RESUMEN
Artemisia absinthium has long been used traditionally as an anti-microbial and antioxidant agent. Various biologically active secondary metabolites, including phenolic compounds such as gallic acid and p-coumaric acid, have been reported from the species. In addition, growing the plants under in vitro conditions enriched with elicitors is a cost-effective approach to enhance secondary metabolite production. This paper examined microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) effects on morphological characteristics, phenolic compounds, antioxidant activity, and volatile oil content of A. absinthium. The treated shoots with various concentrations of MCC and NCC were subjected to spectrophotometric, GC-MS, and LC-MS analysis. FESEM-EDX, TEM, XRD, and DLS methods were applied to characterize MCC and NCC properties. Morphological findings revealed that the stem length, dry, and fresh weights were improved significantly (P ≤ 0.05) under several MCC and NCC concentrations. Some treatments enhanced gallic and p-coumaric acid levels in the plant. Although 1.5 g/L of MCC treatment showed the highest antioxidant activity, all NCC treatments reduced the antioxidant effect. The findings suggest that both MCC and NCC, at optimized concentrations, could be exploited as elicitors to improve the secondary metabolite production and morphological properties.
Asunto(s)
Antioxidantes , Artemisia absinthium , Ácidos Cumáricos , Antioxidantes/metabolismo , Artemisia absinthium/química , Artemisia absinthium/metabolismo , Celulosa/química , Fenoles/metabolismoRESUMEN
Although all-trans retinoic acid (ATRA) is an efficient pattern in acute promyelocytic leukemia (APL) therapy, further studies are required due to the extant clinical limitations of ATRA. It has been reported that Silymarin, an anti-cancer herbal substance extracted from milk thistle (Silybum marianum), is able to regulate apoptosis in various types of cancer cells through different mechanisms of action. This study investigated the apoptosis-inducing effect of Silymarin (SM) alone and in combination with ATRA on human acute promyelocytic NB4 cells. Examination using MTT assay indicated that SM treatment leads to growth inhibition in NB4 cells in a dose-dependent manner. The IC50 values of SM and ATRA were calculated 90 µM and 2 µM, respectively. Cell cycle analysis by flow cytometry revealed that a more increase in the sub-G1 phase (a sign of apoptosis) when cells were exposed to SM in combination with ATRA. The incidence of apoptosis was confirmed through Hoechst 33258 staining and Annexin V-FITC analysis. The results showed that Silymarin enhances ATRA-induced apoptosis. The flow cytometric analysis also indicated an enhancement in levels of ROS in the treated cells with both compounds. The real-time PCR illustrated that SM targets apoptosis by down-regulation in Survivin and Bcl-2 while up-regulation in Bax. The findings showed that the combination of the two compounds is more effective in the induction of apoptosis in NB4 cells. Molecular docking studies indicated that Sylibin, as a primary compound of the SM, binds to the BH3 domain of Bcl-2 and the BIR domain of Survivin with various affinities. Based on the findings, it seems that SM used alone and in combination with ATRA may be beneficial for inducing apoptosis in APL cells.
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Leucemia Promielocítica Aguda , Silimarina , Humanos , Survivin/farmacología , Silimarina/farmacología , Simulación del Acoplamiento Molecular , Línea Celular Tumoral , Diferenciación Celular , Tretinoina/farmacología , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
Reduced graphene oxide (rGO) and Mg/rGO nanocomposites (NCs) were prepared by an eco-friendly technique using Rosa canina fruit extract. Physicochemical properties and cytotoxicity to Mentha longifolia in vitro cultures of these nanomaterials were examined by using XRD, FESEM, EDX, FT-IR, DLS/zeta potential, UV-Visible, and GC-MS techniques. The characterization techniques confirmed the synthesis of rGO and Mg/rGO NCs with particle sizes less than 20 nm (based on FESEM). In accordance to the biological measurements, rGO showed in vitro cytotoxicity to M. longifolia shoot cultures. Mg/rGO NCs showed no significant difference in the growth parameters except for a decrease in the shoot number at the concentrations of 50 and 150 mg/L and a decrease in the length of the tallest root at the concentrations of 100 and 150 mg/L, however efficiently improved the photosynthetic pigment contents. The phytochemical assay depicted that the total content of volatile compounds was increased in the treated cultures with 25, 50, and 100 mg/L of rGO and Mg/rGO NCs in comparison to the control. Generally, the more oxygenated and hydrocarbon sesquiterpenes were observed in the cultures treated with 25 and 100 mg/L of rGO and 25 and 50 mg/L of Mg/rGO NCs.
