Effect of Carvacrol on the Biological Behavior of Leukemia Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of carvacrol on the biological behavior of leukemia cells and its regulation to circ-0008717/miR-217 molecular axis.@*METHODS@#Human acute lymphoblastic leukemia cells Molt-4 were cultured in vitro, and different concentrations of carvacrol were added to the cells. si-NC and si-circ-0008717 were transfected into Molt-4 cells (si-NC group, si-circ-0008717 group). pcDNA, pcDNA-circ-0008717, anti-miR-NC, anti-miR-217 were transfected into Molt-4 cells and then added to carvacrol-treated cells (carvacrol+pcDNA group, carvacrol+pcDNA-circ-0008717 group, carvacrol+anti-miR-NC group, carvacrol+anti-miR-217 group). MTT, plate clone formation experiment, and flow cytometry were used to detect the viability of the cell, colony formation number, and apoptosis rate of cells, respectively. The RT-qPCR method was used to detect the expression levels of circ-0008717 and miR-217. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ-0008717 and miR-217.@*RESULTS@#After carvacrol treatment, the cell viability decreased significantly (r=-0.9405), expression level of circ-0008717 decreased (r=-0.9117), colonies formed number decreased (r=-0.9256), while the cell apoptosis rate increased (r= 0.8464), and the expression level of miR-217 increased (r=0.9468). Compared with the si-NC group, the expression level of miR-217 in si-circ-0008717 group increased (P＜0.001), the cell apoptosis rate increased (P＜0.001), while cell viability decreased (P＜0001), the number of colonies formed decreased (P＜0.001). Compared with the carvacrol+pcDNA group, the cell viability of the carvacrol+pcDNA-circ-0008717 group increased (P＜0.001), the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0.001). circ-0008717 could target miR-217. The cell viability of the carvacrol+anti-miR-217 group increased (P＜0.001), and the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0001) as compared with the carvacrol+anti-miR-NC group.@*CONCLUSION@#Carvacrol can promote the expression of miR-217 by down-regulating the expression of circ-0008717, thereby reducing the proliferation and cloning ability of leukemia cells and promoting cell apoptosis.

Effects of carvacrol and physical exercise on motor and memory impairments associated with Parkinson's disease / Efeitos do carvacrol e do exercício físico sobre o comprometimento motor e de memória associados à doença de Parkinson

ABSTRACT The present study was undertaken to investigate the effects of carvacrol and treadmill exercise on memory deficit, rotational behavior and oxidative stress biomarkers in a 6-OHDA-lesioned rat model of Parkinson's disease. Wistar rats were treated with carvacrol at a dose of 25 mg/kg and/or ran on a treadmill for a week. Then, 6-OHDA was microinjected into the medial forebrain bundle and treatments continued for six more weeks. Aversive memory, rotational behavior and oxidative stress biomarkers were assessed at the end of week six. The 6-OHDA-lesioned group showed a significant increase in rotational behavior and a decrease in step-through latency in the passive avoidance test compared with the sham group. These behaviors were accompanied by increased lipid peroxidation levels and decreased total thiol concentration in the striatum and/or hippocampus of the hemiparkinsonian rats. Moreover, treatment with carvacrol and exercise reduced rotational behavior and improved aversive memory deficit, which was accompanied by decreased lipid peroxidation levels and increased total thiol concentration in the striatum and/or hippocampus. In conclusion, treatment with carvacrol and treadmill exercise ameliorated motor and memory deficits by modulating oxidative stress in the striatum and hippocampus of hemiparkinsonian rats. Therefore, the combination of carvacrol and treadmill exercise could be an effective therapeutic tool for treatment of neurobehavioral deficits in Parkinson's disease patients.

