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1.
Nat Commun ; 15(1): 4943, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858372

ABSTRACT

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2-•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2-• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.


Subject(s)
Benzoquinones , Photochemotherapy , Photosensitizing Agents , Staphylococcus aureus , Benzoquinones/chemistry , Benzoquinones/pharmacology , Benzoquinones/metabolism , Photosensitizing Agents/pharmacology , Animals , Mice , Female , Photochemotherapy/methods , Electron Transport/drug effects , Staphylococcus aureus/drug effects , Cymenes/pharmacology , Cymenes/chemistry , Anti-Bacterial Agents/pharmacology , Singlet Oxygen/metabolism , Superoxides/metabolism , Staphylococcal Infections/drug therapy , Humans , Light , Mice, Inbred BALB C
2.
Molecules ; 29(10)2024 May 12.
Article in English | MEDLINE | ID: mdl-38792138

ABSTRACT

Cancer is ranked among lethal diseases globally, and the increasing number of cancer cases and deaths results from limited access to effective therapeutics. The use of plant-based medicine has been gaining interest from several researchers. Carvacrol and its isomeric compound, thymol, are plant-based extracts that possess several biological activities, such as antimalarial, anticancer, antifungal, and antibacterial. However, their efficacy is compromised by their poor bioavailability. Thus, medicinal scientists have explored the synthesis of hybrid compounds containing their pharmacophores to enhance their therapeutic efficacy and improve their bioavailability. Hence, this review is a comprehensive report on hybrid compounds containing carvacrol and its isomer, thymol, with potent anticancer and antibacterial agents reported between 2020 and 2024. Furthermore, their structural activity relationship (SAR) and recommended future strategies to further enhance their therapeutic effects will be discussed.


Subject(s)
Anti-Bacterial Agents , Antineoplastic Agents , Cymenes , Thymol , Thymol/chemistry , Thymol/pharmacology , Cymenes/chemistry , Cymenes/pharmacology , Cymenes/therapeutic use , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Neoplasms/drug therapy , Animals
3.
Cell Biochem Funct ; 42(4): e4062, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38807490

ABSTRACT

Since most solid tumors have a low pH value, a pH-responsive drug delivery system may offer a broad method for tumor-targeting treatment. The present study is used to analyze the anticancer activity of carvacrol-zinc oxide quantum dots (CVC-ZnO QDs) against breast cancer cells (MDA-MB-231). CVC-ZnO QDs demonstrate pH responsive and are specifically released within the acidic pH tumor microenvironment. This property enables targeted drug delivery exclusively to cancer cells while minimizing the impact on normal cells. To the synthesized ZnO QDs, the CVC was loaded and then examined by X-ray diffraction, ultraviolet-visible, Fourier transform infrared spectrophotometer, scanning electron microscopy-energy dispersive X-ray, and transmission electron microscopy. For up to 20 h, CVC release was examined in different pH-buffered solutions. The results showed that carvacrol release was stable in an acidic pH solution. Further, cytotoxicity assay, antioxidant, and lipid peroxidation activity, reactive oxygen species, mitochondrial membrane potential, nuclear damage, and the ability of CVC-ZnO QDs to cause apoptosis were all examined. Apoptosis markers such as Bcl2, Bax, caspase-3, and caspase-9, were also studied. In conclusion, the CVC-ZnO QDs destabilized the MDA-MB-231cells under its acidic tumor microenvironment and regulated apoptosis.


Subject(s)
Antineoplastic Agents , Apoptosis , Breast Neoplasms , Cymenes , Quantum Dots , Zinc Oxide , Humans , Quantum Dots/chemistry , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Zinc Oxide/chemical synthesis , Cymenes/pharmacology , Cymenes/chemistry , Hydrogen-Ion Concentration , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Female , Apoptosis/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , Membrane Potential, Mitochondrial/drug effects
4.
Asian Pac J Cancer Prev ; 25(5): 1663-1671, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38809638

