RESUMEN
Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.
Asunto(s)
Antineoplásicos , Neoplasias del Colon , Ajo , Plantas Medicinales , Masculino , Humanos , Extractos Vegetales/química , Estudios Prospectivos , Ácidos Sulfínicos/química , Disulfuros , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Ajo/químicaRESUMEN
Garlic has been used worldwide as a spice due to its pungent taste and flavor-enhancing properties. As a main biologically active component of the freshly crushed garlic extracts, allicin (diallyl thiosulfinate) is converted from alliin by alliinase upon damaging the garlic clove, which has been reported to have many potent beneficial biological functions. In this work, allicin formation, stability, bioavailability, and metabolism process are examined and summarized. The biological functions of allicin and potential underlying mechanisms are reviewed and discussed, including antioxidation, anti-inflammation, antidiabetic, cardioprotective, antineurodegenerative, antitumor, and antiobesity effects. Novel delivery systems of allicin with enhanced stability, encapsulation efficiency, and bioavailability are also evaluated, such as nanoparticles, gels, liposomes, and micelles. This study could provide a comprehensive understanding of the physiochemical properties and health benefits of allicin, with great potential for further applications in the food and nutraceutical industries.
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Disulfuros , Ajo , Disponibilidad Biológica , Suplementos Dietéticos , Ajo/química , Ácidos Sulfínicos/química , Antioxidantes/metabolismoRESUMEN
Garlic, Allium sativum, has long been utilized for a number of medicinal purposes around the world, and its medical benefits have been well documented. The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. Garlic and garlic extracts, especially aged garlic extracts (AGEs), are rich in bioactive compounds, with potent anti-inflammatory, antioxidant and neuroprotective activities. In light of these effects, garlic and its components have been examined in experimental models of Alzheimer's disease (AD), the most common form of dementia without therapy, and a growing health concern in aging societies. With the aim of offering an updated overview, this paper reviews the chemical composition, metabolism and bioavailability of garlic bioactive compounds. In addition, it provides an overview of signaling mechanisms triggered by garlic derivatives, with a focus on allicin and AGE, to improve learning and memory.
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Enfermedad de Alzheimer , Productos Biológicos , Ajo , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Disulfuros , Ajo/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Fungal infections of the lung are an increasing problem worldwide and the search for novel therapeutic agents is a current challenge due to emerging resistance to current antimycotics. The volatile defence substance allicin is formed naturally by freshly injured garlic plants and exhibits broad antimicrobial potency. Chemically synthesised allicin was active against selected fungi upon direct contact and via the gas phase at comparable concentrations to the pharmaceutically used antimycotic amphotericin B. We investigated the suppression of fungal growth by allicin vapour and aerosols in vitro in a test rig at air flow conditions mimicking the human lung. The effect of allicin via the gas phase was enhanced by ethanol. Our results suggest that allicin is a potential candidate for development for use in antifungal therapy for lung and upper respiratory tract infections.
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Micosis , Ácidos Sulfínicos , Disulfuros , Humanos , Pulmón , Micosis/tratamiento farmacológico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
Phytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product.
Asunto(s)
Productos Biológicos , Ajo , Neoplasias , Disulfuros/uso terapéutico , Ajo/química , Humanos , Neoplasias/tratamiento farmacológico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Ácidos Sulfínicos/uso terapéuticoRESUMEN
The volatile organic sulfur compound allicin (diallyl thiosulfinate) is produced as a defense substance when garlic (Allium sativum) tissues are damaged, for example by the activities of pathogens or pests. Allicin gives crushed garlic its characteristic odor, is membrane permeable and readily taken up by exposed cells. It is a reactive thiol-trapping sulfur compound that S-thioallylates accessible cysteine residues in proteins and low molecular weight thiols including the cellular redox buffer glutathione (GSH) in eukaryotes and Gram-negative bacteria, as well as bacillithiol (BSH) in Gram-positive firmicutes. Allicin shows dose-dependent antimicrobial activity. At higher doses in eukaryotes allicin can induce apoptosis or necrosis, whereas lower, biocompatible amounts can modulate the activity of redox-sensitive proteins and affect cellular signaling. This review summarizes our current knowledge of how bacterial and eukaryotic cells are specifically affected by, and respond to, allicin.