RESUMO O presente estudo foi realizado para investigar os efeitos do carvacrol e do exercício em esteira sobre o déficit de memória, comportamento rotacional e biomarcadores de estresse oxidativo em um modelo animal (ratos lesionados por 6-OHDA) da doença de Parkinson (DP). Ratos Wistar foram tratados com carvacrol na dose de 25 mg/kg e/ou correram em uma esteira por uma semana. Depois, 6-OHDA foi microinjetada no feixe do prosencéfalo medial e os tratamentos continuaram por mais seis semanas. A memória aversiva, o comportamento rotacional e biomarcadores de estresse oxidativo foram avaliados no final da semana 6. O grupo 6-OHDA mostrou um aumento significativo no comportamento rotacional e uma diminuição na latência no teste de esquiva passiva em comparação com o grupo "sham". Estes comportamentos foram acompanhados por aumento dos níveis de peroxidação lipídica e diminuição da concentração total de tiol no estriado e/ou hipocampo de ratos hemiparkinsonianos. Além disso, o tratamento com carvacrol e exercício reduziu o comportamento rotacional e melhorou o déficit de memória aversiva, que foi acompanhado pela diminuição dos níveis de peroxidação lipídica e aumento da concentração total de tiol no estriado e/ou hipocampo. Em conclusão, o tratamento com carvacrol e exercícios em esteira melhorou os déficits motor e de memória, modulando o estresse oxidativo no estriado e no hipocampo de ratos hemiparkinsonianos. Portanto, a combinação de carvacrol e exercício em esteira pode ser uma ferramenta terapêutica eficaz para o tratamento de déficits neurocomportamentais em pacientes com DP.

Growth modeling to control (in vitro) Fusarium verticillioides and Rhizopus stolonifer with thymol and carvacrol / Modelización del crecimiento in vitro para controlar Fusarium verticillioides y Rhizopus stolonifer con timol y carvacrol

The aim of this study was to evaluate the antifungal activity (in vitro) of thymol and carvacrol alone or in mixtures against Fusarium verticillioides and Rhizopus stolonifer, and to obtain primary growth models. Minimal inhibitory concentration (MIC) was evaluated with fungal radial growth with thymol or carvacrol concentrations (0-1600mg/l). Mixtures were evaluated using concentrations below MIC values. Radial growth curves were described by the modified Gompertz equation. MIC values of carvacrol were 200mg/l for both fungi. Meanwhile, MIC values of thymol were between 500 and 400mg/l for F verticillioides and R. stolonifer, respectively. A synergistic effect below MIC concentrations for carvacrol (100mg/l) and thymol (100-375 mg/l) was observed. Significant differences (p <0.05) between the Gompertz parameters for the antimicrobial concentrations and their tested mixtures established an inverse relationship between antimicrobial concentration and mycelial development of both fungi. Modified Gompertz parameters can be useful to determine fungistatic concentrations.

El objetivo de este trabajo fue evaluar la actividad antifúngica in vitro del timol y del carvacrol, solos o en mezclas, contra Fusarium verticillioides y Rhizopus stolonifer, y obtener modelos primarios de crecimiento. Se evaluó la concentración inhibitoria mínima (CIM) con el crecimiento radial, se ensayaron concentraciones de timol y carvacrol de 0 a 1.600 mg/l. Las mezclas se evaluaron utilizando concentraciones por debajo de los valores de CIM. Las curvas de crecimiento radial fueron descritas por la ecuación de Gompertz modificada. Se obtuvieron los siguientes valores de CIM: carvacrol, 200 mg/l para las 2 especies; timol, 500 mg/l y 400 mg/l para F. verticillioides y R. stolonifer, respectivamente. Se observó un efecto sinèrgico a concentraciones inferiores a las CIM para el carvacrol (100mg/l) y el timol (100-375 mg/l). Hubo diferencias significativas (p <0,05) entre los parámetros de crecimiento de Gompertz; se estableció que existe una relación inversa entre la concentración de los antimicrobianos y el desarrollo del micelio de ambos hongos.

Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson's disease / O tratamento com carvacrol melhora a memória de esquiva passiva em um modelo da doença de Parkinson em ratos

ABSTRACT The present study investigated the effects of carvacrol on motor and memory deficits as well as hyperalgesia in the 6-OHDA-lesioned rat model of Parkinson's disease. The animals were subjected to unilateral microinjection of 6-OHDA into the medial forebrain bundle and treated with carvacrol (25, 50 and 100 mg/kg, ip) for six weeks after surgery. The 6-OHDA-lesioned rats showed contralateral rotations towards the lesion side, which was accompanied by learning and memory deficits in a passive avoidance test and a decrease in tail withdrawal latency in a tail flick test at the end of week 6. The results also showed that treatment with carvacrol at a dose of 25 mg/kg ameliorated memory deficits, with no effect on rotations and hyperalgesia in lesioned rats. In conclusion, carvacrol improves memory impairments in rats with Parkinson's disease; therefore, it may serve as an adjunct therapy for the alleviation of memory deficits in Parkinson's disease patients.