ABSTRACT

BACKGROUND: Cancer is a challenge for either the patient or the healthcare manager. Treatment protocols based on chemotherapy or radiotherapy, or both are interfering with the patient's life making him suffer rather than being alleviated. This burden pushed the scientists to search for new regimens that may help ameliorate patient as well as doctor inconvenience. Benefits of plant extracts as medical substitutes in cancer management have been proved. New nano formulated drug delivery systems may help overcoming remedy regimens barriers and obstacles. The present research topic aims to evaluate the anticancer power of two plant extracts in nano emulsion formulation on human melanoma cell line. METHODS: Carvacrol and rosemary essential oils were obtained, and nano emulsions were formulated. NE were characterized using TEM for charge and size distribution. The A375 human melanoma cell line was cultured and propagated then IC50 of prepared NE was added. Assessment of cell cytotoxicity, effect on angiogenesis and apoptosis were tested. RESULTS: After synthesis and characterization, both carvacrol nano emulsion (CNE) and rosemary nano emulsion (RNE) were capable of inhibiting melanoma cell line viability, angiogenesis and they enhanced the expression of caspase-3 proapoptotic marker. CONCLUSION: Rosemary and carvacrol extract nano emulsions could be a new revolutionary agent in human melanoma therapy and these formulations can be applied locally.


Subject(s)
Apoptosis , Cymenes , Emulsions , Melanoma , Oils, Volatile , Plant Extracts , Humans , Emulsions/chemistry , Melanoma/drug therapy , Melanoma/pathology , Plant Extracts/pharmacology , Apoptosis/drug effects , Cymenes/pharmacology , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Nanoparticles/chemistry , Cell Proliferation/drug effects , Tumor Cells, Cultured , Cell Survival/drug effects , Cell Line, Tumor , Drug Delivery Systems
5.
Int J Food Microbiol ; 418: 110713, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38718617

ABSTRACT

This research aimed to assess the potential of active food packaging as an innovative approach to enhance the quality of fresh food products. Specifically, our focus was on developing chitosan edible films combined with rosemary nanoemulsion (Ch-RNE) and carvacrol nano-emulsion (Ch-CNE) as effective antibacterial food packaging solutions. The efficacy of these films against artificially inoculated L. monocytogenes (NCTC 13372\ ATCC® 7644) as a Gram-positive bacterium, and S. enterica serovar Typhimurium (ATCC 14028) as a Gram-negative bacterium, in ground meat was investigated. The size of the prepared nano-emulsions was characterized using zeta sizer, FTIR and HRTEM. The MIC of both nano-emulsions against both pathogens was found to be 0.78 % and 1.56 %. Filmogenic mixtures were casted using these concentrations, which were then dried and evaluated for their physical and mechanical properties.


Subject(s)
Anti-Bacterial Agents , Chitosan , Cymenes , Edible Films , Emulsions , Food Packaging , Listeria monocytogenes , Monoterpenes , Salmonella typhimurium , Cymenes/pharmacology , Chitosan/pharmacology , Chitosan/chemistry , Listeria monocytogenes/drug effects , Listeria monocytogenes/growth & development , Salmonella typhimurium/drug effects , Salmonella typhimurium/growth & development , Emulsions/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Food Packaging/methods , Monoterpenes/pharmacology , Rosmarinus/chemistry , Microbial Sensitivity Tests , Food Microbiology , Meat Products/microbiology , Food Preservation/methods
6.
Biochim Biophys Acta Biomembr ; 1866(5): 184332, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740123

ABSTRACT

The mechanism of chemotherapeutic action of Ru-based drugs involves plasma membrane disruption and valuable insights into this process may be gained using cell membrane models. The interactions of a series of cytotoxic η6-p-cymene ruthenium(II) complexes, [Ru(η6-p-cymene)P(3,5-C(CH3)3-C6H3)3Cl2] (1), [Ru(η6-p-cymene)P(3,5-CH3-C6H3)3Cl2] (2), [Ru(η6-p-cymene)P(4-CH3O-3,5-CH3-C6H2)3Cl2] (3), and [Ru(η6-p-cymene)P(4-CH3O-C6H4)3Cl2] (4), were examined using Langmuir monolayers as simplified healthy and cancerous outer leaflet plasma membrane models. The cancerous membrane (CM1 and CM2) models contained either 40 % 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 30 % cholesterol (Chol), 20 % 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and 10 % 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine (DPPS). Meanwhile, the healthy membrane (HM1 and HM2) models were composed of 60 % DPPC or DOPC, 30 % Chol and 10 % DPPE. The complexes affected surface pressure isotherms and decreased compressional moduli of cancerous and healthy membrane models, interacting with the monolayers headgroup and tails according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). However, the effects did not correlate with the toxicity of the complexes to cancerous and healthy cells. Multidimensional projection technique showed that the complex (1) induced significant changes in the CM1 and HM1 monolayers, though it had the lowest cytotoxicity against cancer cells and is not toxic to healthy cells. Moreover, the most toxic complexes (2) and (4) were those that least affected CM2 and HM2 monolayers. The findings here support that the ruthenium complexes interact with lipids and cholesterol in cell membrane models, and their cytotoxic activities involve a multifaceted mode of action beyond membrane disruption.


