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1.
Turkiye Parazitol Derg ; 48(2): 72-76, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38958374

RESUMEN

Objective: Trichomonas vaginalis is a sexually transmitted protozoan parasite that usually causes infections in women. Metronidazole is used as the first choice in the treatment of this parasitic disease, but there is a need for new drugs since 1980's with increasing numbers of reported resistance. In this study, it was aimed to determine the antitrichomonal activity of the major components of Cinnamomum zeylanicum (cinnamon) and Thymus vulgaris (thyme) essential oils, cinnamaldehyde, carvacrol and thymol against metronidazole resistant and susceptible T. vaginalis strains, and to determine their interaction with metronidazole by checkerboard method. Methods: Cinnamaldehyde, carvacrol, thymol and metronidazole were obtained commercially. Two clinical isolates and one metronidazole resistant T. vaginalis reference strain were used in the study. MIC50 and MLC values of essential oil components and metronidazole were determined by broth microdilution method. The combinations of essential oil components with metronidazole were determined by the checkerboard method. Results: According to in vitro activity tests, cinnamaldehyde was determined to be most effective essential oil component. Clinical isolates were susceptible to metronidazole. In combination study, metronidazole showed synergy with cinnamaldehyde and carvacrol, and partial synergy with thymol. Conclusion: It was determined that cinnamaldehyde, carvacrol and thymol, which are known to have high antimicrobial activity, also have strong activity against T. vaginalis isolates and show a synergistic interaction with metronidazole. The use of metronidazole at lower doses in the synergistic interaction may contribute to the literature in terms of reducing drug side effects, creating a versatile antimicrobial target, and reducing the rate of resistance development.


Asunto(s)
Acroleína , Cimenos , Sinergismo Farmacológico , Metronidazol , Monoterpenos , Aceites Volátiles , Timol , Thymus (Planta) , Trichomonas vaginalis , Acroleína/análogos & derivados , Acroleína/farmacología , Timol/farmacología , Cimenos/farmacología , Metronidazol/farmacología , Humanos , Aceites Volátiles/farmacología , Thymus (Planta)/química , Trichomonas vaginalis/efectos de los fármacos , Monoterpenos/farmacología , Femenino , Cinnamomum zeylanicum/química , Antiprotozoarios/farmacología , Pruebas de Sensibilidad Microbiana , Resistencia a Medicamentos
2.
ACS Appl Mater Interfaces ; 16(28): 36017-36029, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38975983

RESUMEN

Oral infectious diseases have a significant impact on the health of oral and maxillofacial regions, as well as the overall well-being of individuals. Carvacrol and thymol, two isomers known for their effective antibacterial and anti-inflammatory properties, have gained considerable attention in the treatment of oral infectious diseases. However, their application as topical drugs for oral use is limited due to their poor physical and chemical stability. UiO-66, a metal-organic framework based on zirconium ion (Zr4+), exhibits high drug loading capability. Carvacrol and thymol were efficiently loaded onto UiO-66 with loading rates of 79.60 ± 0.71% and 79.65 ± 0.76%, respectively. The release rates of carvacrol and thymol were 77.82 ± 0.87% and 76.51 ± 0.58%, respectively, after a period of 72 h. Moreover, Car@UiO-66 and Thy@UiO-66 demonstrated excellent antibacterial properties against Candida albicans, Escherichia coli, and Staphylococcus aureus with minimum bactericidal concentrations (MBC) of 0.313 mg/mL, 0.313 mg/mL, and 1.25 mg/mL, respectively. Furthermore, based on the results of the CCK8 cytotoxicity assay, even at concentrations as high as 1.25 mg/mL, Car@UiO-66 and Thy@UiO-66 exhibited excellent biocompatibility with a relative cell survival rate above 50%. These findings suggest that Car@UiO-66 and Thy@UiO-66 possess favorable biocompatibility properties without significant toxicity towards periodontal membrane cells. Additionally, in vivo studies confirmed the efficacy of Car@UiO-66and Thy@UiO-66 in reducing inflammation, promoting bone formation through inhibition of TNF-a and IL6 expression, enhancement of IL10 expression, and acceleration of bone defect healing. Therefore, the unique combination of antibacterial, anti-inflammatory, and osteogenic properties make Car@UiO-66 and Thy@Ui O-66 promising candidates for the treatment of oral infectious diseases and repairing bone defects.


