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The phenolic composition of virgin olive oil (VOO) primarily depends on the phenolic content of the olive fruit. The purpose of this work was to characterize the first metabolic step in the synthesis of tyrosol (Ty) and hydroxytyrosol (HTy), whose derivatives are by far the predominant phenolics in both olive fruit and VOO. To this end, two genes encoding tyrosine/DOPA decarboxylase enzymes, OeTDC1 and OeTDC2, have been identified and functionally and physiologically characterized. Both olive TDC proteins exclusively accept aromatic amino acids with phenolic side chains, such as tyrosine and 3,4-dihydroxyphenylalanine (DOPA), as substrates to produce tyramine and dopamine, respectively. These proteins exhibited a higher affinity for DOPA than for tyrosine, and the catalytic efficiency of both proteins was greater when DOPA was used as a substrate. Both olive TDC genes showed a fairly similar expression profile during olive fruit ontogeny, with OeTDC1 consistently expressed at higher levels than OeTDC2. Expression was particularly intense during the first few weeks after fruit set, coinciding with the active accumulation of Ty and HTy derivatives. The data suggest that both olive TDCs are responsible for the initial step in the synthesis of the most important phenolics, both quantitatively and functionally, in VOO.
Assuntos
Frutas , Olea , Azeite de Oliva , Fenóis , Tirosina Descarboxilase , Olea/genética , Olea/enzimologia , Olea/metabolismo , Azeite de Oliva/metabolismo , Azeite de Oliva/química , Frutas/metabolismo , Frutas/genética , Fenóis/metabolismo , Tirosina Descarboxilase/metabolismo , Tirosina Descarboxilase/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Álcool Feniletílico/metabolismo , Álcool Feniletílico/análogos & derivadosRESUMO
The Mediterranean diet and consumption of EVOO are associated with multiple beneficial effects for human health, e.g. reduction in cardiovascular risk and mortality, improvement in the lipid profile, and the prevention of chronic diseases, such as cancers and neurodegenerative diseases. In EVOO, more than 30 different phenolic-derived compounds have been identified, representing one of the most promising bioactive classes in olive oil. This review explores the hepatoprotective properties of two of these compounds, tyrosol and oleocanthal, focusing on their mechanisms of action. Recent studies have shown that these compounds, which share a similar chemical structure with a hydroxyl group attached to an aromatic hydrocarbon ring, can potentially mitigate chronic liver diseases, such as MASLD and liver fibrosis, as well as their progression to liver cancer. Consequently, they deserve attention for future pharmacological drug development. In vitro and in vivo studies have suggested that these compounds exert these effects through the regulation of cellular pathways involved in antioxidant response, lipid metabolism, transcription factor activity, and NF-κB signaling. Understanding the mechanisms underlying the hepatoprotective properties of tyrosol and oleocanthal may provide valuable information for the development of therapeutic agents based on their chemical structures capable of targeting chronic liver diseases.
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Tyrosol and hydroxytyrosol are powerful phenolic antioxidants occurring in olive oil and in by-products from olive processing. Due to their high polarity, esterification or other lipophilization is necessary to make them compatible with lipid matrices. Hydroxytyrosol methyl carbonate is a more effective antioxidant than dibutylhydroxytoluene or α-tocopherol and together with tyrosol methyl carbonate exerts interesting pharmacological properties. The purpose of this work was the enzymatic preparation of alkyl carbonates of tyrosol and hydroxytyrosol. A set of 17 hydrolases was tested in the catalysis of tyrosol methoxycarbonylation in neat dimethyl carbonate to find an economically feasible alternative to the recently reported synthesis of methyl carbonates catalyzed by Novozym 435. Novozym 435 was, however, found to be the best performing catalyst, while Novozym 735, pig pancreatic lipase, lipase F-AK and Lipex 100T exhibited limited reactivity. No enzyme accepted 1,2-propylene carbonate as the acylation donor. Under optimized reaction conditions, Novozym 435 was used in the batch preparation of tyrosol methyl carbonate and hydroxytyrosol methyl carbonate in quantitative yields. The enzymatic methoxycarbonylation of tyrosol and hydroxytyrosol can also be used as a method for their selective protection in enzymatic syntheses of phenylethanoid glycosides catalyzed with enzymes comprising high levels of acetyl esterase side activity.