Subject(s)
Cell Membrane , Cymenes , Ruthenium , Cymenes/chemistry , Cymenes/pharmacology , Cell Membrane/drug effects , Cell Membrane/chemistry , Ruthenium/chemistry , Ruthenium/pharmacology , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Monoterpenes/chemistry , Monoterpenes/pharmacology , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Phosphatidylcholines/chemistry
7.
Biomed Pharmacother ; 175: 116692, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701569

ABSTRACT

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.


Subject(s)
Benzaldehydes , Benzoquinones , Carbon Tetrachloride , Gallic Acid , Kidney , Lung , NF-kappa B , Oxidative Stress , Reactive Oxygen Species , Signal Transduction , Animals , Gallic Acid/pharmacology , Benzoquinones/pharmacology , Signal Transduction/drug effects , Male , NF-kappa B/metabolism , Reactive Oxygen Species/metabolism , Rats , Carbon Tetrachloride/toxicity , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Benzaldehydes/pharmacology , Lung/drug effects , Lung/pathology , Lung/metabolism , Oxidative Stress/drug effects , Molecular Docking Simulation , Cymenes/pharmacology , Protective Agents/pharmacology , Antioxidants/pharmacology , Lipid Peroxidation/drug effects , Rats, Wistar , Rats, Sprague-Dawley
8.
Food Res Int ; 187: 114458, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763690

ABSTRACT

This study examines the antimicrobial and antibiofilm effectiveness of baicalin and carvacrol against Salmonella enterica ser. Typhimurium on food contact surfaces and chicken meat. The minimum inhibitory concentrations (MIC) for baicalin and carvacrol were found to be 100 µg/mL and 200 µg/mL, respectively, which aligns with findings from previous studies. The compounds exhibited a concentration-dependent decrease in microbial populations and biofilm formation. When used together, they displayed a remarkable synergistic effect, greatly augmenting their antibacterial activity. The assessment of food quality demonstrated that these treatments have no negative impact on the sensory characteristics of chicken meat. The impact of the structure on biofilms was observed through the use of Field Emission Scanning Electron Microscopy (FE-SEM) and Confocal Laser Scanning Microscopy (CLSM), revealing disrupted biofilm architectures and decreased cell viability. Crucially, RT-PCR analysis revealed a marked downregulation of quorum sensing (luxS), virulence (hilA), and stress response (rpoS) genes, highlighting the multifaceted antimicrobial mechanism of action. This gene-specific suppression suggests a targeted disruption of bacterial communication and virulence pathways, offering insight into the comprehensive antibiofilm strategy. This provides further insight into the molecular mechanisms that contribute to their antibiofilm effects.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chickens , Cymenes , Flavonoids , Food Microbiology , Microbial Sensitivity Tests , Salmonella typhimurium , Biofilms/drug effects , Cymenes/pharmacology , Salmonella typhimurium/drug effects , Flavonoids/pharmacology , Anti-Bacterial Agents/pharmacology , Animals , Quorum Sensing/drug effects , Meat/microbiology , Monoterpenes/pharmacology , Microscopy, Electron, Scanning
9.
Exp Eye Res ; 244: 109938, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38789020