Asunto(s)
Antibacterianos , Antiinflamatorios , Candida albicans , Cimenos , Escherichia coli , Estructuras Metalorgánicas , Staphylococcus aureus , Timol , Timol/química , Timol/farmacología , Cimenos/química , Cimenos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Candida albicans/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Ratas , Osteogénesis/efectos de los fármacos , Humanos
3.
Clin Oral Investig ; 28(7): 413, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38965139

RESUMEN

OBJECTIVES: This study compares the biofilm inhibition effects of denture cleaning tablets, carvacrol, and their combined use against Candida albicans on denture bases produced with different techniques. Additionally, the surface roughness and contact angles of these denture bases were evaluated. MATERIALS AND METHODS: Test samples were prepared from four different denture base materials (cold-polymerized, heat-polymerized, CAD/CAM milling, and 3D-printed). The surface roughness and contact angles of the test samples were measured using a profilometer and goniometer, respectively. For the evaluation of biofilm inhibition, samples were divided into 5 subgroups: Corega and carvacrol, separately and combined treatments, positive (inoculated with C. albicans) and negative control (non-inoculated with C. albicans, only medium). Biofilm mass was determined using the crystal violet method. An additional prepared test sample for each subgroup was examined under scanning electron microscopy (SEM). RESULTS: The surface roughness values of the 3D-printed test samples were found to be statistically higher than the other groups (P < .001). The water contact angle of all test materials was not statistically different from each other (P > .001). Corega and carvacrol, separately and combined, significantly decreased the amount of biofilm on all surfaces (P < .0001). Treatment of corega alone and in combination with carvacrol to the 3D-printed material caused less C. albicans inhibition than the other groups (P < .001; P < .05). CONCLUSIONS: The surface roughness values of all test groups were within the clinically acceptable threshold. Although Corega and carvacrol inhibited C. albicans biofilms, their combined use did not show a synergistic effect. CLINICAL RELEVANCE: Carvacrol may be used as one of the disinfectant agents for denture cleaning due to its biofilm inhibition property.


Asunto(s)
Biopelículas , Candida albicans , Cimenos , Bases para Dentadura , Limpiadores de Dentadura , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Bases para Dentadura/microbiología , Cimenos/farmacología , Limpiadores de Dentadura/farmacología , Impresión Tridimensional , Comprimidos
4.
BMC Complement Med Ther ; 24(1): 265, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992651

RESUMEN

BACKGROUND: Origanum species have been used in various commercial constructions as a remedy against burns and wounds, agriculture, alcoholic drinks, fragrance, and flavoring substances of food products. The essential oil of Origanum onites L. (EOOO) and its component carvacrol (CV) possesses a wide range of biological activities including anti-cancer activity. PURPOSE: The purpose of this study was to investigate the growth inhibitory activity of the essential oil and its major component CV and then hepatotoxicity pathway-related genes in HepG2 cells. METHODS: The effects of the EOOO and CV on cell growth and mRNA expressions of 84 hepatotoxicity pathway-related genes were investigated in HepG2, using trypan blue exclusion/ bromodeoxyuridine (BrdU) incorporation tests and real-time-polymerase chain reaction (RT-PCR) array, respectively. RESULTS: The EOOO and CV inhibited cell growth with IC50 values of 0.08 µg/mL and 45 µg/mL, respectively, after 24 h. Real-time, reverse-transcription-polymerase chain reaction (RT2-PCR) array analysis revealed that expressions of 32 genes out of 84 were changed at least 2-fold or more in the EOOO-treated cells. Among them, expression levels of 17 genes were elevated, while expression levels of 15 genes were diminished. Furthermore, after exposure of cells to 45 µg/mL of CV, the expression of 8 genes was increased while the other 8 genes were decreased. Both the EOOO and carvacrol affected the expression of 48 genes of HepG2 cells which are involved in the hepatotoxicity pathway, indicating their hepatoprotective and possible anti-hepatocarcinogenic effects. CONCLUSION: The present study demonstrates that the essential oil of Origanum onites and carvacrol can be used in various applications such as anticancer or herbal drugs, since its non-hepatotoxicity.