Asunto(s)
Grafito , Mentha , Nanocompuestos , Grafito/química , Grafito/toxicidad , Nanocompuestos/química , Nanocompuestos/toxicidad , Fitoquímicos , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Although doping of various rare earth elements such as samarium on zinc oxide nanoparticles (ZnO NPs) can noticeably improve their photocatalytic performance, it may enhance their toxicity to living organisms. Thus, the toxic impacts of samarium-doped ZnO NPs (Sm/ZnO NPs) on different organisms should be carefully evaluated. In this study, an eco-toxicological experimentation system using the green microalga Chlorella vulgaris was established to determine the potential toxicity of ZnO and Sm/ZnO NPs synthesized by polymer pyrolysis method. Accordingly, growth parameters, oxidative stress biomarkers, and morphological features of the algal cells were analyzed. Both ZnO and Sm/ZnO NPs induced a concentration-dependent cytotoxicity by reducing the cell growth, decreasing photosynthetic pigment contents, and causing deformation in the cellular morphology. Moreover, generation of excessive H2O2, increased activity of superoxide dismutase and ascorbate peroxidase, and reduction in total phenolic and flavonoid contents were observed. Catalase activity was inversely influenced by the NPs in a way that its activity significantly increased at the concentrations of 20 and 25 mg L-1 of ZnO NPs, but was lessened by all supplemented dosages (5-25 mg L-1) of Sm/ZnO NPs. Altogether, the obtained results revealed that Sm-doping can play a significant role in ZnO NP-induced toxicity on C. vulgaris cells.
Asunto(s)
Chlorella vulgaris , Microalgas , Nanopartículas , Óxido de Zinc , Peróxido de Hidrógeno , Nanopartículas/toxicidad , Samario , Zinc , Óxido de Zinc/toxicidadRESUMEN
Callus initiation, shoot formation and plant regeneration were established for Artemisia spicigera, a traditional medicinal plant growing in Armenia, Middle-Anatolia and Iran, and producing valuable volatile organic compounds (VOCs) that are mostly represented by monoterpenoids. Optimal callus initiation and shoot production were obtained by culture of hypocotyl and cotyledon explants on MS medium comprising 0.5 mg L-1 naphthalene acetic acid (NAA) and 0.5 mg L-1 6-benzyladenine (BA). Consequently, the shoots were transferred onto the MS media supplemented with 1 mg L-1 of indole-3-butyric acid (IBA) or 1 mg L-1 of NAA. Both types of auxin induced root formation on the shoots and the resulting plantlets were successfully grown in pots. The production of VOCs in callus tissues and regenerated plantlets was studied by gas chromatography-mass spectrometry (GC-MS) analysis. Although the potential of undifferentiated callus to produce VOCs was very low, an increased content of bioactive volatile components was observed at the beginning of shoot primordia differentiation. Intriguingly, the volatiles obtained from in vitro plantlets showed quantitative and qualitative variation depending on the type of auxins used for the rooting process. The acquired quantities based on total ion current (TIC) showed that the regenerated plantlets using 1 mg L-1 NAA produced higher amounts of oxygenated monoterpenes such as camphor (30.29%), cis-thujone (7.07%), and 1,8-cineole (6.71%) and sesquiterpene derivatives, namely germacrene D (8.75%), bicyclogermacrene (4.0%) and spathulenol (1.49%) compared with the intact plant. According to these findings, in vitro generation of volatile organic compounds in A. spicigera depends on the developmental stages of tissues and may enhance with the formation of shoot primordia and regeneration of plantlets.