ABSTRACT

Neurodegenerative pathologies affecting the posterior segment of the eye, are characterized by being devastating and responsible for the majority of visual dysfunctions worldwide. These diseases are primarily degenerative, progressing chronically, and can inflict gradual harm to the optic nerve, retinal ganglion cells (RGC), photoreceptors, and other retinal cells. This retinal damage leads to a progressive loss of vision, marking these conditions as a significant health concern worldwide. The intravitreal administration of the phytochemical Carvacrol (CAR) is expected to demonstrate a neuroprotective and antiapoptotic effect on retinal cells, with a specific focus on RGC. This effect will be observed in a retinal degeneration model (RDM) in rabbits induced by cytotoxic and oxidative agents, namely glutamate (GLUT) and L-buthionine-S, R-sulfoximine (BSO). An in vivo study was conducted using New Zealand rabbits in which retinal damage was created to evaluate the effectiveness of CAR. The effectiveness of CAR on the functionality of retinal neuronal cells in RDM was evaluated using pupillary light reflection (PLR). Furthermore, the phytotherapeutic's influence on cell viability was determined through flow cytometry analysis. Finally, the neuroprotective and antiapoptotic capabilities of CAR were specifically scrutinized in RGC through histological studies, quantifying cell survival, and employing immunohistochemical assays to detect the apoptotic index (%) using the TUNEL technique. Our results demonstrated that CAR promoted the recovery of the pupillary contraction profile over time, maintaining the functionality of retinal cells as healthy controls. Additionally, it showed increased cell viability under oxidative and cytotoxic conditions given by GLUT-BSO agents. Finally, we found that CAR protects the survival of RGC and decreases the percentage of apoptotic cells when compared to RDM. CAR demonstrated to have positive effects on the functionality of photoreceptive nerve cells by restoring pupillary contraction. Likewise, it was shown to have neuroprotective and antiapoptotic effects when evaluated in a general and specific way on retinal nerve cells.


Subject(s)
Cell Survival , Cymenes , Disease Models, Animal , Retinal Degeneration , Retinal Ganglion Cells , Animals , Rabbits , Retinal Degeneration/prevention & control , Retinal Degeneration/pathology , Retinal Degeneration/metabolism , Cymenes/pharmacology , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/pathology , Cell Survival/drug effects , Apoptosis/drug effects , Neuroprotective Agents/pharmacology , Intravitreal Injections , Flow Cytometry , Reflex, Pupillary/drug effects , Reflex, Pupillary/physiology
10.
Sci Rep ; 14(1): 9218, 2024 04 22.
Article in English | MEDLINE | ID: mdl-38649444

ABSTRACT

For reducing Campylobacter (C.) in the food production chain and thus the risk to the consumer, the combined application of different measures as a multiple-hurdle approach is currently under discussion. This is the first study to investigate possible synergistic activities in vivo, aiming at reducing intestinal C. jejuni counts by administering (i) bacteriophages (phages) in combination with a competitive exclusion (CE) product and (ii) carvacrol combined with organic acids. The combined application of the two selected phages (Fletchervirus phage NCTC 12673 and Firehammervirus phage vB_CcM-LmqsCPL1/1) and the CE product significantly reduced C. jejuni loads by 1.0 log10 in cecal and colonic contents as well as in cloacal swabs at the end of the trial (33 and 34 days post hatch). The proportion of bacterial isolates showing reduced phage susceptibility ranged from 10.9% (isolates from cecal content) to 47.8% (isolates from cloacal swabs 32 days post hatch) for the Fletchervirus phage, while all tested isolates remained susceptible to the Firehammervirus phage. The use of carvacrol combined with an organic acid blend (sorbic acid, benzoic acid, propionic acid, and acetic acid) significantly reduced Campylobacter counts by 1.0 log10 in cloacal swabs on day 30 only.


Subject(s)
Bacteriophages , Chickens , Cymenes , Cymenes/pharmacology , Animals , Bacteriophages/physiology , Chickens/microbiology , Campylobacter Infections/prevention & control , Campylobacter Infections/microbiology , Poultry Diseases/microbiology , Poultry Diseases/prevention & control , Poultry Diseases/virology , Campylobacter jejuni/virology , Campylobacter jejuni/drug effects , Campylobacter/drug effects , Campylobacter/virology
11.
Brain Res ; 1836: 148954, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38649135