Asunto(s)
Cimenos , Monoterpenos , Aceites Volátiles , Origanum , Humanos , Cimenos/farmacología , Aceites Volátiles/farmacología , Origanum/química , Células Hep G2 , Monoterpenos/farmacología , Proliferación Celular/efectos de los fármacos
5.
Molecules ; 29(13)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38999167

RESUMEN

Organometallic complexes of the formula [Ru(N^N)(p-cymene)Cl][X] (N^N = bidentate polypyridyl ligands, p-cymene = 1-methyl-4-(1-methylethyl)-benzene, X = counter anion), are currently studied as possible candidates for the potential treatment of cancer. Searching for new organometallic compounds with good to moderate cytotoxic activities, a series of mononuclear water-soluble ruthenium(II)-arene complexes incorporating substituted pyridine-quinoline ligands, with pending -CH2OH, -CO2H and -CO2Me groups in the 4-position of quinoline ring, were synthesized, for the first time, to study their possible effect to modulate the activity of the ruthenium p-cymene complexes. These include the [Ru(η6-p-cymene)(pqhyme)Cl][X] (X = Cl- (1-Cl), PF6- (1-PF6), pqhyme = 4-hydroxymethyl-2-(pyridin-2-yl)quinoline), [Ru(η6-p-cymene)(pqca)Cl][Cl] ((2-Cl), pqca = 4-carboxy-2-(pyridin-2-yl)quinoline), and [Ru(η6-p-cymene)(pqcame)Cl][X] (X = Cl- (3-Cl), PF6- (3-PF6), pqcame = 4-carboxymethyl-2-(pyridin-2-yl)quinoline) complexes, respectively. Identification of the complexes was based on multinuclear NMR and ATR-IR spectroscopic methods, elemental analysis, conductivity measurements, UV-Vis spectroscopic, and ESI-HRMS techniques. The solid-state structures of 1-PF6 and 3-PF6 have been elucidated by single-crystal X-ray diffraction revealing a three-legged piano stool geometry. This is the first time that the in vitro cytotoxic activities of these complexes are studied. These were conducted in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) via the MTT assay. The results show poor in vitro anticancer activities for the HeLa cancer cell lines and 3-Cl proved to be the most potent (IC50 > 80 µΜ). In both cell lines, the cytotoxicity of the ligand precursor pqhyme is significantly higher than that of cisplatin.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Cimenos , Piridinas , Quinolinas , Rutenio , Humanos , Rutenio/química , Quinolinas/química , Quinolinas/síntesis química , Quinolinas/farmacología , Ligandos , Cimenos/química , Cimenos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Piridinas/química , Piridinas/síntesis química , Piridinas/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Estructura Molecular , Línea Celular Tumoral , Cristalografía por Rayos X , Supervivencia Celular/efectos de los fármacos
6.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-39000327