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Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/farmacología , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Disulfuros , Ajo/química , Ajo/metabolismo , Glutatión/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Compuestos de Sulfhidrilo/metabolismoRESUMEN
Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its analogues, e.g., pulmonary drug delivery, treatment of superficial injuries, or urease inhibitors in fertilizers. Here, we discuss the effect of temperature, pH, buffers, salts, and additives, i.e. antioxidants, chelating agents, reducing agents and cosolvents, on the stability and the activity of alliinase extracted from garlic. The effects of the storage temperature and relative humidity on the stability of lyophilized alliinase was demonstrated. A combination of the short half-life, high reactivity and non-specificity to particular proteins are reasons most bacteria cannot deal with allicin's mode of action and develop effective defence mechanism, which could be the key to sustainable drug design addressing serious problems with escalating emergence of multidrug-resistant (MDR) bacterial strains.
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Liasas de Carbono-Azufre/metabolismo , Fenómenos Químicos , Disulfuros/metabolismo , Ajo/enzimología , Ácidos Sulfínicos/metabolismo , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/ultraestructura , Biocatálisis/efectos de los fármacos , Tampones (Química) , Disulfuros/química , Estabilidad de Enzimas/efectos de los fármacos , Liofilización , Concentración de Iones de Hidrógeno , Cinética , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Estereoisomerismo , Ácidos Sulfínicos/química , Temperatura , Factores de TiempoRESUMEN
Medicinal plants have been used from ancient times for human healthcare as in the form of traditional medicines, spices, and other food components. Garlic (Allium sativum L.) is an aromatic herbaceous plant that is consumed worldwide as food and traditional remedy for various diseases. It has been reported to possess several biological properties including anticarcinogenic, antioxidant, antidiabetic, renoprotective, anti-atherosclerotic, antibacterial, antifungal, and antihypertensive activities in traditional medicines. A. sativum is rich in several sulfur-containing phytoconstituents such as alliin, allicin, ajoenes, vinyldithiins, and flavonoids such as quercetin. Extracts and isolated compounds of A. sativum have been evaluated for various biological activities including antibacterial, antiviral, antifungal, antiprotozoal, antioxidant, anti-inflammatory, and anticancer activities among others. This review examines the phytochemical composition, pharmacokinetics, and pharmacological activities of A. sativum extracts as well as its main active constituent, allicin.
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Ajo/química , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Productos Biológicos/química , Productos Biológicos/farmacología , Disulfuros , Estabilidad de Medicamentos , Humanos , Fitoquímicos/farmacocinética , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacocinética , Extractos Vegetales/uso terapéutico , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacologíaRESUMEN
Phenotypic screening in disease-relevant models identifies small molecule hits with desirable efficacy but often with unknown modes of action. Target identification and validation are integral to successful biomedical research. Technologies are required to validate the biological target (or targets) through which a pharmacological agent is proposed to exert its effects. This work details the rational structure-based design, synthetic preparation and cell-based application of a clickable sulfonyl fluoride chemical probe to directly report on the mechanism of a series of compounds previously discovered in a reporter gene assay. Quantification of drug-target occupancy in living human primary cells enabled a deeper understanding of the molecular pharmacology of the chemotype. The technology described herein should be of broad interest to those involved in chemical biology research and the drug discovery endeavor.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Ácidos Sulfínicos/química , Células Cultivadas , Química Clic/métodos , Descubrimiento de Drogas/métodos , Endorribonucleasas/antagonistas & inhibidores , Endorribonucleasas/química , Inhibidores Enzimáticos/farmacología , Humanos , Modelos Moleculares , Ácidos Sulfínicos/síntesis químicaRESUMEN
BACKGROUND: Cancer is a multi-factorial disease including alterations in the cell signalling pathways. Currently, several drugs are in use to treat cancer but such drugs show negative side effects on normal cells and cause severe toxicity. METHODS: The current research is mainly focused on medicinal plants with potential therapeutic efficacy in the treatment of cancer without any adverse effects on normal cells. In this regard, garlic and its active compounds including diallyl sulfide, diallyl trisulfide, ajoene, and allicin have been established to suppress the growth of cancer and killing of cancer cells. RESULT: The review focuses on garlic and its active compounds chemopreventive effect through modulating various cell signalling pathways. Additionally, garlic and its active compound were established to induce cell cycle arrest at the G0/G1 phase and G2/M phases in cancer cells, increase the expression of tumor suppressor genes, inhibit the angiogenesis process, induction of apoptosis and modulation of various other genetic pathways. CONCLUSION: This review sketches the diverse chemopreventive activities of garlic and their active ingredients in the management of cancer mainly focusing on cell signalling pathways.
