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Pseudomonas aeruginosa is widely associated with biofilm-mediated antibiotic resistant chronic and acute infections which constitute a persistent healthcare challenges. Addressing this threat requires exploration of novel therapeutic strategies involving the combination of natural compounds and conventional antibiotics. Hence, our study has focused on two compounds; cuminaldehyde and ciprofloxacin, which were strategically combined to target the biofilm challenge of P. aeruginosa. The minimum inhibitory concentration (MIC) of cuminaldehyde and ciprofloxacin was found to be 400 µg/mL and 0.4 µg/mL, respectively. Moreover, the fractional inhibitory concentration index (FICI = 0.62) indicated an additive interaction prevailed between cuminaldehyde and ciprofloxacin. Subsequently, sub-MIC doses of cuminaldehyde (25 µg/mL) and ciprofloxacin (0.05 µg/mL) were selected for an array of antibiofilm assays which confirmed their biofilm inhibitory potential without exhibiting any antimicrobial activity. Furthermore, selected doses of the mentioned compounds could manage biofilm on catheter surface by inhibiting and disintegrating existing biofilm. Additionally, the test combination of the mentioned compounds reduced virulence factors secretion, accumulated reactive oxygen species and increased cell-membrane permeability. Thus, the combination of cuminaldehyde and ciprofloxacin demonstrates potential in combating biofilm-associated Pseudomonal threats.
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Antibacterianos , Benzaldeídos , Biofilmes , Ciprofloxacina , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Espécies Reativas de Oxigênio , Biofilmes/efeitos dos fármacos , Ciprofloxacina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Antibacterianos/farmacologia , Benzaldeídos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Virulência , Cimenos/farmacologia , Sinergismo Farmacológico , Permeabilidade da Membrana Celular/efeitos dos fármacos , HumanosRESUMO
Cuminum cyminum L. is a versatile spice belonging to family Apiaceae. Though the plant has pan-tropical distribution but it is indigenous to Egypt, the Mediterranean, and South Asian countries. It exhibits numerous culinary, traditional, and pharmacological attributes. Its traditional uses also validate its immense pharmacological potential. Cuminum cyminum is the hub of numerous bioactives such as alkaloids, flavonoids, terpenoids, and so forth. Cuminaldehyde is the major bioactive, rendered to most of its pharmacological as well as clinical significance. The present study comprised of current knowledge on its taxonomy, nutritional, traditional, phytochemistry, pharmacology (antimicrobial, antioxidant, anti-inflammation, antidiabetic, wound healing, anticancer, etc.), toxicology, and clinical attributes. Besides, the mechanism of action is also well explained. The present study provides a rationale for further bioprospection of this wonder plant. Future studies are needed to fill the research gaps, particularly on relevant phytocompound isolation, their pre-clinical and clinical characterization, evaluation, and structure-activity relationship. Moreover, well-designed and highly appropriate clinical and placebo trials are still needed to demonstrate the trustworthy role of cumin on human health.
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Cuminum , Compostos Fitoquímicos/farmacologia , Cuminum/química , Humanos , Extratos Vegetais/farmacologia , Especiarias/análiseRESUMO
Urease is an enzyme that plays a significant role in the hydrolysis of urea into carbonic acid and ammonia via the carbamic acid formation. The resultant increase in pH leads to the onset of various pathologies such as gastric cancer, urolithiasis, hepatic coma, hepatic encephalopathy, duodenal ulcers and peptic ulcers. Urease inhibitors can reduce the urea hydrolysis rate and development of various diseases. The Cinnamomum genus is used in a large number of traditional medicines. It is well established that stem bark of Cinnamomum cassia exhibits antiulcerogenic potential. The present study evaluated the inhibitory effect of seven extracts of Cinnamomum camphora, Cinnamomum verum and two pure compounds Camphene and Cuminaldehyde on urease enzyme. Kinetic studies of potential inhibitors were carried out. Methanol extract (IC50 980 µg/mL) of C. camphora and a monoterpene Camphene (IC50 0.147 µg/mL) possess significant inhibitory activity. The Lineweaver Burk plot analysis suggested the competitive inhibition by methanol extract, hexane fraction and Camphene. The Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of hexane fraction revealed the contribution of various terpenes. The present study targets terpenes as a new class of inhibitors that have potential therapeutic value for further development as novel drugs.