RESUMO O presente estudo investigou os efeitos do carvacrol nos déficits motores e de memória, bem como na hiperalgesia, em um modelo da doença de Parkinson (DP) em ratos com lesões 6-OHDA. Os animais foram submetidos a microinjeção unilateral de 6-OHDA no feixe mediano do prosencéfalo e tratados com carvacrol (25, 50 e 100 mg / kg, ip) durante 6 semanas após a cirurgia. Os ratos com lesões 6-OHDA mostraram rotações contralaterais para o lado da lesão, que foram acompanhadas de déficits de aprendizagem e de memória em um teste de evitação passiva, e de uma diminuição da latência de retirada da cauda em um teste de cauda no final da semana 6. Os resultados também mostraram que o tratamento crônico com carvacrol a uma dose de 25 mg / kg aliviou os déficits de memória, sem efeito sobre rotações e hiperalgesia em ratos lesados. Em conclusão, o carvacrol melhora a deficiência de memória em ratos com DP e, portanto, pode servir como uma terapia complementar para aliviar os déficits de memória em pacientes com DP.

Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats

OBJECTIVE@#To unravel the mechanism of anti-inflammatory activity of carvacrol in D-galactosamine (D-GalN)-induced hepatotoxic rats.@*METHODS@#The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa-B (NF-κB) were assayed by semi-quantitative reverse transcriptase polymerase chain reaction (RTPCR) and western blot analysis.@*RESULTS@#We found that the mRNA and protein expressions of TNF-α, IL-6, iNOS, COX-2 and NF-κB were significantly up-regulated in D-galactosamine induced hepatotoxic rats and treatment with carvacrol significantly down-regulated the expressions of these genes showing the mechanism behind the anti-inflammatory activity of carvacrol.@*CONCLUSIONS@#All above results reveal that the carvacrol well known anti-inflammatory activities in D-galactosamine induced hepatotoxic rats.

Chemical composition of the essential oils from two subspecies of Protium heptaphyllum / Composição química do óleo essencial de duas subespécies do Protium heptaphyllum

Qualitative and quantitative analyses of the volatile constituents from resin of Protium heptaphyllum (Aubl.) Marchand subsp. ulei (Swat) Daly (PHU), and Protium heptaphyllum (Aubl.) Marchand subsp. heptaphyllum (PHH), Burseraceae were performed using GC-MS and GC-FID. The resins were collected around the city of Cruzeiro do Sul, state of Acre, Brazil. Essential oils from the two subspecies were extracted by hydrodistillation with a yield of 8.6 percent (PHU) and 11.3 percent (PHH); the main components were terpinolene (42.31 percent) and p-cymene (39.93 percent) for subspecies ulei (PHU) and heptaphyllum (PHH), respectively.

As análises qualitativa e quantitativa dos óleos essenciais obtidos das resinas das espécies Protium heptaphyllum (Aubl.) Marchand subespécie ulei (Swat) Daly (PHU) e Protium heptaphyllum (Aubl.) Marchand subespécie heptaphyllum (PHH), Burseraceae, foram realizadas utilizando cromatografia em fase gasosa acoplado a um espectrômetro de massa (CG-EM) e cromatografia a gás com detector de chama (CG-DIC). As resinas foram coletadas no Município de Cruzeiro do Sul, Acre, Brasil. O óleo essencial das oleoresinas foi extraído por hidrodestilação fornecendo rendimento 8,6 por cento para PHU e 11,3 por cento para PHH. Os monoterpenos terpinoleno (42.31 por cento) e p-cimeno (39.93 por cento) foram os constituintes principais para PHU e PHH, respectivamente.