ABSTRACT

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder whose cause is unclear. Neuroinflammation is recognized as one of the major pathogenic mechanisms involved in the development and progression of PD. NLRP3 inflammasome is the most widely studied inflammatory mediator in various diseases including PD. Several phytoconstituents have shown neuroprotective role in PD. Carvacrol is a phenolic monoterpene commonly found in the essential oils derived from plants belonging to Lamiaceae family. It is well known for its anti-inflammatory and antioxidant properties and has been widely explored in several diseases. In this study, we explored the role of Carvacrol in suppressing neuroinflammation by regulating NLRP3 inflammasome through Nrf2/HO-1 axis and subsequently, inflammatory cytokines like IL-1ß, IL-18 in Rotenone induced PD mice model. Three doses (25 mg/kg, 50 mg/kg, 100 mg/kg p.o.) of Carvacrol were administered to, respectively, three groups (LD, MD, HD), one hour after administration of Rotenone (1.5 mg/kg, i.p.), every day, for 21 days. Treatment with Carvacrol ameliorated the motor impairment caused by Rotenone. It alleviated neurotoxicity and reduced inflammatory cytokines. Further, Carvacrol also alleviated oxidative stress and increased antioxidant enzymes. From these results, we show that Carvacrol exerts neuroprotective effects in PD via anti-inflammatory and antioxidant mechanisms and could be a potential therapeutic option in PD.


Subject(s)
Cymenes , Disease Models, Animal , NF-E2-Related Factor 2 , NLR Family, Pyrin Domain-Containing 3 Protein , Neuroprotective Agents , Rotenone , Animals , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Cymenes/pharmacology , Mice , Neuroprotective Agents/pharmacology , Male , Inflammasomes/metabolism , Inflammasomes/drug effects , Heme Oxygenase (Decyclizing)/metabolism , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Oxidative Stress/drug effects , Antioxidants/pharmacology , Membrane Proteins , Heme Oxygenase-1
12.
J Appl Microbiol ; 135(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38587823

ABSTRACT

AIM: In this study, it was aimed to examine the antibacterial activity of the essential oil components (EOCs), carvacrol (CAR), cinnamaldehyde (CIN), thymol (TH), alpha pinene (α-PN), eucalyptol (EU), limonene (LIM), and the antibiotics, linezolid (LZD), vancomycin (VAN), gentamicin (GEN), ciprofloxacin (CIP), clindamycin (CLN), and penicillin (PEN) against 50 multidrug resistant Corynebacterium striatum strains, and the synergistic interactions of CAR and CIN with the antibiotics against 10 randomly selected Coryne. striatum strains to explore synergistic interactions to determine if their combined use could enhance antibiotic activity and potentially reduce resistance. METHODS AND RESULTS: The activity of the EOCs and the antibiotics against Coryne. striatum strains isolated from clinical specimens, was examined by broth microdilution method. The synergistic interactions of the EOCs with the antibiotics against 10 randomly selected Coryne. striatum strains were determined by checkerboard method. EOCs, CIN, and CAR and antibiotics, LZD, VAN, GEN, CIP, and CLN were detected to have antibacterial activity against Coryne. striatum strains alone and either synergistic interactions were observed in combinations of the antibiotics with EOCs. CONCLUSIONS: All Coryne. striatum strains were determined to be susceptible to VAN and LZD and resistant to GEN, PEN, CIP, and CLN. Synergistic interactions were observed in all combinations of antibiotics tested with CAR and CIN.


Subject(s)
Acrolein , Acrolein/analogs & derivatives , Anti-Bacterial Agents , Corynebacterium , Drug Resistance, Multiple, Bacterial , Drug Synergism , Microbial Sensitivity Tests , Monoterpenes , Oils, Volatile , Anti-Bacterial Agents/pharmacology , Corynebacterium/drug effects , Oils, Volatile/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Acrolein/pharmacology , Monoterpenes/pharmacology , Cymenes/pharmacology , Ciprofloxacin/pharmacology , Gentamicins/pharmacology , Vancomycin/pharmacology , Linezolid/pharmacology , Limonene/pharmacology , Eucalyptol/pharmacology , Thymol/pharmacology , Clindamycin/pharmacology , Humans , Penicillins/pharmacology , Terpenes/pharmacology , Cyclohexenes/pharmacology , Corynebacterium Infections/microbiology
13.
Exp Appl Acarol ; 92(3): 555-565, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38468022