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Proteínas de Bactérias , Cinnamomum/química , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Urease , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Urease/antagonistas & inibidores , Urease/químicaRESUMO
Vancomycin-resistant Enterococcus faecium (VRE) has become endemic in healthcare settings, reducing treatment options for enterococcal infections. New antimicrobials for VRE infections are a high priority, but the development of novel antibiotics is time-consuming and expensive. Essential oils (EOs) synergistically enhance the activity of some existing antibiotics, suggesting that EO-antibiotic combinations could resensitise resistant bacteria and maintain the antibiotic repertoire. The mechanism of resensitisation of bacteria to antibiotics by EOs is relatively understudied. Here, the synergistic interactions between carvacrol (1.98 mM) and cuminaldehyde (4.20 mM) were shown to reestablish susceptibility to vancomycin (0.031 mg/L) in VRE, resulting in bactericidal activity (4.73 log10 CFU/ml reduction). Gene expression profiling, coupled with ß-galactosidase leakage and salt tolerance assays, suggested that cell envelope damage contributes to the synergistic bactericidal effect against VRE. The EO-vancomycin combination was also shown to kill clinical isolates of VRE (2.33-5.25 log10 CFU/ml reduction), and stable resistance did not appear to develop even after multiple passages. The in vivo efficacy of the EO-vancomycin combination was tested in a Galleria mellonella larvae assay; however, no antimicrobial action was observed, indicating that further drug development is required for the EO-vancomycin combination to be clinically useful for treatment of VRE infections.
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Antibacterianos/uso terapêutico , Benzaldeídos/uso terapêutico , Cimenos/uso terapêutico , Enterococcus faecalis/efeitos dos fármacos , Vancomicina/uso terapêutico , Antibacterianos/farmacologia , Benzaldeídos/farmacologia , Cimenos/farmacologia , Enterococcus faecium/efeitos dos fármacos , Humanos , Vancomicina/farmacologiaRESUMO
Effect of cryogenic grinding on recovery of volatile oil, fatty oil percentage and their constituents in two cumin (Cuminum cyminum L.) genotypes have been analyzed. Cryogenic grinding not only retains the volatiles but enhanced the recovery by 33.9 % in GC 4 and 43.5 % in RZ 209. A significant increase (29.9 %) over normal grinding in oil percentage was also observed in genotype RZ 209. This increase was, however, less (15.4 %) in genotype GC 4. Nineteen major compounds were identified in the essential oil of both genotypes. The two grinding techniques had significant effects on dependent variables, viz., volatile oil and monoterpenes. Cuminaldehyde was the main constituent in both genotypes, content of which increased from 48.2 to 56.1 % in GC 4 on cryo grinding. Content of terpines were found to decrease in cryo ground samples of GC 4 and either decrease or no change was found in RZ 209. Organoleptic test showed more pleasant aroma in cryo ground seeds of both the genotypes. Significant increase was also reported in fatty oil yield due to cryogenic grinding. Fatty acid methyl ester (FAME) analysis showed oleic acid as major FAME content of which increased from 88.1 to 94.9 % in RZ 209 and from 88.2 to 90.1 % in GC 4 on cryogenic grinding. Other prominent FAME were palmitic, palmitoleic and stearic acid. Results indicated commercial potential of cryogenic grinding technology for cumin in general and spices in particular for better retention of flavour and quality in spices.