RESUMEN
AIMS: Mild traumatic brain injury (mTBI) is an important risk factor for cognitive impairment. Despite intense efforts to develop efficient treatments, the current therapies are not often effective and far from satisfactory. Silymarin has been suggested as a therapeutic agent in the treatment of traumatic brain injury. This study aimed to determine whether silymarin can exert neuroprotective effects on memory impairment following mTBI in mice. MAIN METHODS: After mTBI induction, mice were treated with silymarin once daily for 20 consecutive days by oral gavage. To investigate cognitive functions, animals were subjected to Y-maze, novel-object recognition, and Morris-water maze. Levels of tumor necrosis factor (TNF)-α, glutamate, and brain derived neurotrophic factor (BDNF) were measured in the hippocampus. KEY FINDINGS: Our findings showed that mTBI resulted in a significant decline in memory in the Y-maze and Morris-water maze in both sexes, whereas only impaired cognitive function in males in the novel-object recognition. We found notable increases in TNF-α and glutamate levels in the hippocampus of both sexes, while there was only a significant decrease in hippocampal BDNF in mTBI-induced females. In addition, silymarin treatment improved cognitive impairments in mTBI-induced males but not in females. Silymarin significantly reduced TNF-α and glutamate levels, and increased BDNF levels in the hippocampus of mTBI-induced male but not in female mice. SIGNIFICANCE: This study demonstrates that silymarin treatment sex-dependently improves cognitive impairment in mTBI-induced mice, and suggests that silymarin may be a therapeutic agent for cognitive decline following mTBI in males. Further studies are needed to establish the validity of these findings in humans.
Asunto(s)
Conmoción Encefálica/tratamiento farmacológico , Cognición/efectos de los fármacos , Silimarina/uso terapéutico , Animales , Animales no Consanguíneos , Conmoción Encefálica/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cognición/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Ácido Glutámico/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Factores Sexuales , Silimarina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The increased applications of nanomaterials in industry and biomedicine have resulted in a rising concern about their possible toxic impacts on living organisms. It has been claimed that the phytosynthesized nanomaterials have lower toxicity in comparison to their chemically synthesized counterparts. Therefore, it is important to evaluate their toxic effects on the environment. In the present study, we investigated the toxic effects of microwave-synthesized silver-reduced graphene oxide nanocomposites (MS-Ag-rGO) on Chlorella vulgaris. Algal cells were treated by 1, 2, 4 and 6 mg L-1 MS-Ag-rGO for 24 h. The obtained data with three replicates were examined using analysis of variance. Analysis of different growth parameters revealed that MS-Ag-rGO possessed significant dose-dependent toxic effect on C. vulgaris. Scanning electron microscope and fluorescence microscope images of the treated cells established morphological shrinkages and alteration in position of nucleoli. Moreover, reduction in the phenol and flavonoid contents, enhancement of H2O2 content, changes in the antioxidant enzymes activity and decreases in the growth parameters as well as photosynthetic pigments quantities confirmed the toxicity of MS-Ag-rGO to the C. vulgaris cells. Our findings revealed that MS-Ag-rGO possessed higher toxicity on C. vulgaris than Ag-rGO synthesized by hydrothermal technique.
Asunto(s)
Chlorella vulgaris/efectos de los fármacos , Grafito/toxicidad , Microalgas/efectos de los fármacos , Microondas , Nanocompuestos/toxicidad , Plata/toxicidad , Chlorella vulgaris/ultraestructura , Relación Dosis-Respuesta a Droga , Grafito/química , Tecnología Química Verde , Peróxido de Hidrógeno/metabolismo , Microalgas/ultraestructura , Nanocompuestos/química , Óxidos , Plata/química , Compuestos de PlataRESUMEN
SnO2 nanoparticles (NPs) are promising materials for electrochemical, catalytic, and biomedical applications due to their high photosensitivity, suitable stability characteristics, wide band gap energy potential, and low cost. Doping SnO2 NPs with metallic elements such as Ag has been used to improve their efficiency. Despite their commercial importance, the current literature lacks investigations to determine their toxic effects on plant systems. In this study, SnO2 and Ag/SnO2 NPs were synthesized using polymer pyrolysis method and characterized by means of XRD, TEM, SEM, EDX, and DLS techniques. Subsequently, the toxicity of the synthesized NPs on cell viability, cell proliferation, and a number of oxidative stress markers were measured in tobacco cell cultures. SnO2 and Ag/SnO2 NPs were found to be polygonal in shape with the size range of 10-30â¯nm. Both NPs induced cytotoxicity by reducing the cell viability and cell proliferation in a dose-dependent manner. Furthermore, the generation of H2O2, phenolics, flavonoids, and increased activities of superoxide dismutase (SOD) and peroxidase (POD) were observed. According to the results, Ag-doping played a key role in the induction of toxicity in tobacco cell cultures. The obtained results confirmed that SnO2 and Ag/SnO2 NPs induced cytotoxicity in tobacco cells through oxidative stress.