Assuntos
Enzimas Imobilizadas , Proteínas Fúngicas , Lipase , Álcool Feniletílico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/metabolismo , Álcool Feniletílico/química , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Lipase/química , Animais , Antioxidantes/química , Suínos , Carbonatos/química , Hidrolases/metabolismoRESUMO
Tyrosol (Ty) and its derivatives have gathered considerable attention in recent years due to their diverse pharmacological properties and potential therapeutic applications. This comprehensive review aims to summarize the current understanding of the therapeutic potential of Ty and its derivatives in combating various diseases, including cancer, cardiovascular disease (CVD), neurodegenerative diseases, diabetes, and obesity. This review highlights the multifaceted properties of Ty, including its pharmacokinetic profile and pharmacological actions, which contribute to its efficacy against these prevalent health conditions. Moreover, the antimicrobial and wound-healing effects of Ty are explored, elucidating its potential for broader therapeutic utilization. While existing studies provide evidence supporting the beneficial effects of Ty, gaps remain in our understanding of its molecular mechanisms of action and the exploration of novel derivatives. Future research efforts are thus critical for unraveling the full therapeutic potential of Ty and its derivatives. Moreover, the synthesis of novel derivatives with enhanced efficacy and improved bioavailability shows potential for addressing unmet medical needs. This review emphasizes the necessity for ongoing research into Ty and its derivatives, providing valuable insights into their potential as essential therapeutic agents for addressing diverse health conditions.
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Mediterranean diet is frequently associated with longevity and a lower incidence of adverse cardiovascular events because of the biological activities and health effects of olives - its key component. Olive oil, olive leaf extract, fruits and different by-products contain many bioactive components that exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. In this review, we focus on the recent studies exploring molecular mechanisms underlying the cardioprotective properties of different olive oils, olive leave extracts, and specific micro-constituents (such as oleuropein, tyrosol, hydroxytyrosol and others) in vitro on rodent models and in clinical trials on human subjects. Particularly, hydroxytyrosol and oleuropein were identified as the major bioactive compounds responsible for the antioxidant, anti-inflammatory, anti-platelet aggregation and anti-atherogenic activities of olive oil. In total, the discussed results demonstrated a positive association between the consumption of olive oil and improvement in outcomes in atherosclerosis, diabetes, myocardial infarction, heart failure, hypertension and obesity.
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Aterosclerose , Olea , Compostos Fitoquímicos , Humanos , Olea/química , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Azeite de Oliva/química , Azeite de Oliva/farmacologiaRESUMO
Tyrosol is a natural phenolic compound with antioxidant, anti-inflammatory and other biological activities, serving as an important precursor of high-value products such as hydroxytyrosol and salidroside. Therefore, the green and efficient biosynthesis of tyrosol and its derivatives has become a research hotspot in recent years. Building cell factories by metabolic engineering of microorganisms is a potential industrial production way, which has low costs and environmental friendliness. This paper introduces the biosynthesis pathway of tyrosol and presents the key regulated nodes in the de novo synthesis of tyrosol in Escherichia coli and Saccharomyces cerevisiae. In addition, this paper reviews the recent advances in metabolic engineering for the production of hydroxytyrosol and salidroside. This review can provide a reference for engineering the strains for the high-yield production of tyrosol and its derivatives.