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The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections. Thus, P. aeruginosa has been treated with cuminaldehyde (a naturally occurring phytochemical) and gentamicin (an aminoglycoside antibiotic) in connection to the effective management of the biofilm challenges. It was also observed that the test molecules could show increased antimicrobial activity against P. aeruginosa. A fractional inhibitory concentration index (FICI) of 0.65 suggested an additive interaction between cuminaldehyde and gentamicin. Besides, a series of experiments such as crystal violet assay, estimation of extracellular polymeric substance (EPS), and microscopic images indicated that an enhanced antibiofilm activity was obtained when the selected compounds were applied together on P. aeruginosa. Furthermore, the combination of the selected compounds was found to reduce the secretion of virulence factors from P. aeruginosa. Taken together, this study suggested that the combinatorial application of cuminaldehyde and gentamicin could be considered an effective approach towards the control of biofilm-linked infections caused by P. aeruginosa.
Assuntos
Antibacterianos , Benzaldeídos , Biofilmes , Gentamicinas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Gentamicinas/farmacologia , Antibacterianos/farmacologia , Benzaldeídos/farmacologia , Cimenos/farmacologia , Fatores de Virulência , Sinergismo Farmacológico , HumanosRESUMO
Staphylococcus aureus, an opportunistic Gram-positive pathogen, is known for causing various infections in humans, primarily by forming biofilms. The biofilm-induced antibiotic resistance has been considered a significant medical threat. Combinatorial therapy has been considered a reliable approach to combat antibiotic resistance by using multiple antimicrobial agents simultaneously, targeting bacteria through different mechanisms of action. To this end, we examined the effects of two molecules, cuminaldehyde (a natural compound) and tobramycin (an antibiotic), individually and in combination, against staphylococcal biofilm. Our experimental observations demonstrated that cuminaldehyde (20 µg/mL) in combination with tobramycin (0.05 µg/mL) exhibited efficient reduction in biofilm formation compared to their individual treatments (p < 0.01). Additionally, the combination showed an additive interaction (fractional inhibitory concentration value 0.66) against S. aureus. Further analysis revealed that the effective combination accelerated the buildup of reactive oxygen species (ROS) and increased the membrane permeability of the bacteria. Our findings also specified that the cuminaldehyde in combination with tobramycin efficiently reduced biofilm-associated pathogenicity factors of S. aureus, including fibrinogen clumping ability, hemolysis property, and staphyloxanthin production. The selected concentrations of tobramycin and cuminaldehyde demonstrated promising activity against the biofilm development of S. aureus on catheter models without exerting antimicrobial effects. In conclusion, the combination of tobramycin and cuminaldehyde presented a successful strategy for combating staphylococcal biofilm-related healthcare threats. This combinatorial approach holds the potential for controlling biofilm-associated infections caused by S. aureus.
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BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.
Assuntos
Antidiarreicos , Benzaldeídos , Cimenos , Parassimpatolíticos , Ratos , Camundongos , Animais , Antidiarreicos/efeitos adversos , Parassimpatolíticos/efeitos adversos , Cromakalim/efeitos adversos , Glibureto/efeitos adversos , Extratos Vegetais/farmacologia , Jejuno , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Verapamil/efeitos adversos , Trifosfato de AdenosinaRESUMO
Considering the COVID-19 pandemic, this research aims to investigate some herbs as probable therapies for this disease. Achillea millefolium (Yarrow), Alkanet, Rumex patientia (Patience dock), Dill, Tarragon, and sweet fennel, including some principal chemical compounds of achillin, alkannin, cuminaldehyde, dillapiole, estragole, and fenchone have been selected. The possible roles of these medicinal plants in COVID-19 treatment have been investigated through quantum sensing methods. The formation of hydrogen bonding between the principal substances selected in anti-COVID natural drugs and Tyr-Met-His (the database amino acids fragment), as the active area of the COVID protein, has been evaluated. The physical and chemical attributes of nuclear magnetic resonance, vibrational frequency, the highest occupied molecular orbital energy and the lowest unoccupied molecular orbital energy, partial charges, and spin density have been investigated using the DFT/TD-DFT method and 6-311+G (2d,p) basis set by the Gaussian 16 revision C.01 program toward the industry of drug design. This research has exhibited that there is relative agreement among the results that these medicinal plants could be efficient against COVID-19 symptoms.
