , Factores de Tiempo , Pruebas de Toxicidad AgudaRESUMEN
Vaginal infections caused by Candida krusei are a problem of extreme complexity due to the intrinsic resistance to azole drugs. The species Syngonanthus nitens (Bong.) Ruhland is a plant of the Eriocaulaceae family that has demonstrated promising antifungal activity. In phyto-formulation research, liquid crystal precursor mucoadhesive systems (LCPM) stand out as drug delivery systems for vaginal administration because they increase the activity and overcome the problems associated with plant-based medicines. Therefore, the objective of this study was to evaluate the potential of the methanolic extract of scapes of S. nitens (S. nitens extract [SNE]) and an SNE-loaded LCPM against C. krusei as prophylaxis for vulvovaginal candidiasis. LCPM formulation developed consisted of oleic acid as the oil phase (50% w/w), polyoxypropylene (5) polyoxyethylene (20) cetyl alcohol (40% w/w) as the surfactant and a polymeric dispersion containing 2.5% Carbopol(®) 974P and 2.5% polycarbophil (10% w/w) as the aqueous phase. LCPM formulation developed was characterized using polarized light microscopy, rheological analysis, and in vitro mucoadhesive studies. Different strains of C. krusei, including one standard strain (American Type Culture Collection 6258) and three clinically isolated strains from the vaginal region (CKV1, 2, and 3), were used to determine the minimum inhibitory concentration, inhibition of biofilms, and time kill. The in vivo prophylaxis assay was performed using the standard strain (American Type Culture Collection 6258). The analyses of F by polarized light microscopy and rheology showed isotropy; however, the addition of 100% artificial vaginal mucus (F100) made it more viscous and anisotropic. Moreover, the mucoadhesive strength was modified, which makes F an excellent formulation for vaginal applications. SNE was active against all strains studied, with minimum inhibitory concentration values ranging from 125 to 62.5 µg/mL; after incorporating SNE into F (FE), these values decreased to 62.5 to 31.2 µg/mL, demonstrating that incorporation into the formulation potentiated the action of SNE. Additionally, the time kill assays showed that both forms of SNE were capable of controlling growth, thereby suggesting a possible fungistatic mechanism. Unloaded SNE was not active against C. krusei biofilms, but FE was active against a clinical strain (CKV2). In vivo analysis showed that FE was able to prevent the development of infection following 10 days of administration. We concluded that the formulation developed in this study was an important vehicle for the delivery of SNE based on the improved antifungal activity in all in vitro and in vivo analyses. Furthermore, the extract incorporated into the system may serve as an important prophylactic agent against vaginal infections caused by C. krusei.
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Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Eriocaulaceae/química , Cristales Líquidos , Moco/química , Extractos Vegetales/farmacología , Animales , Profilaxis Antibiótica , Antifúngicos/química , Candidiasis Vulvovaginal/microbiología , Portadores de Fármacos , Femenino , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas WistarRESUMEN
Throughout the genetic and physiological evolution of microorganisms, the microbiological sciences have been expanding the introduction of new therapeutic trials against microbial diseases. Special attention has been paid to the bacterium Helicobacter pylori, which induces gastric infections capable of causing damage, ranging from acute and chronic gastritis to the development of gastric cancer and death. The use of compounds with natural origins has gained popularity in scientific research focused on drug innovation against H. pylori because of their broad flexibility and low toxicity. The aim of this study was to describe the use of natural products against H. pylori in order to clarify important parameters for related fields. The study demonstrated the vast therapeutic possibilities for compounds originating from natural sources and revealed the need for innovations from future investigations to expand the therapeutic arsenal in the fight against H. pylori infection.