ABSTRACT

The main way to avoid contact with ticks and consequently tick-borne disease is the use of synthetic repellents. The search of new repellent compounds to increase the possibilities of use in strategies controls are necessary. The present study evaluated the repellent activity of two natural terpenes carvacrol and thymol in each one two different formulation (encapsulated and nonencapsulated with yeast cell wall) against the ticks Amblyomma sculptum and Rhipicephalus sanguineus sensu lato nymphs. Nymphs of A. sculptum and R. sanguineus s.l. of a single generation were used. The vertical filter paper repellency assay were performed with different concentration of both terpenes encapsulated and nonencapsulated in yeast cell wall. The repellent concentration 50% (RC50) were calculated to each compound formulation. Both carvacrol and thymol (encapsulated and nonencapsulated), had a repellent activity against A. sculptum and R. sanguineus s.l nymphs. Amblyomma sculptum was more sensitive to nonencapsulated carvacrol (RC50 values: 0.0032 to 0.0082 mg/cm2 after 1 and 15 min) (P < 0.05), while R. sanguineus s.l. was more sensitive to encapsulated carvacrol (RC50 values: 0.00008 to 0.0035 mg/cm2 after 1 and 15 min) (P < 0.05). Among tick species, R. sanguineus s.l. was more sensitive for most compounds than A. sculptum (P < 0.05). Although with distinct repellent activities, carvacrol and thymol encapsulated can be a promising alternative to synthetic repellents against A. sculptum and R. sanguineus s.l.


Subject(s)
Amblyomma , Cymenes , Nymph , Rhipicephalus sanguineus , Thymol , Cymenes/pharmacology , Animals , Thymol/pharmacology , Nymph/drug effects , Nymph/growth & development , Rhipicephalus sanguineus/drug effects , Cell Wall/drug effects , Acaricides/pharmacology , Monoterpenes/pharmacology , Insect Repellents/pharmacology , Saccharomyces cerevisiae/drug effects
14.
Int J Biol Macromol ; 266(Pt 1): 130937, 2024 May.
Article in English | MEDLINE | ID: mdl-38521301

ABSTRACT

Herein, carvacrol (CRV) and modified cellulose nanocrystal-zinc oxide (CNC-ZnO) were incorporated into a poly (lactic acid) (PLA) matrix to prepare a PLA-based composite film using a simple solution casting method to achieve antimicrobial effects for application in antimicrobial food packaging. Compared with films obtained from neat PLA, the PLA@CRV20%@CNC-ZnO3% composite film shows better performance in terms of mechanical properties, ultraviolet (UV) blocking, and antimicrobial effects. The PLA composites containing CRV and 3 wt% CNC-ZnO blends exhibit improved tensile strength (21.8 MPa) and elongation at break (403.1 %) as well as excellent UV resistance. In particular, CRV and the CNC-ZnO hybrid endow the obtained PLA composite films with a synergistic antibacterial effect, resulting in good antibacterial properties for microbes, such as Escherichia coli, Staphylococcus aureus and Aspergillus niger. The diameters of the inhibition zone of the PLA@CRV20%@CNC-ZnO3% composite films against E. coli, S. aureus, and A. niger were 4.9, 5.0, and 3.4 cm, respectively. Appling the PLA@CRV20%@CNC-ZnO3% composite film as an antibacterial food packaging material, the storage period for strawberries was considerably extended. This study provides a theoretical basis for developing new organic/inorganic composite antimicrobial film materials from PLA.


Subject(s)
Anti-Bacterial Agents , Cellulose , Cymenes , Food Packaging , Nanoparticles , Polyesters , Zinc Oxide , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Polyesters/chemistry , Cymenes/chemistry , Cymenes/pharmacology , Cellulose/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanoparticles/chemistry , Food Packaging/methods , Staphylococcus aureus/drug effects , Nanocomposites/chemistry , Escherichia coli/drug effects , Tensile Strength , Microbial Sensitivity Tests , Aspergillus niger/drug effects
15.
Int J Biol Macromol ; 266(Pt 1): 131250, 2024 May.
Article in English | MEDLINE | ID: mdl-38556241