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CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-Ò¡B, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.
Assuntos
Benzaldeídos , Benzoquinonas , Tetracloreto de Carbono , Ácido Gálico , Rim , Pulmão , NF-kappa B , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Animais , Ácido Gálico/farmacologia , Benzoquinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ratos , Tetracloreto de Carbono/toxicidade , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Benzaldeídos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Simulação de Acoplamento Molecular , Cimenos/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ratos Wistar , Ratos Sprague-DawleyRESUMO
Pseudomonas aeruginosa, an opportunistic pathogen, has been found to cause several chronic and acute infections in human. Moreover, it often shows drug-tolerance and poses a severe threat to public healthcare through biofilm formation. In this scenario, two molecules, namely, cuminaldehyde and tobramycin, were used separately and in combination for the efficient management of biofilm challenge. The minimum inhibitory concentration (MIC) of cuminaldehyde and tobramycin was found to be 150 µg/mL and 1 µg/mL, respectively, against Pseudomonas aeruginosa. The checkerboard assay revealed that the fractional inhibitory concentration (FIC) index of cuminaldehyde and tobramycin was 0.36 suggesting a synergistic association between them. The sub-MIC dose of cuminaldehyde (60 µg/mL) or tobramycin (0.06 µg/mL) individually did not show any effect on the microbial growth curve. However, the same combinations could affect microbial growth curve of Pseudomonas aeruginosa efficiently. In connection to biofilm management, it was observed that the synergistic interaction between cuminaldehyde and tobramycin could inhibit biofilm formation more efficiently than their single use (p < 0.01). Further investigation revealed that the combinations of cuminaldehyde and tobramycin could generate reactive oxygen species (ROS) that resulted in the increase of membrane permeability of bacterial cells leading to the efficient inhibition of microbial biofilm formation. Besides, the synergistic interaction between cuminaldehyde (20 µg/mL) and tobramycin (0.03 µg/mL) also showed significant biofilm dispersal of the test microorganism (p < 0.01). Hence, the results suggested that synergistic action of cuminaldehyde and tobramycin could be applied for the efficient management of microbial biofilm.
Assuntos
Infecções por Pseudomonas , Tobramicina , Humanos , Tobramicina/farmacologia , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Biofilmes , Testes de Sensibilidade Microbiana , Sinergismo FarmacológicoRESUMO
PURPOSE: Cuminaldehyde (CA), an oxidized aldehyde monoterpene, is a major essential oil component in cumin seeds, which has shown different promising medical effects. In this study, we comprehensively evaluated the antileishmanial potential of Bunium persicum (Boiss) B. Fedtsch (Apiaceae) and one of its main essential oil constituents, CA, focus on the mechanisms of action. METHODS: We used a molecular docking approach to examine the capability of CA for binding to IL-12P40 and TNF-α. The colorimetric assay was performed to assess the effect of B. persicum crude extract, essential oil, and CA, against Leishmania major promastigotes and intracellular amastigotes. The expression of IFN-γ, IL-12P40, TNF-α, and IL-10 genes was detected using quantitative real-time polymerase chain reaction qPCR. RESULTS: Docking analyses in the current study indicated CA binds to IL-12P40 and TNF-α. These products were safe, extremely antileishmanial, and significantly promoted Th1-related cytokines (IFN-γ, IL-12P40, TNF-α), while downregulating the Th2 phenotype (IL-10). CONCLUSION: Cumin essential oil and its major component, CA, possessed powerful antileishmanial activity. The primary mechanism of activity involves an immunomodulatory role toward Th1 cytokine response. Therefore, cumin essential oil and CA deserve further explorations as promising medications for treating leishmaniasis.