Assuntos
Escherichia coli , Engenharia Metabólica , Álcool Feniletílico , Saccharomyces cerevisiae , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/metabolismo , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Fenóis/metabolismo , Glucosídeos/biossíntese , Glucosídeos/metabolismo , Microbiologia IndustrialRESUMO
Utilizing Density Functional Theory (DFT) calculations at the B3LYP/QZVP level and incorporating the Conductor-like Polarizable Continuum Model (C-PCM) for solvation, the thermodynamic and chemical activity properties of 21-(hydroxymethoxy)henicosadecaenal, identified in cultured freshwater pearls from the mollusk Hyriopsis cumingii, have been elucidated. The study demonstrates that this compound releases formaldehyde, a potent antimicrobial agent, through dehydrogenation and deprotonation processes in both hydrophilic and lipophilic environments. Moreover, this polyenal exhibits strong anti-reductant properties, effectively scavenging free radicals. These critical properties classify the pearl-derived ingredient as a natural multi-functional compound, serving as a coloring, antiradical, and antimicrobial agent. The 2-(hydroxymethoxy)vinyl (HMV) moiety responsible for the formaldehyde release can be transferred to other compounds, thereby enhancing their biological activity. For instance, tyrosol (4-(2-hydroxyethyl)phenol) can be modified by substituting the less active 2-hydroxyethyl group with the active HMV one, and hinokitiol (4-isopropylotropolone) can be functionalized by attaching this moiety to the tropolone ring. A new type of meso-carrier, structurally modeled on pearls, with active substances loaded both in the layers and the mineral part, has been proposed.
Assuntos
Álcool Feniletílico , Tropolona , Tropolona/análogos & derivados , Tropolona/química , Tropolona/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Monoterpenos/química , Monoterpenos/farmacologia , Formaldeído/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Estrutura Molecular , TermodinâmicaRESUMO
BACKGROUND: Hydroxytyrosol (HT) is a bioactive compound present in a limited number of foods such as wines, olives, and olive oils. During alcoholic fermentation, yeast converts aromatic amino acids into higher alcohols such as tyrosol, which can undergo hydroxylation into HT. The aim of this study was to validate an analytical method using ultra performance liquid chromatography coupled with mass spectrometry (UPLC/MS-MS) to quantify HT and its precursors (tyrosine, hydroxyphenylpyruvic acid, hydroxyphenylacetaldehyde, 4-hydroxyphenylacetic acid, and tyrosol) in wines. Their occurrence was evaluated in a total of 108 commercial Spanish wine samples. RESULTS: The validated method simultaneously determined both HT and its precursors, with adequate limits of detection between 0.065 and 21.86 ng mL-1 and quantification limits between 0.199 and 66.27 ng mL-1 in a 5 min run. The concentration of HT in red wines was significantly higher (0.12-2.24 mg L-1) than in white wines (0.01-1.27 mg L-1). The higher the alcoholic degree, the higher was the content of HT. The bioactive 4-hydroxyphenylacetic acid was identified in Spanish wines for the first time at 3.90-127.47 mg L-1, being present in all the samples. CONCLUSION: The highest HT concentrations were found in red wines and in wines with higher ethanol content. These data are useful for a further estimation of the intake of these bioactive compounds and to enlarge knowledge on chemical composition of wines. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
RESUMO
Peripheral nerve injuries, predominantly affecting individuals aged 20-40, pose significant healthcare challenges, with current surgical methods often failing to achieve complete functional recovery. This study focuses on the development of 3D printed hydrogel nerve conduits using modified hyaluronic acid (HA) for potentially enhancing peripheral nerve regeneration. Hyaluronic acid was chemically altered with cysteamine HCl and methacrylic anhydride to create thiolated HA (HA-SH) and methacrylated HA (HA-MA), achieving a modification degree of approximately 20 %. This modification was crucial to maintain the receptor interaction of HA. The modified HA was rigorously tested to ensure cytocompatibility in neuronal and glial cell lines. Subsequently, various 3D printed HA formulations were evaluated, focusing on improving HA's inherent mechanical weaknesses. These formulations were assessed for cytotoxicity through direct contact and elution extract testing, confirming their safety over a 24-h period. Among the neurotrophic compounds tested, Tyrosol emerged as the most effective in promoting Schwann cell proliferation in vitro. The 3D printed HA system demonstrated proficiency in loading and releasing Tyrosol at physiological pH. The findings from this research highlight the promising role of 3D printed HA and Tyrosol in the field of nerve tissue engineering, offering a novel approach to peripheral nerve regeneration.
