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Over recent years, the scientific community has acknowledged the crucial role of certain microbial strains inhabiting the intestinal ecosystem in promoting human health, and participating in various beneficial functions for the host. These microorganisms are now referred to as next-generation probiotics and are currently considered as biotherapeutic products and food or nutraceutical supplements. However, the majority of next-generation probiotic candidates pose nutritional demands and exhibit high sensitivity towards aerobic conditions, leading to numerous technological hurdles in large-scale production. This underscores the need for the development of suitable delivery systems capable of enhancing the viability and functionality of these probiotic strains. Currently, potential candidates for next generation probiotics (NGP) are being sought among gut bacteria linked to health, which include strains from the genera Bacteroids, Faecalibacterium, Akkermansia and Clostridium. In contrast to Lactobacillus spp. and Bifidobacterium spp., NGP, particularly Bacteroids spp. and Clostridium spp., appear to exhibit greater ambiguity regarding their potential to induce infectious diseases. The present review provides a comprehensive overview of NGPs in terms of their health beneficial effects, regulation framework and risk assessment targeting relevant criteria for commercialization in food and pharmaceutical markets.
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Microbes are a worthwhile organism of the earth that could be formulated as consortium which can be utilized as biofertilizers. Consortium-based bioinoculants or biofertilizers are superior to single strain-based inoculants for sustainable agricultural productivity and increased micronutrient content in yield. The aim of present study was to evaluate the effect of different combinations of beneficial bacteria that are more effective than single-based bioinoculants. The current work focuses on the isolation of rhizospheric microorganisms from various cereals and pseudocereal crops and the development of a single inoculum as well as a bacterial consortium which were evaluated on wheat crop. A total 214 rhizospheric bacteria were sorted out and, screened for mineral solubilizing attributes i.e., phosphorus, potassium, zinc and selenium solubilization. Among all the bacterial isolates, four potential strains exhibiting P, K, Zn and Se-solubilizing attributes were identified with the help of 16S rRNA gene sequencing as Rahnella aquatilis EU-A3Rb1, Erwinia aphidicola EU-A2RNL1, Brevibacillus brevis EU-C3SK2, and Bacillus mycoides EU-WRSe4, respectively. The identified strains formulated as a consortium which were found to improve the plant growth and physiological parameters in comparison to single culture inoculants and control. To the best of our knowledge, the present investigation is the first report that has developed the consortium from bacterial strains Rahnella aquatilis EU-A3Rb1, Erwinia aphidicola EU-A2RNL1, Brevibacillus brevis EU-C3SK2, and Bacillus mycoides EU-WRSe4. A combination of bacterial strains could be used as liquid inoculants for cereal crops growing in mountainous regions.
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In the present scenario, growing population demands more food, resulting in the need for sustainable agriculture. Numerous approaches are explored in response to dangers and obstacles to sustainable agriculture. A viable approach is to be exploiting microbial consortium, which generate diverse biostimulants with growth-promoting characteristics for plants. These bioinoculants play an indispensable role in optimizing nutrient uptake efficiency mitigating environmental stress. Plant productivity is mostly determined by the microbial associations that exist at the rhizospheric region of plants. The engineered consortium with multifunctional attributes can be effectively employed to improve crop growth efficacy. A number of approaches have been employed to identify the efficient consortia for plant growth and enhanced crop productivity. Various plant growth-promoting (PGP) microbes with host growth-supporting characteristics were investigated to see if they might work cohesively and provide a cumulative effect for improved growth and crop yield. The effective microbial consortia should be assessed using compatibility tests, pot experimentation techniques, generation time, a novel and quick plant bioassay, and sensitivity to external stimuli (temperature, pH). The mixture of two or more microbial strains found in the root microbiome stimulates plant growth and development. The present review deals with mechanism, formulation, inoculation process, commercialization, and applications of microbial consortia as plant bioinoculants for agricultural sustainability.