RESUMEN

Microbial biofilms pose severe problems in the medical field and food industry, as they are the cause of many serious infections and food-borne diseases. The extreme biofilms' resistance to conventional anti-microbial treatments presents a major challenge to their elimination. In this study, the difference in resistance between Staphylococcus aureus DSMZ 12463 biofilms, biofilm-detached cells, and planktonic cells against microcapsules containing carvacrol was assessed. The antimicrobial/antibiofilm activity of low pH disinfection medium containing the microencapsulated carvacrol was also studied. In addition, the effect of low pH on the in vitro carvacrol release from microcapsules was investigated. The minimum inhibitory concentration of microencapsulated carvacrol was 0.625 mg mL-1. The results showed that biofilms exhibited greater resistance to microencapsulated carvacrol than the biofilm-detached cells and planktonic cells. Low pH treatment alone, by hydrochloric acid addition, showed no bactericidal effect on any of the three states of S. aureus strain. However, microencapsulated carvacrol was able to significantly reduce the planktonic cells and biofilm-detached cells below the detection limit (no bacterial counts), and the biofilm by approximatively 3 log CFU mL-1. In addition, results showed that microencapsulated carvacrol combined with low pH treatment reduced biofilm by more than 5 log CFU mL-1. Thus, the use of microencapsulated carvacrol in acidic environment could be a promising approach to combat biofilms from abiotic surfaces.


Asunto(s)
Antibacterianos , Biopelículas , Cimenos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Biopelículas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Cimenos/farmacología , Concentración de Iones de Hidrógeno , Antibacterianos/farmacología , Plancton/efectos de los fármacos , Cápsulas , Composición de Medicamentos/métodos , Farmacorresistencia Bacteriana/efectos de los fármacos
7.
Sci Rep ; 14(1): 13951, 2024 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886531

RESUMEN

The thrust of the study was to determine the chemical composition of the essential oils extracted from Thymus pallescens de Noé and Cymbogon citratus Stapf. as well as to evaluate their efficacy in controlling Sitophilus zeamais Motschulsky and Tribolium castaneum (Herbst) in either single or combined populations. Carvacrol (56.04%) and geraniol (20.86%) were identified as the major constituents of T. pallescens and C. citratus respectively. The tested essential oils showed pronounced insecticidal activity against the pest species in relation with the applied doses. T. pallescens EO had the highest efficacy and S. zeamais was found to be more susceptible to both individual and combined treatments. With reference to the contact and fumigation assessments, T. pallescens EO effectuated corrected mortality rates ranging from 42.5-100% to 25-100% in S. zeamais with corresponding lethal concentration (LC50) values of 17.7 µl/ml and 15µL/L air respectively. Whereas, the T. pallescens EO exhibited corrected mortality rates of 42.5-100% and 20-100% with corresponding LC50 values of 18.1 µl/ml and 15.5 µL/L air against T. castaneum in contact and fumigation assessments, respectively. The corrected mortality rates increased for both insect species when using combination treatments, with significant increases in the LC50 values, ranging from 8.59 to 49.9% for both pest species. Analysis of energy biomarkers in the treated insects indicate significantly increased protein and carbohydrate contents and decreased lipids levels. The study therefore demonstrated the bio-insecticidal toxicity of the EOs from T. pallescens and C. citratus against two important maize post-harvest pests, concurrently revealing significant positive and negative insecticidal activity gradients in relation to single or combined populations.


Asunto(s)
Insecticidas , Aceites Volátiles , Thymus (Planta) , Tribolium , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Tribolium/efectos de los fármacos , Insecticidas/farmacología , Insecticidas/química , Thymus (Planta)/química , Monoterpenos Acíclicos/farmacología , Monoterpenos Acíclicos/química , Gorgojos/efectos de los fármacos , Cimenos/farmacología , Cimenos/química
8.
Bioorg Med Chem Lett ; 109: 129826, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38830427

RESUMEN

Carvacrol, called CA, is a dynamic phytoconstituent characterized by a phenol ring abundantly sourced from various natural reservoirs. This versatile scaffold serves as a pivotal template for the design and synthesis of novel drug molecules, harboring promising biological activities. The active sites positioned at C-4, C-6, and the hydroxyl group (-OH) of CA offer fertile ground for creating potent drug candidates from a pharmacological standpoint. In this comprehensive review, we delve into diverse synthesis pathways and explore the biological activity of CA derivatives. We aim to illuminate the potential of these derivatives in discovering and developing efficacious treatments against a myriad of life-threatening diseases. By scrutinizing the structural modifications and pharmacophore placements that enhance the activity of CA derivatives, we aspire to inspire the innovation of novel therapeutics with heightened potency and effectiveness.