Assuntos
Proliferação de Células , Ácido Hialurônico , Regeneração Nervosa , Impressão Tridimensional , Células de Schwann , Células de Schwann/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Animais , Linhagem Celular , Hidrogéis/química , Hidrogéis/administração & dosagem , Humanos , Ratos , Engenharia Tecidual/métodos , Traumatismos dos Nervos Periféricos/tratamento farmacológicoRESUMO
Olive anthracnose, caused by Colletotrichum fungi, and the olive fruit fly Bactrocera olea are, respectively, the most important fungal disease and pest affecting olive fruits worldwide, leading to detrimental effects on the yield and quality of fruits and olive oil. This study focuses on the content of hydroxytyrosol (HYT) and its derivatives (the "olive oil polyphenols" health claim) in olive oils extracted from fruits of 'Galega Vulgar' and 'Cobrançosa' cultivars, naturally affected by olive anthracnose and olive fly. The olives, with different damage levels, were harvested from organic rainfed orchards, located in the center of Portugal, at four harvest times over three years. Galega oils extracted from olives with a higher anthracnose and olive fly incidence showed no conformity for the extra virgin olive oil (EVOO) and virgin olive oil (VOO) categories, presenting high acidity and negative sensory notes accompanied by the disappearance of oleacein. Conversely, no sensory defects were observed in Cobrançosa oils, regardless of disease and pest incidence levels, and quality criteria were still in accordance with the EVOO category. The total HYT and tyrosol (TYR) content (>5 mg/20 g) allows for the use of the "olive oil polyphenols" health claim on the label of all the analyzed Cobrançosa olive oils.
RESUMO
An eco-friendly approach towards the recovery of value-added extracts from olive tree leaves with the aid of supercritical CO2 at 30 MPa was carried out. The impact of extraction temperature (35-90 °C) and presence of co-solvents (ethanol, water, and aqueous ethanol) on the total phenolic, flavonoid, and pigment content, as well as oleuropein, hydroxytyrosol, tyrosol, and α-tocopherol content was determined. In addition, the antioxidant activity of extracts from tree leaves using DPPH, ABTS, and CUPRAC assays was investigated. The results of the study showed that the most effective supercritical CO2 extraction was at 90 °C with an addition of ethanol, which enabled the separation of extract with the highest content of tested compounds. Some of the highest recorded values were for oleuropein 1.9 mg/g, for carotenoids 5.3 mg/g, and for α-tocopherol 2.0 mg/g. Our results are expected to contribute to the efforts towards the valorization of olive leaves as a sustainable source of valuable compounds, and boost local economies as well as the interest of pharmaceutical, food, and cosmetic industries for novel food by-product applications.
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Bioactive compounds that can be recovered by the solid wastes of the olive oil sector, such as polyphenols, are known for their significant antioxidant and antimicrobial activities with potential application in nutraceutical, cosmetic, and food industries. Given that industrial demands are growing, and the polyphenol market value is ever increasing, a systematic study on the recovery of natural antioxidant compounds from olive pomace using ultrasound-assisted extraction (UAE) was conducted. Single-factor parameters, i.e., the extraction solvent, time, and solid-to-liquid ratio, were investigated evaluating the total phenolic content (TPC) recovery and the antioxidant activity of the final extract. The acetone-water system (50% v/v, 20 min, 1:20 g mL-1) exhibited the highest total phenolic content recovery (168.8 ± 5.5 mg GAE per g of dry extract). The olive pomace extract (OPE) was further assessed for its antioxidant and antibacterial activities. In DPPH, ABTS, and CUPRAC, OPE exhibited an antioxidant capacity of 413.6 ± 1.9, 162.72 ± 3.36 and 384.9 ± 7.86 mg TE per g of dry extract, respectively. The antibacterial study showed that OPE attained a minimum inhibitory activity (MIC) of 2.5 mg mL-1 against E. coli and 10 mg mL-1 against B. subtilis. Hydroxytyrosol and tyrosol were identified as the major phenolic compounds of OPE. Furthermore, active chitosan-polyvinyl alcohol (CHT/PVA) films were prepared using different OPE loadings (0.01-0.1%, w/v). OPE-enriched films showed a dose-dependent antiradical scavenging activity reaching 85.7 ± 4.6% (ABTS) and inhibition growth up to 81% against B. subtilis compared to the control film. Increased UV light barrier ability was also observed for the films containing OPE. These results indicate that OPE is a valuable source of phenolic compounds with promising biological activities that can be exploited for developing multifunctional food packaging materials.