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Agricultura , Productos Agrícolas , Consorcios Microbianos , Desarrollo de la Planta , Agricultura/métodos , Productos Agrícolas/microbiología , Microbiología del Suelo , Raíces de Plantas/microbiología , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Rizosfera , Plantas/microbiología , MicrobiotaRESUMEN
Agro-environmental sustainability is based upon the adoption of efficient resources in agro-practices that have a nominal impact on the ecosystem. Insect pests are responsible for causing severe impacts on crop productivity. Wide ranges of agro-chemicals have been employed over the last 50 years to overcome crop yield losses due to insect pests. But better knowledge about the hazards due to chemical pesticides and other pest resistance and resurgence issues necessitates an alternative for pest control. The applications of biological pesticides offer a best alternate that is safe, cost-effective, easy to adoption and successful against various insect pests and pathogens. Like other organisms, insects can get a wide range of diseases from various microbes, such as bacteria, fungi, viruses, protozoa, and nematodes. In order to create agricultural pest management practices that are environmentally beneficial, bacterial entomopathogens are being thoroughly studied. Utilization of bacterial biopesticides has been adopted for the protection of agricultural products. The different types of toxin complexes released by various microorganisms and their mechanisms of action are recapitulated. The present review described the diversity and biocontrol prospective of certain bacteria and summarised the potential of bacterial biopesticides for the management of agricultural pests, insects, and other phytopathogenic microorganisms in agricultural practices.
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Fruit crops are frequently subjected to biotic and abiotic stresses that can significantly reduce the absorption and translocation of essential elements, ultimately leading to a decrease in crop yield. It is imperative to grow fruits and vegetables in areas prone to drought, salinity, and extreme high, and low temperatures to meet the world's minimum nutrient demand. The use of integrated approaches, including supplementation of beneficial elements like silicon (Si), can enhance plant resilience under various stresses. Silicon is the second most abundant element on the earth crust, following oxygen, which plays a significant role in development and promote plant growth. Extensive efforts have been made to explore the advantages of Si supplementation in fruit crops. The application of Si to plants reinforces the cell wall, providing additional support through enhancing a mechanical and biochemical processes, thereby improving the stress tolerance capacity of crops. In this review, the molecular and physiological mechanisms that explain the beneficial effects of Si supplementation in horticultural crop species have been discussed. The review describes the role of Si and its transporters in mitigation of abiotic stress conditions in horticultural plants.
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Productos Agrícolas , Silicio , Estrés Fisiológico , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Frutas/metabolismo , Frutas/crecimiento & desarrolloRESUMEN
In the past few decades, the pressure of higher food production to satisfy the demand of ever rising population has inevitably increased the use synthetic agrochemicals which have deterioration effects. Biostimulants containing beneficial microbes (single inoculants and microbial consortium) were found as an ideal substitute of synthetic chemical fertilizers. In recent years, microbial consortium is known as a better bioinoculant in comparison to single inoculant bioformulation because of multifarious plant growth-promoting advantages. Looking at the advantageous effect of consortium, in present investigation, different bacteria were isolated from rhizospheric soil and plant samples collected from the Himalayan mountains on the green slopes of the Shivaliks, Himachal Pradesh. The isolated bacteria were screened for nitrogen (N) fixation, phosphorus (P) solubilization and potassium (K) solubilization plant growth promoting attributes, and efficient strains were identified through 16S rRNA gene sequencing and BLASTn analysis. The bacteria showing a positive effect in NPK uptake were developed as bacterial consortium for the growth promotion of eggplant crop. A total of 188 rhizospheric and endophytic bacteria were sorted out, among which 13 were exhibiting nitrogenase activity, whereas 43 and 31 were exhibiting P and K solubilization traits, respectively. The selected three efficient and potential bacterial strains were identified using 16S rRNA gene sequencing as Enterobacter ludwigii EU-BEN-22 (N-fixer; 35.68 ± 00.9 nmol C2H4 per mg protein per h), Micrococcus indicus EU-BRP-6 (P-solubilizer; 201 ± 0.004 mg/L), and Pseudomonas gessardii EU-BRK-55 (K-solubilizer; 51.3 ± 1.7 mg/mL), and they were used to develop a bacterial consortium. The bacterial consortium evaluation on eggplant resulted in the improvement of growth (root/shoot length and biomass) and physiological parameters (chlorophyll, carotenoids, total soluble sugar, and phenolic content) of the plants with respect to single culture inoculation, chemical fertilizer, and untreated control. A bacterial consortium having potential to promote plant growth could be used as bioinoculant for horticulture crops growing in hilly regions.