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Compuestos Alílicos/farmacología , Disulfuros/farmacología , Ajo/química , Neoplasias/prevención & control , Plantas Medicinales/química , Transducción de Señal/efectos de los fármacos , Sulfuros/farmacología , Ácidos Sulfínicos/farmacología , Compuestos Alílicos/química , Proliferación Celular/efectos de los fármacos , Disulfuros/química , Humanos , Neoplasias/patología , Sulfuros/química , Ácidos Sulfínicos/química , SulfóxidosRESUMEN
This study investigates the effects of catalytic infrared (CIR) dry-blanching (CIRDB) on the processing and quality of garlic slices. CIRDB processing parameters of CIR processing temperature, slice thickness and processing time were studied versus the processing characteristics of internal temperature, peroxidase (POD) activity and moisture reduction. Blanched garlic quality characteristics of surface color change (ΔE), allicin retention rate, vitamin C retention rate and microbial content were determined. Hot water blanching (WB) was used as a comparison. The results indicated that increasing CIR processing temperature and/or reducing the slice thickness accelerated internal temperature rise and POD inactivation and moisture reduction. To achieve 90% inactivation of POD, the CIRDB treatment resulted in moisture reductions of 15.87-40.37%, microbial reductions of 1.76-3.91-log, ΔE between 2.03 and 10.01, retention rate of allicin between 10.63 and 33.31%, and retention rate of vitamin C between 55.00 and 81.13%. CIRDB achieved the high-quality garlic products compared with WB.
Asunto(s)
Ajo/química , Rayos Infrarrojos , Ácido Ascórbico/química , Bacterias/efectos de la radiación , Color , Culinaria , Disulfuros , Ajo/metabolismo , Peroxidasa/metabolismo , Ácidos Sulfínicos/química , Temperatura , Agua/químicaRESUMEN
Bald's eyesalve is an Anglo-Saxon medicinal remedy that has been used through ancient times to treat eye sty infections and may represent a source of ancientbiotics. This study assessed the efficacy of Bald's eyesalve against several strains of Staphylococcus aureus and Pseudomonas aeruginosa, including a multi-drug resistant phenotype, and identified the principal compound conveying antibacterial activity. Bald's eyesalve formulations were produced by combining garlic, onion or leek, wine, bovine bile, and brass, with specific ingredient omissions in several formulations, followed by incubation at 4 °C for 9 days. Bald's eyesalve formulation ES-GBBr exhibited the greatest antibacterial activity against S. aureus and P. aeruginosa. Fractionation of ES-GBBr using molecular size exclusion and organic solvent partitioning isolated its antibacterial activity to the small molecule nonpolar fraction, and 1D 1H NMR revealed the identity of the antibacterial agent to be allicin. Depletion of allicin from this fraction by addition of exogenous cysteine established that all observable growth inhibition originated from allicin. Quantification of allicin demonstrated that its concentration was significantly greater in ES-GBBr compared to the ES-O formulation; however, this was not due to greater yield. The antibacterial activity of allicin against S. aureus was antagonized by other ingredients within Bald's eyesalve, whereas they were additive or synergistic against P. aeruginosa. These results suggest that neither leek nor onion is necessary for the antibacterial efficacy of Bald's eyesalve against S. aureus or P. aeruginosa, and while allicin was identified as the principal antibacterial agent present, its activity is influenced differentially in the presence of additional Bald's eyesalve ingredients when used against S. aureus compared to P. aeruginosa. Ancientbiotics may provide a source of promising antibacterials; however, identifying the source of activity and assessing distinct formulations for cooperative effects are essential to using ancient remedies, such as Bald's eyesalve, effectively against drug resistant pathogens.