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Antiprotozoários , Apiaceae , Leishmania major , Óleos Voláteis , Óleos Voláteis/farmacologia , Subunidade p40 da Interleucina-12 , Interleucina-10 , Fator de Necrose Tumoral alfa , Simulação de Acoplamento Molecular , Apiaceae/química , Misturas Complexas , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêuticoRESUMO
The previous study indicated that cuminaldehyde (CUM) could be used as an antibacterial agent in sauced beef to reduce the propagation of Staphylococcus aureus (S. aureus). This research took sauced beef treated with 0.4 µL/mL CUM as the research object. Transcriptomic and proteomic methods were used to comprehensively analyze the changes in genes and proteins of S. aureus under CUM stress. A total of 258 differentially expressed genes (DEGs, 178 up-regulated and 80 down-regulated) and 384 differentially expressed proteins (DEPs, 61 up-regulated and 323 down-regulated) were found. It was observed that CUM destroyed the cell wall and cell membrane by inhibiting the synthesis of peptidoglycan and fatty acid. Low energy consumption strategies were formed by reducing glycolysis and ribosome de novo synthesis. The levels of genes and proteins associated with the glycine, serine, threonine, methionine, cysteine, and branched-chain amino acids were dramatically changed, which impaired protein synthesis and reduced bacterial viability. In addition, the up-regulated DEGs and DEFs involved in DNA replication, recombination and single-stranded DNA-binding contributed to DNA repair. Moreover, ATP-binding cassettes (ABC) transporters were also perturbed, such as the uptake of betaine and iron were inhibited. Thus, this study revealed the response mechanism of S. aureus under the stress of CUM, and provided a theoretical basis for the application of CUM in meat products.
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Infecções Estafilocócicas , Staphylococcus aureus , Trifosfato de Adenosina/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Benzaldeídos , Betaína/metabolismo , Bovinos , Cimenos , Cisteína , DNA de Cadeia Simples/metabolismo , Ácidos Graxos/metabolismo , Regulação Bacteriana da Expressão Gênica , Glicina/genética , Glicina/metabolismo , Ferro/metabolismo , Metionina/genética , Metionina/metabolismo , Peptidoglicano/genética , Proteômica , Serina/genética , Serina/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Treonina/genética , Treonina/metabolismo , TranscriptomaRESUMO
The interaction between cuminaldehyde and starch mainly governed the effect of further handling on food applications of cuminaldehyde. However, little information is available about the interactions of these components. We utilized relaxation and heteronuclear correlation (HETCOR) solid-state NMR spectroscopy to investigate the interaction between cuminaldehyde and porous starch at molecular level. We found that the interactions occurred mainly through hydrogen bonds. Cuminaldehyde molecules were restricted by starch, which resulted in the limitation of their movements and the longer 1H T1 relaxation time. Furthermore, the well resolved correlated peaks in 2D 1H-13C HETCOR spectrum confirmed the formation of hydrogen bonds. The oxygen atoms at hydroxyl-2,3 of starch were the binding sites, which combined with hydrogens of cuminaldehyde. This present work not only afford a new approach to obtain a molecular understanding of interactions, but also expanded the application of solid-state NMR to investigation of the interaction on functional components.
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Benzaldeídos/química , Cimenos/química , Ressonância Magnética Nuclear Biomolecular , Amido/química , Estrutura MolecularRESUMO
AIMS: Synthesis of novel drug delivery system for targeted delivery of cuminaldehyde to breast cancer cells and the subsequent analyses of anti-neoplastic potential of the drug. MAIN METHODS: 3-carboxy-phenyl boronic acid (PBA) conjugated and polyacrylic acid (PAA) gated mesoporous silica nanoparticles (MSNs) were synthesized for the targeted delivery of cuminaldehyde (CUM) to breast cancer cells. Enhancement of anti-neoplastic effects of cuminaldehyde (4-isopropylbenzaldehyde) by the nanoconjugates was assessed. KEY FINDINGS: The anti-cancer effects of non-targeted and targeted drug-nanoconjugates were examined in vitro and in vivo. The targeted drug-nanoconjugates caused cell cycle arrest and induced the intrinsic pathway of apoptosis in MCF-7 cells through mitochondrial damage. In vivo intravenous injection of the targeted drug-nanoconjugates led to effective reduction in growth of 4 T1 induced mammary pad tumor in female BALB/c mice via augmented accumulation of cuminaldehyde. The drug-nanoconjugates did not exhibit any systemic toxicity. SIGNIFICANCE: Therefore, MSN-PBA-CUM-PAA represents a potent therapeutic model for breast cancer treatment.