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Oral candidiasis is an infection of the oral cavity commonly caused by Candida albicans. Endodontic treatment failure has also been found to be persistent from C. albicans in the root canal system. Despite the availability of antifungal drugs, the management of Candida oral infection is difficult as it exhibits resistance to a different class of antifungal drugs. Therefore, it is necessary to discover new antifungal compounds to cure fungal infections. This study aimed to examine the antifungal susceptibility of Capsaicin, an active compound of chili pepper. The susceptibility of Capsaicin and Fluconazole was tested against the Candida species by the CLSI (M27-A3) method. The effect of Capsaicin on the fungal cell wall was examined by the ergosterol inhibitory assay and observed by the scanning electron micrograph. The MIC range of Capsaicin against Candida isolates from oral (n = 30), endodontic (n = 8), and ATCC strains (n = 2) was 12.5−50 µg/mL. The MIC range of Fluconazole (128- 4 µg/mL) significantly decreased (2- to 4-fold) after the combination with Capsaicin (MIC/4) (p < 0.05). Capsaicin (at MIC) significantly reduced the mature biofilm of C. albicans by 70 to 89% (p < 0.01). The ergosterol content of the cell wall decreased significantly with the increase in the Capsaicin dose (p < 0.01). Capsaicin showed high sensitivity against the hyphae formation and demonstrated a more than 71% reduction in mature biofilm. A fluorescence microscopy revealed the membrane disruption of Capsaicin-treated C. albicans cells, whereas a micrograph of electron microscopy showed the distorted cells' shape, ruptured cell walls, and shrinkage of cells after the release of intracellular content. The results conclude that Capsaicin had a potential antifungal activity that inhibits the ergosterol biosynthesis in the cell wall, and therefore, the cells' structure and integrity were disrupted. More importantly, Capsaicin synergistically enhanced the Fluconazole antifungal activity, and the synergistic effect might be helpful in the prevention of Fluconazole resistance development and reduced drug-dosing.
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Candida albicans , Candidiasis , Antifúngicos/metabolismo , Fluconazol/metabolismo , Capsaicina/uso terapéutico , Candida , Candidiasis/tratamiento farmacológico , Ergosterol/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
Edible Bird's Nest (EBN) is the most prized health delicacy among the Chinese population in the world. Although some scientific characterization and its bioactivities have been studied and researched, no lights have been shed on its actual composition or mechanism. The aim of this review paper is to address the advances of EBN as a therapeutic animal bioproduct, challenges and future perspectives of research involving EBN. The methodology of this review primarily involved a thorough search from the literature undertaken on Web of Science (WoS) using the keyword "edible bird nest". Other information were obtained from the field/market in Malaysia, one of the largest EBN-producing countries. This article collects and describes the publications related to EBN and its therapeutic with diverse functional values. EBN extracts display anti-aging effects, inhibition of influenza virus infection, alternative traditional medicine in athletes and cancer patients, corneal wound healing effects, stimulation of proliferation of human adipose-derived stem cells, potentiate of mitogenic response, epidermal growth factor-like activities, enhancement of bone strength and dermal thickness, eye care, neuroprotective and antioxidant effects. In-depth literature study based on scientific findings were carried out on EBN and its properties. More importantly, the future direction of EBN in research and development as health-promoting ingredients in food and the potential treatment of certain diseases have been outlined.