Asunto(s)
Antibacterianos/farmacología , Medicina Tradicional , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pomadas/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Antibacterianos/química , Bilis , Bovinos , Cobre , Disulfuros , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana , Ajo , Pruebas de Sensibilidad Microbiana , Pomadas/química , Cebollas , Ácidos Sulfínicos/química , Ácidos Sulfínicos/farmacología , Vino , ZincRESUMEN
We describe a short total synthesis of ajoene, a major biologically active constituent of garlic. The instability of allicin as the only other known alternative starting material has led to the development of a reliable procedure for the synthesis of ajoene from simple building blocks that is also suitable for upscale operations.
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Disulfuros/química , Disulfuros/síntesis química , Disulfuros/farmacología , Ajo/química , Ajo/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Percepción de Quorum/efectos de los fármacos , Selenio/química , Ácidos Sulfínicos/química , SulfóxidosRESUMEN
This work addresses the need for chemical tools that can selectively form cross-links. Contemporary thiol-selective cross-linkers, for example, modify all accessible thiols, but only form cross-links between a subset. The resulting terminal "dead-end" modifications of lone thiols are toxic, confound cross-linking-based studies of macromolecular structure, and are an undesired, and currently unavoidable, byproduct in polymer synthesis. Using the thiol pair of Cu/Zn-superoxide dismutase (SOD1), we demonstrated that cyclic disulfides, including the drug/nutritional supplement lipoic acid, efficiently cross-linked thiol pairs but avoided dead-end modifications. Thiolate-directed nucleophilic attack upon the cyclic disulfide resulted in thiol-disulfide exchange and ring cleavage. The resulting disulfide-tethered terminal thiolate moiety either directed the reverse reaction, releasing the cyclic disulfide, or participated in oxidative disulfide (cross-link) formation. We hypothesized, and confirmed with density functional theory (DFT) calculations, that mono- S-oxo derivatives of cyclic disulfides formed a terminal sulfenic acid upon ring cleavage that obviated the previously rate-limiting step, thiol oxidation, and accelerated the new rate-determining step, ring cleavage. Our calculations suggest that the origin of accelerated ring cleavage is improved frontier molecular orbital overlap in the thiolate-disulfide interchange transition. Five- to seven-membered cyclic thiosulfinates were synthesized and efficiently cross-linked up to 104-fold faster than their cyclic disulfide precursors; functioned in the presence of biological concentrations of glutathione; and acted as cell-permeable, potent, tolerable, intracellular cross-linkers. This new class of thiol cross-linkers exhibited click-like attributes including, high yields driven by the enthalpies of disulfide and water formation, orthogonality with common functional groups, water-compatibility, and ring strain-dependence.
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Reactivos de Enlaces Cruzados/química , Disulfuros/química , Compuestos de Sulfhidrilo/química , Ácidos Sulfínicos/química , Superóxido Dismutasa-1/química , Línea Celular Tumoral , Reactivos de Enlaces Cruzados/síntesis química , Disulfuros/síntesis química , Humanos , Modelos Químicos , Oxidación-Reducción , Teoría Cuántica , Ácidos Sulfénicos/química , Ácidos Sulfínicos/síntesis químicaRESUMEN
Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with broad antimicrobial activities in the low µM range against Gram-positive and -negative bacteria, including antibiotic resistant strains, and fungi. Allicin reacts with thiol groups and can inactivate essential enzymes. However, allicin is unstable at room temperature and antimicrobial activity is lost within minutes upon heating to >80 °C. Allicin's antimicrobial activity is due to the thiosulfinate group, so we synthesized a series of allicin analogues and tested their antimicrobial properties and thermal stability. Dimethyl-, diethyl-, diallyl-, dipropyl- and dibenzyl-thiosulfinates were synthesized and tested in vitro against bacteria and the model fungus Saccharomyces cerevisiae, human and plant cells in culture and Arabidopsis root growth. The more volatile compounds showed significant antimicrobial properties via the gas phase. A chemogenetic screen with selected yeast mutants showed that the mode of action of the analogues was similar to that of allicin and that the glutathione pool and glutathione metabolism were of central importance for resistance against them. Thiosulfinates differed in their effectivity against specific organisms and some were thermally more stable than allicin. These analogues could be suitable for applications in medicine and agriculture either singly or in combination with other antimicrobials.