Assuntos
Antibacterianos , Antioxidantes , Olea , Fenóis , Extratos Vegetais , Olea/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fenóis/análise , Embalagem de Alimentos , Polifenóis/química , Polifenóis/farmacologia , Polifenóis/isolamento & purificação , Ondas Ultrassônicas , Testes de Sensibilidade MicrobianaRESUMO
Monovarietal olive oils, known for their distinct aromatic profiles, face challenges in preserving their initial quality due to variations in stability and susceptibility to oxidative deterioration. This study focused on the storage stability of two Italian cultivars, 'Biancolilla' and 'Cerasuola', from Sicily, chosen for their aromatic complexity and divergent storage stability. Oils, whether filtered or unfiltered, underwent storage at two thermal regimes (18 °C and - 20 °C) over a year. The combination of filtration and low-temperature storage was employed to mitigate oxidative deterioration and hydrolytic processes, as filtration removes suspended particles and emulsified water, while low temperatures slow down enzymatic activities and oxidative reactions, thereby enhancing the overall stability and shelf life of the olive oils. Unfiltered samples at room temperature showed a significant increase in secoiridoid aglycone derivatives (Hydroxytyrosol and Tyrosol) due to hydrolytic processes, along with a decrease in secoiridoid aglycone. Filtration delayed these processes, with a more pronounced effect observed when combined with -20 °C storage. Sensory analysis identified the emergence of the "fusty" defect in the less resilient 'Biancolilla' cultivar after six months, a phenomenon mitigated by filtration and freezing. Consumer tests validated these findings. In summary, the synergistic approach of combining filtration with low-temperature storage emerges as a promising strategy for maintaining high-quality standards, especially for less stable monovarietal extra virgin olive oils. This strategy ensures compliance with EU regulations beyond the conventional 12-month shelf life, offering a practical solution for preserving the nutritional and sensory quality of olive oil.
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We aimed to study the potential of epigallocatechin-3-gallate/tyrosol-loaded chitosan/lecithin nanoparticles (EGCG/tyrosol-loaded C/L NPs) in streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The EGCG/tyrosol-loaded C/L NPs were created using the self-assembly method. Dynamic light scattering, Field Emission Scanning Electron Microscopy, and Fourier transform infrared spectroscopy were utilized to characterize the nanoparticle. Furthermore, in streptozotocin-induced T2DM mice, treatment with EGCG/tyrosol-loaded C/L NPs on fasting blood sugar levels, the expression of PCK1 and G6Pase, and IL-1ß in the liver, liver glutathione content, nanoparticle toxicity on liver cells, and liver reactive oxygen species were measured. Our findings showed that EGCG/tyrosol-loaded C/L NPs had a uniform size distribution, and encapsulation efficiencies of 84 % and 89.1 % for tyrosol and EGCG, respectively. The nanoparticles inhibited PANC-1 cells without affecting normal HFF cells. Furthermore, EGCG/tyrosol-loaded C/L NP treatment reduced fasting blood sugar levels, elevated hepatic glutathione levels, enhanced liver cell viability, and decreased reactive oxygen species levels in diabetic mice. The expression of gluconeogenesis-related genes (PCK1 and G6 Pase) and the inflammatory gene IL-1ß was downregulated by EGCG/tyrosol-loaded C/L NPs. In conclusion, the EGCG/tyrosol-loaded C/L NPs reduced hyperglycemia, oxidative stress, and inflammation in diabetic mice. These findings suggest that EGCG/tyrosol-loaded C/L NPs could be a promising therapeutic option for type 2 diabetes management.