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A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF6-), tetrafluoroboron (BF4-) and/or trifluoroacetate (CF3COO-) counter anion, were designed and characterized by IR, NMR and mass spectrometry. The reactions were conducted under both conventional and green ultrasound procedures. The antifungal potential of the synthesized compounds 2-25 was investigated against 40 strains of Candida (four standard and 36 clinical isolates). Minimum inhibitory concentrations (MIC90) of the synthesized compounds were in the range of 62.5-2000 µg/mL for both standard and oral Candida isolates. MIC90 results showed that the synthesized 1-(2-(4-chlorophenyl)-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-pyridin-1-ium hexafluorophosphate (11) was found to be most effective, followed by 4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)-1-(2-(4-nitrophenyl)-2-oxoethyl)-pyridin-1-ium hexafluorophosphate (14) and 1-(2-ethoxy-2-oxoethyl)-4-(2-(4-fluorobenzylidene)hydrazinecarbonyl)pyridin-1-ium hexafluorophosphate (8). All the Candida isolates showed marked sensitivity towards the synthesized compounds. Ergosterol content was drastically reduced by more active synthesized compounds, and agreed well with MIC90 values. Confocal scanning laser microscopy (CLSM) results showed that the red colored fluorescent dye enters the test agent treated cells, which confirms cell wall and cell membrane damage. The microscopy results obtained suggested membrane-located targets for the action of these synthesized compounds. It appears that the test compounds might be interacting with ergosterol in the fungal cell membranes, decreasing the membrane ergosterol content and ultimately leading to membrane disruption as visible in confocal results. The present study indicates that these synthesized compounds show significant antifungal activity against Candida which forms the basis to carry out further in vivo experiments before their clinical use.
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Antifúngicos/síntesis química , Tecnología Química Verde/métodos , Hidrazonas/síntesis química , Compuestos de Piridinio/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Candida/efectos de los fármacos , Hidrazonas/química , Hidrazonas/farmacología , Líquidos Iónicos/síntesis química , Líquidos Iónicos/química , Líquidos Iónicos/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Compuestos de Piridinio/química , Compuestos de Piridinio/farmacologíaRESUMEN
The incidence of oral candidosis has increased in recent years due to the escalation in HIV-infection, cancer treatments, organ transplantation, and diabetes. In addition, corticosteroid use, dentures, and broad-spectrum antibiotic use have also contributed to the problem. Treatment of oral candidosis has continued to be problematic because of the potential toxicity of antifungals in clinical use, and, above all, development of drug resistance among patients. In this study, the antifungal effect of magnolol was investigated against 64 strains of Candida spp. (four standard and 60 oral isolates) through minimum inhibitory concentration (MIC) and growth curve assays. Insight into the mechanisms of the antifungal action has been gained through ultrastructural studies using confocal scanning laser microscopy (CSLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Molecular docking was done for predicting the interactions of magnolol with ergosterol at supramolecular level. The toxicity of magnolol on human erythrocytes was measured by in vitro hemolytic assay. MIC values of magnolol ranged from 16-64 µg/ml, respectively. All tested isolates showed a marked sensitivity towards magnolol in growth curve assays. Biofilm results suggested that magnolol showed strong anti-biofilm activity. The results obtained for four different Candida spp. demonstrated that MBIC values of magnolol showed the average biofilm inhibition by 69.5%, respectively. CLSM experiments showed that cells exposed to magnolol (MIC) exhibited cell membrane disruption. SEM analysis of magnolol treated cells resulted in deformed cells. TEM micrographs showed rupturing of the cell wall and plasma membrane, releasing the intracellular content, and swelling of the cell wall. Hemolytic activity of magnolol is 11.9% at its highest MIC compared to an activity level of 25.4% shown by amphotericin B (Amp B) at 1 µg/ml. Lipinski's parameters calculated for magnolol suggested its good oral bioavailability. Docking studies indicated that magnolol might be interacting with ergosterol in the fungal cell membranes. Together, the present study provides enough evidence for further work on magnolol so that better strategies could be employed to treat oral candidosis.