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Antineoplásicos , Neoplasias da Mama , Nanopartículas , Animais , Antineoplásicos/uso terapêutico , Benzaldeídos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Cimenos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Camundongos , Nanoconjugados/uso terapêutico , Porosidade , Dióxido de Silício/uso terapêuticoRESUMO
BACKGROUND: Animal-fats are rich in long-chain saturated fatty-acids, well known to induct diabetic distress among ingested insulin-insensitive individuals. In the current-study, bovine-fat was fed to selective mice breeds highly sensitized to heavy dietary lipid load. METHODS: The later high fat diet (HFD) group indeed undergone diabetic-onset within weeks with a drastically altered feed-behavior pattern. It consumed more food, gained body mass, elevated homeostatic model assessment value and extensively glycosylated Hb transporters. RESULTS: However, the hypothetical test drug (Cuminaldehyde or CA) with known therapeutic-potential worked-well to balance food efficiency-ratio and Hb- counts closer to control. The fat-soluble phytochemical mono-terpenoid (CA) promoted constitutive mono-hexose (glucose) consuming catabolic-cycles via mono-glycoprotein (insulin) signal-transduction. It resolved diabetogenic-upsurge of gluconeogenic-enzymes, reduced non-sugar (amino/fatty acids) utilization by restricting transamination/dephosphorylation and restored liver-glycogen reserves near to normal-group effectively at 10 mg/kg b.w dose. CONCLUSIONS: Hence, the nutraceutical-potential (anti-diabetes/transaminitis ability) of administered exogenous redox-active agent CA can be entertained for evoking therapeutic-heath in diabetic human-community.
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Diabetes Mellitus Experimental , Hiperglicemia , Resistência à Insulina , Humanos , Camundongos , Animais , Bovinos , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/farmacologia , Gorduras na Dieta/farmacologia , Resistência à Insulina/fisiologia , Fígado , Camundongos Endogâmicos C57BLRESUMO
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an essential oil obtained from the fruit of Cuminum cyminum L. (cumin oil), when used as a sensory additive in feed and water for drinking for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the use of cumin oil up to the maximum proposed use levels in feed of 15 mg/kg complete feed is considered as safe for all animal species. The FEEDAP Panel considered the use in water for drinking as safe provided that the total daily intake of the additive does not exceed the daily amount that is considered safe when consumed via feed. No concerns for consumers were identified following the use of cumin oil up to the maximum proposed use level in feed. The additive under assessment should be considered as irritant to skin and eyes, and as a dermal and respiratory sensitiser. When handling the essential oil, exposure of unprotected users to estragole (and dillapiole) cannot be excluded. Therefore, to reduce the risk, the exposure of the users should be minimised. The use of cumin oil at the proposed use level in feed is not expected to pose a risk to the environment. Since C. cyminum and its preparations are recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy is considered necessary.