Assuntos
Catequina , Quitosana , Diabetes Mellitus Experimental , Hiperglicemia , Fígado , Nanopartículas , Animais , Quitosana/química , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hiperglicemia/tratamento farmacológico , Masculino , Glicemia , Estreptozocina , Espécies Reativas de Oxigênio/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Glutationa/metabolismoRESUMO
Green pesticides, derived from natural sources, have gained wider attention as an alternative to synthetic pesticides for managing polyphagous pests, such as Spodoptera litura. In this study, the methanolic flower extract of Nyctanthes arbor-tristis (Mx-Na-t) was subjected to chemical screening, and 3-hydroxy-1,2-dimethyl-4(1H)-pyridone (3H-dp) and tyrosol (Ty-ol) were identified as the major derivatives. The toxic effects of Mx-Na-t (500 ppm) were highest in third-instar S. litura larvae (96.4%), while those of 3H-dp and Ty-ol (5 ppm) were highest in second-instar larvae (76.5% and 81.4%, respectively). The growth and development of S. litura larvae and pupae were significantly reduced by all three treatments. Fecundity rates were also reduced by all treatments [from 1020 eggs (control) to 540 eggs by Mx-Na-t treatment, 741 eggs by 3H-dp treatment, and 721 eggs by Ty-ol treatment]. The extract and its active constituents decreased adult emergence and slowed total larval development in a dose-dependent manner. A decrease was noted in the major gut enzymes of young S. litura larvae exposed to Mx-Na-t, 3H-dp, and Ty-ol. Moreover, midgut tissues of fourth-instar larvae were severely damaged by Mx-Na-t (250 ppm), 3H-dp (2.5 ppm), and Ty-ol (2.5 ppm); the treatments induced structural damage to the epithelial cells and gut lumen. The earthworm Eisenia fetida was used to assess nontarget toxicity. Compared with cypermethrin, the phytochemicals exhibited minimal effects on the earthworm's detoxifying enzymes superoxide dismutase and catalase after 14 days of treatment. Moreover, in silico predictions using BeeTox and ProTox-II indicated little or no toxicity of 3H-dp and Ty-ol toward honey bees and other nontarget species.
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Flores , Larva , Oligoquetos , Extratos Vegetais , Spodoptera , Animais , Spodoptera/efeitos dos fármacos , Oligoquetos/efeitos dos fármacos , Extratos Vegetais/toxicidade , Larva/efeitos dos fármacos , Flores/química , Inibidores Enzimáticos/toxicidadeRESUMO
Although tyrosol is a quorum-sensing molecule of Candida species, it has antifungal activity at supraphysiological concentrations. Here, we studied the effect of tyrosol on the physiology and genome-wide transcription of Aspergillus nidulans to gain insight into the background of the antifungal activity of this compound. Tyrosol efficiently reduced germination of conidia and the growth on various carbon sources at a concentration of 35 mM. The growth inhibition was fungistatic rather than fungicide on glucose and was accompanied with downregulation of 2199 genes related to e.g. mitotic cell cycle, glycolysis, nitrate and sulphate assimilation, chitin biosynthesis, and upregulation of 2250 genes involved in e.g. lipid catabolism, amino acid degradation and lactose utilization. Tyrosol treatment also upregulated genes encoding glutathione-S-transferases (GSTs), increased specific GST activities and the glutathione (GSH) content of the cells, suggesting that A. nidulans can detoxify tyrosol in a GSH-dependent manner even though this process was weak. Tyrosol did not induce oxidative stress in this species, but upregulated "response to nutrient levels", "regulation of nitrogen utilization", "carbon catabolite activation of transcription" and "autophagy" genes. Tyrosol may have disturbed the regulation and orchestration of cellular metabolism, leading to impaired use of nutrients, which resulted in growth reduction.
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Antifúngicos , Aspergillus nidulans , Álcool Feniletílico/análogos & derivados , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Transcriptoma , Glutationa/genética , Glutationa/metabolismo , Glutationa/farmacologia , Carbono/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
This study introduces a tyrosol-loaded niosome integrated into a chitosan-alginate scaffold (Nio-Tyro@CS-AL), employing advanced electrospinning and 3D printing techniques for wound healing applications. The niosomes, measuring 185.40 ± 6.40 nm with a polydispersity index of 0.168 ± 0.012, encapsulated tyrosol with an efficiency of 77.54 ± 1.25%. The scaffold's microsized porous structure (600-900 µm) enhances water absorption, promoting cell adhesion, migration, and proliferation. Mechanical property assessments revealed the scaffold's enhanced resilience, with niosomes increasing the compressive strength, modulus, and strain to failure, indicative of its suitability for wound healing. Controlled tyrosol release was demonstrated in vitro, essential for therapeutic efficacy. The scaffold exhibited significant antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus, with substantial biofilm inhibition and downregulation of bacterial genes (ndvb and icab). A wound healing assay highlighted a notable increase in MMP-2 and MMP-9 mRNA expression and the wound closure area (69.35 ± 2.21%) in HFF cells treated with Nio-Tyro@CS-AL. In vivo studies in mice confirmed the scaffold's biocompatibility, showing no significant inflammatory response, hypertrophic scarring, or foreign body reaction. Histological evaluations revealed increased fibroblast and macrophage activity, enhanced re-epithelialization, and angiogenesis in wounds treated with Nio-Tyro@CS-AL, indicating effective tissue integration and repair. Overall, the Nio-Tyro@CS-AL scaffold presents a significant advancement in wound-healing materials, combining antibacterial properties with enhanced tissue regeneration, and holds promising potential for clinical applications in wound management.