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Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Candida/efectos de los fármacos , Candidiasis Bucal/tratamiento farmacológico , Lignanos/farmacología , Anfotericina B/farmacología , Biopelículas/crecimiento & desarrollo , Compuestos de Bifenilo/química , Candida/citología , Candida/crecimiento & desarrollo , Candida/aislamiento & purificación , Membrana Celular/efectos de los fármacos , Ergosterol/farmacología , Eritrocitos/efectos de los fármacos , Humanos , Lignanos/química , Pruebas de Sensibilidad Microbiana , Microscopía , Simulación del Acoplamiento MolecularRESUMEN
Edible bird's nest (EBN) is an expensive animal bioproduct due to its reputation as a food and delicacy with diverse medicinal properties. One kilogram of EBN costs ~$6000 in China. EBN and its products are consumed in mostly Asian countries such as China, Hong Kong, Taiwan, Singapore, Malaysia, Indonesia, Vietnam and Thailand, making up almost 1/3 of world population. The rapid growth in EBN consumption has led to a big rise in the trade scale of its global market. Presently, various fake materials such as tremella fungus, pork skin, karaya gum, fish swimming bladder, jelly, agar, monosodium glutamate and egg white are used to adulterate EBNs for earning extra profits. Adulterated or fake EBN may be hazardous to the consumers. Thus, it is necessary to identify of the adulterants. Several sophisticated techniques based on genetics, immunochemistry, spectroscopy, chromatography and gel electrophoresis have been used for the detection of various types of adulterants in EBN. This article describes the recent advances in the authentication methods for EBN. Different genetic, immunochemical, spectroscopic and analytical methods such as genetics (DNA) based techniques, enzyme-linked immunosorbent assays, Fourier transform infrared and Raman spectroscopic techniques, and chromatographic and gel electrophoretic methods have been discussed. Besides, significance of the reported methods that might pertain them to applications in EBN industry has been described. Finally, efforts have been made to discuss the challenges and future perspectives of the authentication methods for EBN.
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Productos Biológicos , Aves , Análisis de los Alimentos/métodos , Alimentos/normas , Animales , Asia Sudoriental , Productos Biológicos/análisis , Productos Biológicos/química , Productos Biológicos/normas , Ensayo de Inmunoadsorción Enzimática , Reacción en Cadena de la Polimerasa , Saliva/química , Análisis EspectralRESUMEN
The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal.
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Acroleína/análogos & derivados , Antifúngicos/farmacología , Acroleína/química , Acroleína/farmacología , Animales , Antifúngicos/química , Sinergismo Farmacológico , Hongos/efectos de los fármacos , Humanos , Estructura Molecular , Levaduras/efectos de los fármacosRESUMEN
In this study, we have used aldehyde function of cinnamaldehyde to synthesize N, N'-Bis (cinnamaldehyde) ethylenediimine [C20H20N2] and Co(II) complex of the type [Co(C40H40N4)Cl2]. The structures of the synthesized compounds were determined on the basis of physiochemical analysis and spectroscopic data ((1)H NMR, FTIR, UV-visible and mass spectra) along with molar conductivity measurements. Anticandidal activity of cinnamaldehyde its ligand [L] and Co(II) complex was investigated by determining MIC80, time-kill kinetics, disc diffusion assay and ergosterol extraction and estimation assay. Ligand [L] and Co(II) complex are found to be 4.55 and 21.0 folds more efficient than cinnamaldehyde in a liquid medium. MIC80 of Co(II) complex correlated well with ergosterol inhibition suggesting ergosterol biosynthesis to be the primary site of action. In comparison to fluconazole, the test compounds showed limited toxicity against H9c2 rat cardiac myoblasts. In confocal microscopy propidium iodide (PI) penetrates the yeast cells when treated with MIC of metal complex, indicating a disruption of cell membrane that results in imbibition of dye. TEM analysis of metal complex treated cells exhibited notable alterations or damage to the cell membrane and the cell wall. The structural disorganization within the cell cytoplasm was noted. It was concluded that fungicidal activity of Co(II) complex originated from loss of membrane integrity and a decrease in ergosterol content is only one consequence of this.