ABSTRACT

In recent years, the application of biopolymer-based nanofibers prepared via microfluidic blow spinning (MBS) for food packaging has continuously increased due to their advantages of biocompatibility, biodegradability, and safety. However, the poor spinnability, undesirable water barrier capacity, and loss of antibacterial and antioxidant properties of biopolymer-based nanofibers strictly restrict their real-world applications. In this work, carvacrol (CV) incorporated konjac glucomannan (KGM)/polylactic acid (PLA) nanofibrous films (KP-CV) were produced by MBS. The FTIR spectra and XRD analysis revealed the hydrogen bonding interactions among CV, PLA, and KGM, thus significantly improving the TS of KP-CV nanofibrous films from 0.23 to 1.27 MPa with increased content of CV from 0 % to 5 %. Besides, KP-CV nanofibrous films showed improved thermal stability, excellent hydrophobicity (WCA: 128.19°, WVP: 1.02 g mm/m2 h kPa), and sustained release of CV combined with good antioxidant activities (DPPH radical scavenging activity: 77.51 ± 1.57 %), and antibacterial properties against S. aureus (inhibition zone: 26.33 mm) and E. coli (inhibition zone: 22.67 mm). Therefore, as prepared KP-CV nanofibrous films can be potentially applied as packaging materials for the extended shelf life of cherry tomatoes.


Subject(s)
Antioxidants , Cymenes , Food Packaging , Mannans , Nanofibers , Polyesters , Food Packaging/methods , Mannans/chemistry , Polyesters/chemistry , Cymenes/chemistry , Cymenes/pharmacology , Nanofibers/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrophobic and Hydrophilic Interactions , Escherichia coli/drug effects , Staphylococcus aureus/drug effects
16.
Microb Pathog ; 190: 106624, 2024 May.
Article in English | MEDLINE | ID: mdl-38492828

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Benzaldehydes , Biofilms , Ciprofloxacin , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Reactive Oxygen Species , Biofilms/drug effects , Ciprofloxacin/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Anti-Bacterial Agents/pharmacology , Benzaldehydes/pharmacology , Reactive Oxygen Species/metabolism , Virulence Factors , Cymenes/pharmacology , Drug Synergism , Cell Membrane Permeability/drug effects , Humans
17.
Future Med Chem ; 16(7): 679-688, 2024 04.
Article in English | MEDLINE | ID: mdl-38390753

ABSTRACT

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.


Subject(s)
Mycobacterium tuberculosis , Molecular Docking Simulation , Cymenes/pharmacology , Anti-Bacterial Agents/pharmacology
18.
Parasitol Res ; 123(1): 48, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38095726

ABSTRACT

The tick Rhipicephalus sanguineus is one of the main ectoparasites that affects dogs, causing direct and indirect damage to parasitized animals. Currently, infestation control is mainly carried out by using synthetic acaricidal drugs. However, a decrease in efficacy and an increase in resistance to the main therapeutic protocols against tick infestations have been increasingly reported and confirmed, a factor that has driven research into the potential acaricide activity of natural compounds, including in association with synthetic molecules. The aim of this work was to evaluate whether the combinations of fipronil (FIP) and eugenol (EUG), FIP and carvacrol (CAR), and EUG and CAR would have synergistic effects against immature and unfed adult stages of R. sanguineus through in vitro bioassays. Bioassays were carried out using the larval packet test (FAO 2004) adapted for nymphs and adults. The synergistic activity was explored by combining each solution, based on the estimated LC50, in a 1:1 ratio (FIP: EUG, FIP: CAR and EUG: CAR). CompuSyn software was used to evaluate the various pairwise combinations of FIP, EUG and CAR, checking if there was synergism or antagonism between them. FIP and EUG and FIP and CAR showed combination index (CIn) values above 1.45, indicating antagonism. The synergistic activity between EUG and CAR was verified against all unfed phases of R. sanguineus, since the CIn was below 0.70, a value that indicates synergism. The combination of fipronil with either eugenol or carvacrol presented antagonistic effects against R. sanguineus larvae. On the other hand, carvacrol and eugenol had excellent pharmacological synergism against all tick stages with mortality values in the range of 80 to 100%, including the adult stage, which is less susceptible than immature stages.