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Quitosana , Álcool Feniletílico/análogos & derivados , Camundongos , Animais , Quitosana/farmacologia , Quitosana/química , Lipossomos , Alginatos/farmacologia , Alginatos/química , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Impressão TridimensionalRESUMO
BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial. METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9). RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation. CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.
Assuntos
Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Lactobacillus plantarum , Álcool Feniletílico/análogos & derivados , Simbióticos , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Azeite de Oliva , NF-kappa B , Ocludina , Modelos Animais de Doenças , Colite/induzido quimicamente , Inflamação/complicações , Inflamação/tratamento farmacológico , Colo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BLRESUMO
We studied the efficacy of different formulations of polyphenol extracts (mainly containing hydroxytyrosol and tyrosol) from olive mill vegetation water on the microflora on the surfaces of game meat cuts with high or low initial bacterial loads. Meat with a high microbial load (>5 Log cfu/g; mean value = 6.83 ± 0.45 standard deviation) was immersed for 10 or 60 sec into 25% and 10% solutions of microencapsulated freeze-dried and non-encapsulated polyphenolic extracts. Aerobic colony, Enterobacteriaceae, Pseudomonas spp., and lactic acid bacteria counts were determined on treated samples compared to controls after 7 days of storage (in vacuum-packed conditions at +3 °C). Significant differences were registered only for aerobic colony count for a 10% liquid extract treatment (0.64 log reduction). In contrast, the dipping or immersion of game meat with low initial microbial loads (<5 Log cfu/g; mean value = 3.58 ± 0.72 standard deviation) in 10% solutions of the polyphenol extracts effectuated significant reductions in all bacteria counts (p < 0.002) at 7 and 14 days of storage for different extracts, independently from the application methods. The use of the extracts to inhibit bacterial growth in game meat should only be considered if a good hygienic baseline is guaranteed.
RESUMO
Understanding fungal community dynamics during fermentation is important for assessing their influence on wine's phenolic content. The present study represents the first effort to explore the correlation between the autochthonous mycobiota of Marastina grapes collected from Dalmatian winegrowing sub-regions in Croatia and the phenolic composition, as well as the physicochemical parameters of wines produced through spontaneous fermentation. The metataxonomic approach revealed Metschnikowia pulcherrima, Metschnikowia fructicola and Hanseniaspora uvarum as the core mycobiota detected at the initial phase of fermentation. By contrast, Saccharomyces cerevisiae took over the dominance starting from the middle stage of fermentation. The wine's phenolic compounds were revealed by high-performance liquid chromatography, with tyrosol being the most abundant. Rhodotorula babjevae and Botrytis cinerea showed a positive correlation with p-hydroxybenzoic acid, gentisic acid, caffeic acid and cinnamic acid, while demonstrating a negative correlation with protocatechuic acid and chlorogenic acid. Heterophoma novae-verbascicola exhibited the opposite behaviour regarding the same phenolic compounds. The concentration of lactic acid was positively correlated with B. cinerea and negatively correlated with Het. novae-verbascicola. These findings serve as a foundation for in-depth investigations into the role of autochthonous grape mycobiota in phenolic transformation during spontaneous fermentation, potentially leading to the production of high-quality wines with unique terroir characteristics. Future studies should aim to explore the specific role played by individual yeast isolates in the formation of phenolic compounds.