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Acroleína/análogos & derivados , Cobalto/farmacología , Ergosterol/biosíntesis , Fungicidas Industriales/farmacología , Acroleína/farmacología , Animales , Línea Celular , Cobalto/química , Ligandos , Microscopía Electrónica de Transmisión , Espectroscopía de Protones por Resonancia Magnética , Ratas , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría InfrarrojaRESUMEN
The antifungal effects of cinnamaldehyde, 4-hydroxy-3-methoxycinnamaldehyde (coniferyl aldehyde) and 3,5-dimethoxy-4-hydroxycinnamaldehyde (sinapaldehyde) were investigated against 65 strains of Candida (six standard, 39 fluconazole-sensitive and 20 fluconazole-resistant). MICs of cinnamaldehyde, coniferyl aldehyde and sinapaldehyde ranged from 100 to 500 µg ml(-1), 100 to 300 µg ml(-1) and 100 to 200 µg ml(-1), respectively. All tested isolates showed a marked sensitivity towards these aldehydes in spot and time-kill assays. Sinapaldehyde was found to be the most effective, followed by coniferyl aldehyde and cinnamaldehyde. At their respective MIC(90) values, the three compounds caused mean inhibition levels of glucose-stimulated H(+)-efflux of 36, 34 and 41â% (cinnamaldehyde), 41, 42 and 47â% (coniferyl aldehyde) and 43, 45 and 51â% (sinapaldehyde) for standard-sensitive, clinical-sensitive and clinical-resistant isolates, respectively. Inhibition levels of H(+)-efflux caused by plasma membrane ATPase inhibitors N,N'-dicyclohexylcarbodiimide (100 µM) and diethylstilbestrol (10 µM) were 34, 45 and 44â%, and 57, 39 and 35â%, for standard-sensitive, clinical-sensitive and clinical-resistant isolates, respectively. Intracellular pH (pHi) was found to decrease by 0.34, 0.42 and 0.50 units following incubation with three tested aldehydes from the control pHi of 6.70. Scanning electron microscopy and transmission electron microscopy analysis was performed on a representative strain, C. albicans 10261, showing alterations in morphology, cell wall, plasma membrane damage and lysis. Haemolytic activity of the three compounds varied from 10 to 15â% at their highest MIC compared to an activity level of 20â% shown by fluconazole at 30 µg ml(-1). In conclusion, this study shows significant activity of cinnamic aldehydes against Candida, including azole-resistant strains, suggesting that these molecules can be developed as antifungals.
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Acroleína/análogos & derivados , Candida/efectos de los fármacos , Transporte Iónico/efectos de los fármacos , Protones , Acroleína/farmacología , Antifúngicos/farmacología , Candida/metabolismo , Candida/ultraestructura , Membrana Celular/efectos de los fármacos , Pared Celular/efectos de los fármacos , Diciclohexilcarbodiimida/farmacología , Dietilestilbestrol/farmacología , Eritrocitos/efectos de los fármacos , Fluconazol/farmacología , Glucosa/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
Azoles are generally fungistatic, and resistance to fluconazole is emerging in several fungal pathogens. We designed a series of cinnamaldehyde based sulfonyl tetrazole derivatives. To further explore the antifungal activity, in vitro studies were conducted against 60 clinical isolates and 6 standard laboratory strains of Candida. The rapid irreversible action of these compounds on fungal cells suggested a membrane-located target for their action. Results obtained indicate plasma membrane H(+)-ATPase as site of action of the synthesized compounds. Inhibition of H(+)-ATPase leads to intracellular acidification and cell death. Presence of chloro and nitro groups on the sulfonyl pendant has been demonstrated to be a key structural element of antifungal potency. SEM micrographs of treated Candida cells showed severe cell breakage and alterations in morphology.