Asunto(s)
Nanopartículas/toxicidad , Nicotiana/efectos de los fármacos , Células Vegetales/efectos de los fármacos , Plata/toxicidad , Compuestos de Estaño/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Nanopartículas/química , Estrés Oxidativo/efectos de los fármacos , Plata/química , Compuestos de Estaño/químicaRESUMEN
Green algae are dominant primary producers in aquatic environments. Thus, assessing the influences of pollutants such as nanoparticles on the algae is of high ecological significance. In the current study, cadmium selenide nanoparticles (CdSe NPs) were synthesized using the hydrothermal method and their characteristics were determined by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FT-IR) techniques. Subsequently, the toxicity of synthesized nanoparticles on the green microalga Chlorella vulgaris was investigated. The observations by SEM confirmed that exposure to CdSe NPs had severe impacts on the algal morphology. Furthermore, the obtained results revealed the toxic effect of CdSe NPs by a decrease in the number of cells. Measurement of antioxidant enzymes activity showed an increase in the activity of catalase, and a decrease in the activity of superoxide dismutase (SOD) at high concentrations of CdSe NPs. The exposure of C. vulgaris to CdSe NPs resulted also in a change in algal pigments as well as total phenol content. Taken together, CdSe NPs appeared to have significant cytotoxic effects on C. vulgaris in the applied concentrations.
Asunto(s)
Antioxidantes/metabolismo , Compuestos de Cadmio/toxicidad , Chlorella vulgaris/efectos de los fármacos , Nanopartículas/toxicidad , Compuestos de Selenio/toxicidad , Compuestos de Cadmio/química , Catalasa/metabolismo , Chlorella vulgaris/enzimología , Chlorella vulgaris/crecimiento & desarrollo , Nanopartículas/química , Tamaño de la Partícula , Compuestos de Selenio/química , Superóxido Dismutasa/metabolismo , Propiedades de SuperficieRESUMEN
In this work, biological synthesis of MgO/perlite nanocomposites (NCs) besides their effects on morphology and secondary metabolite profiles of Melissa officinalis plant organ cultures were evaluated. MgO NPs were immobilized on the surface of nanoperlite using M. officinalis extract as a capping agent. The as-synthesized MgO/perlite NCs were characterized by using FTIR, XRD, SEM, EDS and DLS. The average particle size of nanoperlite and MgO/perlite NCs was about 10 and 30â¯nm, respectively. Morphological observations showed that nanoperlite and MgO/perlite NCs had no effect on root number, as well as root and shoot length. None of the applied concentrations of perlite and MgO/perlite NCs could significantly increase the growth parameters in comparison to the control, except for 150â¯mg/L of nanoperlite which caused an increase in the shoot number. Although, the contents of chlorophyll and carotenoids were not affected, the maximum content of volatile compounds obtained at 100 of MgO/perlite NCs. Rosmarinic acid was detected in shoots, which treated with 25-100â¯mg/L of perlite and 25, 50 and 150â¯mg/L of MgO/perlite NCs. Our results provided the evidence that nanoperlite and MgO/perlite NCs at specific levels may act as a novel elicitor for in vitro biosynthesis of valuable secondary metabolites.