Subject(s)
Acaricides , Rhipicephalus sanguineus , Tick Infestations , Animals , Dogs , Acaricides/pharmacology , Acaricides/therapeutic use , Cymenes/pharmacology , Cymenes/therapeutic use , Eugenol/pharmacology , Eugenol/therapeutic use , Larva , Rhipicephalus sanguineus/drug effects , Tick Infestations/drug therapy , Tick Infestations/veterinary , Drug Synergism , Drug Therapy, Combination
19.
Inorg Chem ; 62(30): 11761-11774, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37459067

ABSTRACT

Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea ligands, bearing the general formula [(η6-p-cymene)RuCl2(L)] (1-6) and [(η6-p-cymene)RuCl(L)(PPh3)]+ (7--12), have been synthesized and characterized. In contrast to the spectroscopic data which revealed monodentate coordination of the ligands to the Ru(II) ion via a "S" atom, single crystal X-ray structures revealed an unusual bidentate N, S coordination with the metal center forming a four-membered ring. Interaction studies by absorption, emission, and viscosity measurements revealed intercalation of the Ru(II) complexes with calf thymus (CT) DNA. The complexes showed good interactions with bovine serum albumin (BSA) as well. Further, their cytotoxicity was explored exclusively against breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231, wherein all of the complexes were found to display more pronounced activity than their ligand counterparts. Complexes 7-12 bearing triphenylphosphine displayed significant cytotoxicity, among which complex 12 showed IC50 values of 0.6 ± 0.9, 0.1 ± 0.8, and 0.1 ± 0.2 µM against MCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most active complexes were tested for their mode of cell death through staining assays, which confirmed apoptosis. The upregulation of apoptotic inducing and downregulation of apoptotic suppressing proteins as inferred from the western blot analysis also corroborated the apoptotic mode of cell death. The active complexes effectively generated reactive oxygen species (ROS) in MDA-MB-231 cells as analyzed from the 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Finally, in vivo studies of the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealed that treatment with these complexes at high doses of up to 8 mg/kg did not induce any visible damage to the tested organs.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Neoplasms , Ruthenium , Animals , Mice , Ligands , Coordination Complexes/chemistry , Cymenes/pharmacology , Cymenes/chemistry , Apoptosis , Antineoplastic Agents/chemistry , Ruthenium/pharmacology , Ruthenium/chemistry , Cell Line, Tumor
20.
J Vis Exp ; (194)2023 04 07.
Article in English | MEDLINE | ID: mdl-37092818

ABSTRACT

Lab coats are widely used in biohazard laboratories and healthcare facilities as protective garments to prevent direct exposure to pathogens, spills, and burns. These cotton-based protective coats provide ideal conditions for microbial growth and attachment sites due to their porous nature, moisture-holding capacity, and retention of warmth from the user's body. Several studies have demonstrated the survival of pathogenic bacteria on hospital garments and lab coats, acting as vectors of microbial transmission. A common approach to fix these problems is the application of antimicrobial agents in textile finishing, but concerns have been raised due to the toxicity and environmental effects of many synthetic chemicals. The ongoing pandemic has also opened a window for the investigation of effective antimicrobials and eco-friendly and toxic-free formulations. This study uses two natural bioactive compounds, carvacrol and thymol, encapsulated in chitosan nanoparticles, which guarantee effective protection against four human pathogens with up to a 4-log reduction (99.99%). These pathogens are frequently detected in lab coats used in biohazard laboratories. The treated fabrics also resisted up to 10 wash cycles with 90% microbial reduction, which is sufficient for the intended use. We made modifications to the existing standard fabric tests to better represent the typical scenarios of lab coat usage. These refinements allow for a more accurate evaluation of the effectiveness of antimicrobial lab coats and for the simulation of the fate of any accidental microbial spills that must be neutralized within a short time. Further studies are recommended to investigate the accumulation of pathogens over time on antimicrobial lab coats compared to regular protective coats.


Subject(s)
Anti-Infective Agents , Cymenes , Disinfectants , Nanocapsules , Oils, Volatile , Plant Preparations , Protective Clothing , Thymol , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Nanocapsules/chemistry , Plant Preparations/chemistry , Plant Preparations/pharmacology , Protective Clothing/microbiology , Laboratories , Textiles/microbiology , Disinfectants/chemistry , Disinfectants/pharmacology , Thymol/chemistry , Thymol/pharmacology , Cymenes/chemistry , Cymenes/pharmacology , Disk Diffusion Antimicrobial Tests
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