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Acroleína/análogos & derivados , Antifúngicos/farmacología , ATPasas de Translocación de Protón/antagonistas & inhibidores , Tetrazoles/farmacología , Acroleína/química , Acroleína/farmacología , Antifúngicos/química , Tetrazoles/químicaRESUMEN
Effect of cinnamaldehyde (CD), 4-hydroxy-3-methoxy cinnamaldehyde (HMCD) and 3,5-dimethoxy-4-hydroxy cinnamaldehyde (HDMCD) on growth and virulence factors of standard (Candida albicans 90028) and 26 oral isolates of C. albicans has been investigated. Growth was significantly inhibited by all three compounds in both solid and liquid medium, no systematic difference was observed between various isolates. MIC90 ranged from 125 to 450 µg/ml for CD, 100-250 µg/ml for HMCD and 62.5-125 µg/ml for HDMCD. All oral isolates were found to be proteinase and phospholipase secretors, both proteinase and phospholipase secretion was significantly inhibited by all the three tested molecules. No systematic difference in secretion or its inhibition was observed between standard and oral isolates as also between various isolates. Average drop in proteinase and phospholipase secretion caused by ½ MIC of CD was 33% and 28%, HMCD; 46% and 44%, HDMCD; 59% and 54%. The standard strain and all the 26 oral isolates displayed morphogenesis under triggering experimental conditions; no difference was seen between standard and various isolates. In the absence of test compounds hyphae development at 300 min was 83% for standard strain whereas average hyphae development for oral isolates was 85%. Average hyphal transition was suppressed by all tested compounds. At ½ MIC concentration at 300 min average hyphal transition of standard and oral isolates was CD; 49% and 57%, HMCD; 45% and 38%, HDMCD; 5% and 5%. Average haemolytic activity of the three tested compounds varied from 10 to 15% at their highest MIC compared to 20% shown by fluconazole at typical MIC of 30 µg/ml.
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Acroleína/análogos & derivados , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Candidiasis Bucal/microbiología , Proteínas Fúngicas/metabolismo , Acroleína/farmacología , Candida albicans/enzimología , Candida albicans/aislamiento & purificación , Humanos , Hifa/efectos de los fármacos , Hifa/enzimología , Hifa/genética , Hifa/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Péptido Hidrolasas/metabolismo , Fosfolipasas/metabolismo , Transporte de ProteínasRESUMEN
Cinnamaldehyde, its derivatives and curcumin are reported to have strong antifungal activity. In this work we report and compare anticandidal activity of curcumin (CUR) and α-methyl cinnamaldehyde (MCD) against 38 strains of Candida (3; standard, fluconazole sensitive, 24; clinical, fluconazole sensitive, 11; clinical, fluconazole resistant). The minimum inhibitory concentrations (MIC90) of CUR ranged from 250 to 650 µg/ml for sensitive strains and from 250 to 500 µg/ml for resistant strains. MIC90 of MCD varied between 100 and 250 µg/ml and 100-200 µg/ml for sensitive and resistant strains, respectively. Higher activity of MCD as compared to CUR was further reinforced by spot assays and growth curve studies. At their respective MIC90 values, in the presence of glucose, average inhibition of H+-efflux caused by CUR and MCD against standard, clinical and resistant isolates was 24%, 31%, 32% and 54%, 52%, 54%, respectively. Inhibition of H+-extrusion leads to intracellular acidification and cell death, average pHi for control, CUR and MCD exposed cells was 6.68, 6.39 and 6.20, respectively. Scanning electron micrographs of treated cells show more extensive damage in case of MCD. Haemolytic activity of CUR and MCD at their highest MIC was 11.45% and 13.00%, respectively as against 20% shown by fluconazole at typical MIC of 30 µg/ml. In conclusion, this study shows significant anticandidal activity of CUR and MCD against both azole-resistant and sensitive clinical isolates, MCD is found to be more effective.