Asunto(s)
Cimenos , Descubrimiento de Drogas , Cimenos/química , Cimenos/farmacología , Cimenos/síntesis química , Humanos , Estructura Molecular , Animales , Relación Estructura-Actividad , Monoterpenos/química , Monoterpenos/farmacología , Monoterpenos/síntesis química
9.
Molecules ; 29(12)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38930942

RESUMEN

Naturally occurring substances and their derivatives function as vital resources for pesticides that can be used in fields, such as insecticide production and fungicide development. As a botanical entity displaying multifaceted biological functions, wormwood has received thorough scrutiny across multiple sectors. The insect repellency potency combined with antibacterial and antifungal activities of wormwood position it as a potential candidate for prospective development into eco-friendly chemical pesticides. In this research, Wormwood essential oil was procured via ethanol water under ultrasonic scenarios and subsequently diluted with PEG 400 to formulate green chemical pesticides. The defensive efficacy of this green pesticide on plants was validated through 2 weeks of clustered plant growth experiments. Active constituents that exerted their effects were scrutinized by GC-MS. Furthermore, this green pesticide also displays efficacious effects on the prevention and management of aphids, exhibiting a dose-dependent relationship. 4-terpenol, eucalyptol, carvacrol, and L-borneol were identified by GC-MS as the predominant active constituents in this green chemical pesticide. Wormwood can be leveraged to develop green chemical pesticides, which can protect plants without contaminating the environment.


Asunto(s)
Insecticidas , Aceites Volátiles , Insecticidas/química , Insecticidas/farmacología , Animales , Aceites Volátiles/química , Aceites Volátiles/farmacología , Cromatografía de Gases y Espectrometría de Masas , Cimenos/química , Cimenos/farmacología , Tecnología Química Verde/métodos , Áfidos/efectos de los fármacos , Eucaliptol/química , Eucaliptol/farmacología , Canfanos
10.
Arch Biochem Biophys ; 758: 110062, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38880320

RESUMEN

Carvacrol (CV) is an organic compound found in the essential oils of many aromatic herbs. It is nearly unfeasible to analyze all the current human proteins for a query ligand using in vitro and in vivo methods. This study aimed to clarify whether CV possesses an anti-diabetic feature via Docking-based inverse docking and molecular dynamic (MD) simulation and in vitro characterization against a set of novel human protein targets. Herein, the best poses of CV docking simulations according to binding energy ranged from -7.9 to -3.5 (kcal/mol). After pathway analysis of the protein list through GeneMANIA and WebGestalt, eight interacting proteins (DPP4, FBP1, GCK, HSD11ß1, INSR, PYGL, PPARA, and PPARG) with CV were determined, and these proteins exhibited stable structures during the MD process with CV. In vitro application, statistically significant results were achieved only in combined doses with CV or metformin. Considering all these findings, PPARG and INSR, among these target proteins of CV, are FDA-approved targets for treating diabetes. Therefore, CV may be on its way to becoming a promising therapeutic compound for treating Diabetes Mellitus (DM). Our outcomes expose formerly unexplored potential target human proteins, whose association with diabetic disorders might guide new potential treatments for DM.


Asunto(s)
Cimenos , Hipoglucemiantes , Metformina , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Monoterpenos , Humanos , Cimenos/farmacología , Cimenos/química , Metformina/farmacología , Metformina/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Monoterpenos/farmacología , Monoterpenos/química , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Receptor de Insulina/metabolismo , PPAR gamma/metabolismo , PPAR gamma/química , Unión Proteica , Simulación por Computador , Antígenos CD
11.
Nat Commun ; 15(1): 4943, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858372

RESUMEN

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.