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Arabidopsis/efectos de los fármacos , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Ácidos Sulfínicos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Arabidopsis/crecimiento & desarrollo , Arabidopsis/microbiología , Bacterias/patogenicidad , Disulfuros , Hongos/patogenicidad , Ajo/química , Glutatión/metabolismo , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/farmacología , Ácidos Sulfínicos/química , Ácidos Tiosulfónicos/química , Ácidos Tiosulfónicos/farmacologíaRESUMEN
A unique category of basic side chain containing amino acid derived sulfonyl fluorides (SFs) has been synthesized for incorporation into new proteasome inhibitors targeting the trypsin-like site of the 20S proteasome. Masking the former α-amino functionality of the amino acid starting derivatives as an azido functionality allowed an elegant conversion to the corresponding amino acid derived sulfonyl fluorides. The inclusion of different SFs at the P1 site of a proteasome inhibitor resulted in 14 different peptidosulfonyl fluorides (PSFs) having a high potency and an excellent selectivity for the proteolytic activity of the ß2 subunit over that of the ß5 subunit. The results of this study strongly indicate that a free N-terminus of PSFs inhibitors is crucial for high selectivity toward the trypsin-like site of the 20S proteasome. Nevertheless, all compounds are slightly more selective for inhibition of the constitutive over the immunoproteasome.
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Aminoácidos/química , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/química , Inhibidores de Proteasoma/farmacología , Ácidos Sulfínicos/química , Evaluación Preclínica de Medicamentos/métodos , Humanos , Complejo de la Endopetidasa Proteasomal/química , Relación Estructura-Actividad , Tripsina/química , Tripsina/metabolismoRESUMEN
BACKGROUND: Allicin and soluble solid content (SSC) in garlic is the responsible for its pungent flavor and odor. However, current conventional methods such as the use of high-pressure liquid chromatography and a refractometer have critical drawbacks in that they are time-consuming, labor-intensive and destructive procedures. The present study aimed to predict allicin and SSC in garlic using hyperspectral imaging in combination with variable selection algorithms and calibration models. RESULTS: Hyperspectral images of 100 garlic cloves were acquired that covered two spectral ranges, from which the mean spectra of each clove were extracted. The calibration models included partial least squares (PLS) and least squares-support vector machine (LS-SVM) regression, as well as different spectral pre-processing techniques, from which the highest performing spectral preprocessing technique and spectral range were selected. Then, variable selection methods, such as regression coefficients, variable importance in projection (VIP) and the successive projections algorithm (SPA), were evaluated for the selection of effective wavelengths (EWs). Furthermore, PLS and LS-SVM regression methods were applied to quantitatively predict the quality attributes of garlic using the selected EWs. Of the established models, the SPA-LS-SVM model obtained an Rpred2 of 0.90 and standard error of prediction (SEP) of 1.01% for SSC prediction, whereas the VIP-LS-SVM model produced the best result with an Rpred2 of 0.83 and SEP of 0.19 mg g-1 for allicin prediction in the range 1000-1700 nm. Furthermore, chemical images of garlic were developed using the best predictive model to facilitate visualization of the spatial distributions of allicin and SSC. CONCLUSION: The present study clearly demonstrates that hyperspectral imaging combined with an appropriate chemometrics method can potentially be employed as a fast, non-invasive method to predict the allicin and SSC in garlic. © 2018 Society of Chemical Industry.
Asunto(s)
Técnicas de Química Analítica/métodos , Ajo/química , Análisis Espectral/métodos , Ácidos Sulfínicos/química , Algoritmos , Calibración , Disulfuros , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Máquina de Vectores de SoporteRESUMEN
Complexes of amylose (Am) with garlic bioactive components (GBCs) were prepared by milling activating treatment of Am and garlic paste (GP) together. The complex, produced by milling for 2.5h with the garlic (dry basis)/Am ratio of 1:5 (w/w) and water content of 25% (w/w) exhibited significantly higher allicin content (0.49mg/g of complex) than others. The scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), high performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS) techniques were used complex characterization. XRD results indicated that the Am and garlic bioactive components formed the V-type structure. FT-IR and DSC analysis further confirmed the formation of the Am-GBCs complex, and its thermal stability was improved in comparison with garlic powder. According to GC-MS results, all organosulfur compounds (OSCs) in fresh garlic were better retained to Am-GBCs complex. Therefore, the Am-GBCs complexes can have important applications as stable natural flavor compound systems.