Asunto(s)
Óxido de Aluminio/metabolismo , Óxido de Magnesio/metabolismo , Melissa/metabolismo , Nanocompuestos , Dióxido de Silicio/metabolismo , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Melissa/crecimiento & desarrolloRESUMEN
Mild traumatic brain injury (mTBI) is a major public health risk for developing anxiety-related disorders and hypothalamus-pituitary-adrenal (HPA) axis dysregulation in humans. Extensive research has shown that dietary intake or supplementation of the natural flavonoid quercetin might be useful for treating anxiety-related symptoms. The objectives of this study were to determine whether quercetin treatment can attenuate anxiogenic-like behaviors and normalize HPA axis function in mice with mTBI. Animals subjected to mTBI were treated daily with quercetin (50 mg/kg) or diazepam (positive control, 3 mg/kg) for 14 days. Four behavioral tests (open field, plus maze, light-dark box, and zero maze) were used to assess anxiety-related behaviors in mice. To evaluate HPA axis function, adrenocorticotropic hormone and corticosterone were measured in the serum of mice after the anxiety tests. Quercetin treatment was found to significantly reduce anxiety-like behaviors in mTBI-induced mice. A strength of this study is the consistency of results among anxiety tests. The dysregulation of the HPA axis in mTBI-induced mice treated with quercetin was also attenuated, with decreased levels of adrenocorticotropic hormone and corticosterone. The effects of quercetin were comparable with those of diazepam treatment. Taken together, these results suggest that quercetin might be useful for treating anxiety-related symptoms and HPA axis hyperreactivity in patients with mTBI.
Asunto(s)
Ansiedad/tratamiento farmacológico , Conmoción Encefálica/tratamiento farmacológico , Quercetina/farmacología , Hormona Adrenocorticotrópica/análisis , Hormona Adrenocorticotrópica/sangre , Animales , Trastornos de Ansiedad/tratamiento farmacológico , Corticosterona/análisis , Corticosterona/sangre , Hormona Liberadora de Corticotropina/metabolismo , Depresión/fisiopatología , Diazepam/farmacología , Modelos Animales de Enfermedad , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Ratones , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Quercetina/metabolismo , Estrés Psicológico/fisiopatologíaRESUMEN
Recent studies have shown that mild traumatic brain injury (mTBI) is associated with higher risk for anxiety-related disorders. Dysregulation in the hypothalamus-pituitary-adrenal (HPA) axis following mTBI has been proposed to be involved in the development of neurobehavioral abnormalities; however, the underlying mechanisms are largely unknown. The aim of this study was to determine whether the corticotropin-releasing-factor-1 (CRF-1) receptor is involved in the regulation of anxiety-related symptoms in a mouse model of mTBI. Animals with or without mTBI received intracerebroventricular injections of a CRF-1 receptor agonist (CRF; 0.01 nmol/mouse) or antagonist (antalarmin; 1 µg/mouse) for 5 days, and then the animals were subjected to anxiety tests (light-dark box and zero maze). The levels of adrenocorticotropic hormone and corticosterone, the most important markers of HPA axis, were also measured after behavioral tests. Our results indicated that mTBI-induced anxiety-related symptoms in mice through increased levels of adrenocorticotropic hormone and corticosterone, showing HPA axis hyperactivity. Interestingly, activation of CRF receptor by a subthreshold dose of CRF resulted in significant increases in anxiety-like behaviors and HPA axis response to stress, whereas blockade of CRF receptors by a subthreshold dose of antalarmin decreased anxiety-related symptoms and HPA axis response to stress in mTBI-induced mice. Collectively, these findings suggest that the CRF-1 receptor plays an important role in the regulation of anxiety-related behaviors following mTBI induction in mice and support the hypothesis that blockade of the CRF-1 receptor may be a promising therapeutic target for anxiety-related disorders in patients with TBI.