Asunto(s)
Benzoquinonas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Staphylococcus aureus , Benzoquinonas/química , Benzoquinonas/farmacología , Benzoquinonas/metabolismo , Fármacos Fotosensibilizantes/farmacología , Animales , Ratones , Femenino , Fotoquimioterapia/métodos , Transporte de Electrón/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Cimenos/farmacología , Cimenos/química , Antibacterianos/farmacología , Oxígeno Singlete/metabolismo , Superóxidos/metabolismo , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Luz , Ratones Endogámicos BALB C
12.
Exp Eye Res ; 244: 109938, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38789020

RESUMEN

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.


Asunto(s)
Supervivencia Celular , Cimenos , Modelos Animales de Enfermedad , Degeneración Retiniana , Células Ganglionares de la Retina , Animales , Conejos , Degeneración Retiniana/prevención & control , Degeneración Retiniana/patología , Degeneración Retiniana/metabolismo , Cimenos/farmacología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Inyecciones Intravítreas , Citometría de Flujo , Reflejo Pupilar/efectos de los fármacos , Reflejo Pupilar/fisiología
13.
J Antibiot (Tokyo) ; 77(7): 436-453, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38750249

RESUMEN

Mixed vaginitis due to bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) is the most prevalent form and presents a significant therapeutic challenge globally. Since, the administration of monotherapy leads to subsequent recurrent infections, synergistic therapy that completely eradicates both pathogens is of dire need to manage mixed vaginities scenario and to prevent its recurrence. The current investigation was focused on exploring the synergistic inhibitory efficacy of phytochemicals against the virulence traits of individual and mixed species of C. albicans and G. vaginalis in vitro and in vivo (Galleria mellonella). Out of five phytochemicals (carvacrol, thymol, cinnamaldehyde, eugenol, and borneol) screened for synergism with citral [(Ct) as the prime molecule owing to its myriad therapeutic potential], carvacrol (Ca) in combination with citral exhibited promising synergistic effect. Time-kill kinetics and one-minute contact-killing assays demonstrated the phenomenal microbicidal effect of Ct-Ca combination against both mono and dual-species within 30 min and one-minute time intervals, respectively. Furthermore, the sub-CMICs (synergistic combinatorial MIC) of Ct-Ca have significantly eradicated the mature biofilms and remarkably reduced the virulence attributes of both C. albicans and G. vaginalis (viz., yeast to hyphae transition, filamentation, protease production, and hydrophobicity index), in single and dual species states. The non-toxic nature of Ct-Ca combination was authenticated using in vitro (human erythrocyte cells) and in vivo (Galleria mellonella) models. In addition, the in vivo efficacy evaluation and subsequent histopathological investigation was done using the invertebrate model system G. mellonella, which further ascertained the effectiveness of Ct-Ca combination in fighting off the infection caused by individual and mixed species of C. albicans and G. vaginalis. Concomitantly, the current work is the first of its kind to delineate the in vitro interaction of C. albicans and G. vaginalis mixed species at their growth and biofilm states, together emphasizes the promising therapeutic potential of acclaimed phytochemicals as combinatorial synergistic therapy against mixed vaginitis.


Asunto(s)
Monoterpenos Acíclicos , Candida albicans , Candidiasis Vulvovaginal , Cimenos , Sinergismo Farmacológico , Gardnerella vaginalis , Candida albicans/efectos de los fármacos , Candida albicans/patogenicidad , Femenino , Cimenos/farmacología , Animales , Monoterpenos Acíclicos/farmacología , Gardnerella vaginalis/efectos de los fármacos , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/microbiología , Virulencia/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Mariposas Nocturnas/microbiología , Monoterpenos/farmacología , Antifúngicos/farmacología , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Humanos , Biopelículas/efectos de los fármacos
14.
Food Res Int ; 187: 114458, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763690

RESUMEN

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.