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Cuminaldehyde (CA) is one of the major compounds of the essential oil of Cuminum cyminum. The aim of this study was to evaluate the effects of CA on aging, specifically on spatial learning and memory. To achieve our objective, an in vitro study on SH-SY5Y cells was performed to analyze the neuroprotective effect of CA against dexamethasone using the MTT assay. An in vivo study was performed for evaluation of the spatial learning and memory using Morris water maze (MWM). RT-PCR was performed to quantify the expression of specific genes (Bdnf, Icam and ApoE) in the mice brain. The results obtained showed a neuroprotective effect of CA against dexamethasone-induced neuronal toxicity. The escape latency of CA-treated aged mice was significantly decreased as compared to the water-treated aged mice after 4 days of training in MWM. Moreover, CA treatment up-regulated the gene expression of Bdnf, Icam and ApoE, while it down-regulated the gene expression of IL-6. These findings suggest that CA has a neuroprotective effect, as well as a spatial learning and memory enhancement potential through the modulation of genes coding for neurotrophic factors and/or those implicated in the imbalance of neural circuitry and impairment of synaptic plasticity. Cuminaldehyde (CA) is one of the major compound of the essential oil of Cuminum cyminum. The aim of this study was to evaluate the effects of CA on aging, specifically on spatial learning and memory. To achieve our objective, an in vitro study on SH-SY5Y cells was performed to analyze the neuroprotective effect of CA against dexamethasone using the MTT assay. An in vivo study was performed for evaluation of the spatial learning and memory using Morris water maze (MWM). RT-PCR was performed to quantify the expression of specific genes (Bdnf, Icam and ApoE) in the mice brain. The results obtained showed a neuroprotective effect of CA against dexamethasone-induced neuronal toxicity. The escape latency of CA-treated aged mice was significantly decreased as compared to the water-treated aged mice after 4 days of training in MWM. Moreover, CA treatment up-regulated the gene expression of Bdnf, Icam and ApoE, while it down-regulated the gene expression of IL-6. These findings suggest that CA has a neuroprotective effect, as well as a spatial learning and memory enhancement potential through the modulation of genes coding for neurotrophic factors and/or those implicated in the imbalance of neural circuitry and impairment of synaptic plasticity.
Assuntos
Envelhecimento/metabolismo , Benzaldeídos/administração & dosagem , Cimenos/administração & dosagem , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Memória Espacial/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Dieta , Dopamina/metabolismo , Epinefrina/metabolismo , Humanos , Interleucina-6/metabolismo , Camundongos , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
This work aimed to develop a novel nanoencapsulation system for food colloidal formulations using gelled lipid nanoparticles (GLNs) to improve the functionality, stability, and bioactivity of cuminaldehyde as a highly volatile and poor hydrophilic food additive. Cuminaldehyde-loaded GLNs with diameters of 117-138 nm were fabricated through a hot emulsification process with monoglyceride (10 and 15 g/100 g lipid phase) as a lipid gelator at two concentrations of cuminaldehyde (500 and 1000 mg/L). All samples remained stable towards macroscopic phase separation and creaming during 28 days of storage at 4 °C, which could be related to the rigid structure of dispersed particles in the gelled state and retarding droplet movement. Moreover, all samples were stable to creaming after subjecting to the environmental changes including temperature (30, 60, and 90 °C for 30 min), ionic strength (100, 200, and 300 mM NaCl), and pH (3, 5, and 7). Measurement of apparent viscosity showed non-Newtonian shear thinning nature in all samples, which was more pronounced at higher concentrations of the gelator. Interestingly, higher cytotoxic effects of cuminaldehyde against human lung and colorectal cancer cells were observed after encapsulation within GLNs. However, weak toxicity was also found against normal peripheral blood mononuclearcells.On the other hand, the antioxidant activity and lipid oxidation stability were improved by increasing cuminaldehyde concentration, while it was reduced at higher monoglyceride concentration. All samples exhibited stronger antibacterial activity against Bacillus cereus than Eschershia coli. These findings suggest the significant potential benefits of GLNs as novel nanocarriers to enrich various food and beverage formulations with essential oils, flavors, and aromas.
Assuntos
Antioxidantes , Nanopartículas , Antibacterianos/farmacologia , Benzaldeídos , Cimenos , Humanos , Lipossomos , Tamanho da PartículaRESUMO
Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.