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Acroleína/análogos & derivados , Antifúngicos/farmacología , Candida/efectos de los fármacos , Curcumina/farmacología , Resistencia a Medicamentos/efectos de los fármacos , Extractos Vegetales/farmacología , Acroleína/farmacología , Candida/patogenicidad , Eritrocitos/efectos de los fármacos , Fluconazol/farmacología , Hemólisis/efectos de los fármacos , HumanosRESUMEN
This work evaluates the antifungal activity of two essential oil components against 28 clinical isolates (17 sensitive, 11 resistant) and 3 standard laboratory strains of Candida. Growth of the organisms was significantly effected in both solid and liquid media at different test compound concentrations. The minimum inhibitory concentrations (MICs) of Isoeugenol (compound 1) against 31 strains of Candida ranged 100-250 µg/ml and those of o -methoxy cinnamaldehyde (compound 2) ranged 200-500 µg/ml, respectively. Insight studies to mechanism suggested that these compounds exert antifungal activity by targeting H(+)-ATPase located in the membranes of pathogenic Candida species. At their respective MIC(90) average inhibition of H(+)-efflux for standard, clinical and resistant isolates caused by compound 1 and compound 2 was 70%, 74%, 82% and 42%, 42% and 43%. Respective inhibition of H(+)-efflux by fluconazole (5 µg/ml) was 94%, 92% and 10%. Inhibition of H(+)-ATPase leads to intracellular acidification and cell death. SEM analysis of Candida cells showed cell membrane breakage and alterations in morphology. Haemolytic activity on human erythrocytes was studied to exclude the possibility of further associated cytotoxicity.
Asunto(s)
Antifúngicos/metabolismo , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/enzimología , Aceites Volátiles/metabolismo , Aceites Volátiles/farmacología , ATPasas de Translocación de Protón/metabolismo , Acroleína/análogos & derivados , Acroleína/metabolismo , Acroleína/farmacología , Candida/crecimiento & desarrollo , Candida/aislamiento & purificación , Candidiasis/microbiología , Eritrocitos/efectos de los fármacos , Eugenol/análogos & derivados , Eugenol/metabolismo , Eugenol/farmacología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
p-Anisaldehyde (4-methoxybenzaldehyde), an extract from Pimpinella anisum seeds, is a very common digestive herb of north India. Antifungal activity of p-anisaldehyde was investigated on 10 fluconazole-resistant and 5 fluconazole-sensitive Candida strains. Minimum inhibitory concentrations (MIC(90)) ranged from 250 µg/ml to 600 µg/ml for both sensitive and resistant strains. Ergosterol content was drastically reduced by p-anisaldehyde-62% in sensitive and 66% in resistant strains-but did not corelate well with MIC(90) values. It appears that p-anisaldehyde exerts its antifungal effect by decreasing NADPH routed through up-regulation of putative aryl-alcohol dehydrogenases. Cellular toxicity of p-anisaldehyde against H9c2 rat cardiac myoblasts was less than 20% at the highest MIC value. These findings encourage further development of p-anisaldehyde.
Asunto(s)
Antifúngicos/farmacología , Benzaldehídos/farmacología , Candida/crecimiento & desarrollo , Candida/metabolismo , Ergosterol/biosíntesis , Extractos Vegetales/farmacología , Animales , Antifúngicos/aislamiento & purificación , Benzaldehídos/aislamiento & purificación , Benzaldehídos/toxicidad , Candida/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ergosterol/antagonistas & inhibidores , India , Pruebas de Sensibilidad Microbiana , Mioblastos/efectos de los fármacos , NADP/antagonistas & inhibidores , Pimpinella/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , RatasRESUMEN
Attention has been drawn to evaluate the antifungal activity of p-anisaldehyde (1), o-anisaldehyde (2) and m-anisaldehyde (3). To put forward this approach, antifungal activity has been assessed in thirty six fluconazole-sensitive and eleven fluconazole-resistant Candida isolates. Growth and sensitivity of the organisms were significantly effected by test compounds at different concentrations. The rapid irreversible action of compound-1, compound-2 and compound-3 on fungal cells suggested a membrane-located target for their action. We investigated their effect on H(+) ATPase mediated H(+)-pumping by various Candida species. All the compounds inhibit H(+)- ATPase activity at their respective MIC(90) values. Inhibition of H(+) ATPase leads to intracellular acidification and cell death. Scanning electron microscopy analysis revealed deep wrinkles, deformity and flowed content. Furthermore, it was also observed that position of methoxy group attached to the benzene ring decides antifungal activity of the compound. The present study indicates that compound-1, compound-2 and compound-3 have significant antifungal activity against Candida, including azole-resistant strains, advocating further investigation for clinical applications in the treatment of fungal infections.