Asunto(s)
Antibacterianos , Biopelículas , Pollos , Cimenos , Flavonoides , Microbiología de Alimentos , Pruebas de Sensibilidad Microbiana , Salmonella typhimurium , Biopelículas/efectos de los fármacos , Cimenos/farmacología , Salmonella typhimurium/efectos de los fármacos , Flavonoides/farmacología , Antibacterianos/farmacología , Animales , Percepción de Quorum/efectos de los fármacos , Carne/microbiología , Monoterpenos/farmacología , Microscopía Electrónica de Rastreo
15.
Cell Biochem Funct ; 42(4): e4062, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38807490

RESUMEN

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.


Asunto(s)
Antineoplásicos , Apoptosis , Neoplasias de la Mama , Cimenos , Puntos Cuánticos , Óxido de Zinc , Humanos , Puntos Cuánticos/química , Óxido de Zinc/química , Óxido de Zinc/farmacología , Óxido de Zinc/síntesis química , Cimenos/farmacología , Cimenos/química , Concentración de Iones de Hidrógeno , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Femenino , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos
16.
Molecules ; 29(10)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38792138

RESUMEN

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.


Asunto(s)
Antibacterianos , Antineoplásicos , Cimenos , Timol , Timol/química , Timol/farmacología , Cimenos/química , Cimenos/farmacología , Cimenos/uso terapéutico , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Relación Estructura-Actividad , Neoplasias/tratamiento farmacológico , Animales
17.
Int J Food Microbiol ; 418: 110713, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38718617

RESUMEN

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.


Asunto(s)
Antibacterianos , Quitosano , Cimenos , Películas Comestibles , Emulsiones , Embalaje de Alimentos , Listeria monocytogenes , Monoterpenos , Salmonella typhimurium , Cimenos/farmacología , Quitosano/farmacología , Quitosano/química , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrollo , Emulsiones/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Embalaje de Alimentos/métodos , Monoterpenos/farmacología , Rosmarinus/química , Pruebas de Sensibilidad Microbiana , Microbiología de Alimentos , Productos de la Carne/microbiología , Conservación de Alimentos/métodos
18.
Biochim Biophys Acta Biomembr ; 1866(5): 184332, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740123

RESUMEN

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.


Asunto(s)
Membrana Celular , Cimenos , Rutenio , Cimenos/química , Cimenos/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/química , Rutenio/química , Rutenio/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Monoterpenos/química , Monoterpenos/farmacología , 1,2-Dipalmitoilfosfatidilcolina/química , Antineoplásicos/química , Antineoplásicos/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Fosfatidilcolinas/química
19.
Asian Pac J Cancer Prev ; 25(5): 1663-1671, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38809638

RESUMEN

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.


Asunto(s)
Apoptosis , Cimenos , Emulsiones , Melanoma , Aceites Volátiles , Extractos Vegetales , Humanos , Emulsiones/química , Melanoma/tratamiento farmacológico , Melanoma/patología , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Cimenos/farmacología , Aceites Volátiles/farmacología , Aceites Volátiles/química , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Células Tumorales Cultivadas , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos
20.
Biomed Pharmacother ; 175: 116692, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38701569

RESUMEN

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.


Asunto(s)
Benzaldehídos , Benzoquinonas , Tetracloruro de Carbono , Ácido Gálico , Riñón , Pulmón , FN-kappa B , Estrés Oxidativo , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Ácido Gálico/farmacología , Benzoquinonas/farmacología , Transducción de Señal/efectos de los fármacos , Masculino , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratas , Tetracloruro de Carbono/toxicidad , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Benzaldehídos/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Simulación del Acoplamiento Molecular , Cimenos/farmacología , Sustancias Protectoras/farmacología , Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Ratas Wistar , Ratas Sprague-Dawley
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