Asunto(s)
Amilosa/química , Manipulación de Alimentos/métodos , Ajo/química , Ácidos Sulfínicos/química , Rastreo Diferencial de Calorimetría , Cromatografía Líquida de Alta Presión , Disulfuros , Cromatografía de Gases y Espectrometría de Masas , Microscopía Electrónica de Rastreo , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría , Factores de Tiempo , Agua/química , Difracción de Rayos XRESUMEN
Garlic (Allium sativum) has potent antimicrobial activity due to allicin (diallylthiosulfinate) synthesized by enzyme catalysis in damaged garlic tissues. Allicin gives crushed garlic its characteristic odor and its volatility makes it potentially useful for combating lung infections. Allicin was synthesized (>98% pure) by oxidation of diallyl disulfide by H2O2 using formic acid as a catalyst and the growth inhibitory effect of allicin vapor and allicin in solution to clinical isolates of lung pathogenic bacteria from the genera Pseudomonas, Streptococcus, and Staphylococcus, including multi-drug resistant (MDR) strains, was demonstrated. Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were determined and compared to clinical antibiotics using standard European Committee on Antimicrobial Susceptibility Testing (EUCAST) procedures. The cytotoxicity of allicin to human lung and colon epithelial and murine fibroblast cells was tested in vitro and shown to be ameliorated by glutathione (GSH). Similarly, the sensitivity of rat precision-cut lung slices (PCLS) to allicin was decreased by raising the [GSH] to the approximate blood plasma level of 1 mM. Because allicin inhibited bacterial growth as a vapor, it could be used to combat bacterial lung infections via direct inhalation. Since there are no volatile antibiotics available to treat pulmonary infections, allicin, particularly at sublethal doses in combination with oral antibiotics, could make a valuable addition to currently available treatments.
Asunto(s)
Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Ajo/química , Ácidos Sulfínicos/farmacología , Compuestos Orgánicos Volátiles/farmacología , Animales , Antiinfecciosos/química , Línea Celular , Disulfuros , Humanos , Pulmón/microbiología , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Ratas , Streptococcus pneumoniae/efectos de los fármacos , Ácidos Sulfínicos/química , Compuestos Orgánicos Volátiles/químicaRESUMEN
Organosulfur compounds derived from Allium vegetables have long been recognized for various therapeutic effects, including anticancer activity. Allicin, one of the main biologically active components of garlic, shows promise as an anticancer agent; however, instability makes it unsuitable for clinical application. The aim of this study was to investigate the effect of stabilized allicin derivatives on human breast cancer cells in vitro. In this study, a total of 22 stabilized thiosulfinate derivatives were synthesized and screened for their in vitro antiproliferative activities against drug-sensitive (MCF-7) and multidrug-resistant (MCF-7/Dx) human adenocarcinoma breast cancer cells. Assays for cell death, apoptosis, cell cycle progression and mitochondrial bioenergetic function were performed. Seven compounds (4b, 7b, 8b, 13b, 14b, 15b and 18b) showed greater antiproliferative activity against MCF-7/Dx cells than allicin. These compounds were also selective towards multidrug-resistant (MDR) cells, a consequence attributed to collateral sensitivity. Among them, 13b exhibited the greatest anticancer activity in both MCF-7/Dx and MCF-7 cells, with IC50 values of 18.54±0.24 and 46.50±1.98 µmol/L, respectively. 13b altered cellular morphology and arrested the cell cycle at the G2/M phase. Additionally, 13b dose-dependently induced apoptosis, and inhibited cellular mitochondrial respiration in cells at rest and under stress. MDR presents a significant obstacle to the successful treatment of cancer clinically. These results demonstrate that thiosulfinate derivatives have potential as novel anticancer agents and may offer new therapeutic strategies for the treatment of chemoresistant cancers.