Asunto(s)
Ansiedad/metabolismo , Conmoción Encefálica/metabolismo , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Hormona Adrenocorticotrópica/análisis , Animales , Trastornos de Ansiedad/fisiopatología , Conmoción Encefálica/fisiopatología , Corticosterona/análisis , Hormona Liberadora de Corticotropina/metabolismo , Modelos Animales de Enfermedad , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Ratones , Ratones Endogámicos , Sistema Hipófiso-Suprarrenal/metabolismo , Pirimidinas/metabolismo , Pirroles/metabolismo , Receptores de Hormona Liberadora de Corticotropina/agonistas , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Estrés FisiológicoRESUMEN
Traumatic brain injury is a complex phenomenon leading to neurological diseases and persistent disability that currently affects millions of people worldwide. Increasing evidence shows that a wide range of patients with mild traumatic brain injury (mTBI) suffer from depression during the initial stages of injury and the post-acute stages of recovery. However, the underlying mechanisms involved in depression following mTBI are still not fully understood. The aim of this study was to determine whether serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor is involved in the regulation of depression-related behaviors following mild traumatic brain injury in mice. Mice with or without mTBI received intracerebroventricular injections of 5-HT1A receptor agonist (8-OH-DPAT) or antagonist (WAY-100635) for 5 days, then animals were subjected to behavioral tests. Four behavioral tests including novelty-suppressed feeding test, forced swim test, sucrose preference test and tail suspension test were used to evaluate depression-related symptoms in animals. Our results indicated that mTBI induction increased depression-like symptoms through altering serotonin 5-HT1A receptor activity in the brain. Activation of 5-HT1A receptor by a subthreshold dose of 8-OH-DPAT led to a significant decrease in depression-like behaviors, whereas blockade of 5-HT1A receptor by a subthreshold dose of WAY-100635 resulted in a considerable increase in depression-like phenotypes in mTBI-induced mice. The major strength of the present study is that depression-related symptoms were assessed in four behavioral tests. The present study supports the idea that disturbances in the function of serotonergic system in the brain following mTBI can play an important role in the regulation of depression-related behaviors.
Asunto(s)
Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Piperazinas/farmacología , Piridinas/farmacología , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Receptor de Serotonina 5-HT1A/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Conmoción Encefálica/tratamiento farmacológico , Conmoción Encefálica/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Masculino , RatonesRESUMEN
AIMS: There is increasing evidence showing that mild traumatic brain injury (mTBI) is associated with increased depression-related disorders in humans. Recent studies suggest that dietary intake or supplementation of natural flavonoids like hesperidin can be used for therapy of patients with brain injury and depression. However, the exact mechanisms by which hesperidin indicates its neuroprotective effects are not fully understood. The purpose of this study was to explore the influence of hesperidin on depression-related symptoms in a mouse model of mTBI, and that what mechanisms are primarily involved in the antidepressant effects of this bioflavonoid. MAIN METHODS: Ten days after mTBI-induction, mice received oral hesperidin treatment (50â¯mg/kg/14â¯days), then animals were subjected to different depression tests including sucrose preference test, forced swim test, novelty-suppressed feeding test, and tail suspension test. We also measured levels of tumor necrosis factor (TNF)-α, interleukin-(IL)-1ß, malondialdehyde (MDA), and brain-derived-neurotrophic-factor (BDNF) in the hippocampus. KEY FINDINGS: Our results show that mTBI induction induced depressive-like behaviors in mice by increasing inflammatory cytokines (IL-1ß and TNF-α) and oxidative stress marker (MDA), and reducing BDNF levels in the hippocampus. Interestingly, hesperidin treatment was effective to significantly reduce depression-related symptoms in mTBI-induced mice. In addition, hesperidin decreased the levels of IL-1ß, TNF-α and MDA, and increased BDNF levels in the hippocampus. The major strength of our study is that four behavioral tests gave similar results. SIGNIFICANCE: This study suggests that the antidepressant-like effect of hesperidin may be mediated, at least in part, by decreased neuroinflammation and oxidative damage, and enhanced BDNF production in the hippocampus.
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Depresión/tratamiento farmacológico , Hesperidina/farmacología , Animales , Antidepresivos/farmacología , Conmoción Encefálica/complicaciones , Conmoción Encefálica/tratamiento farmacológico , Citocinas/efectos de los fármacos , Trastorno Depresivo/tratamiento farmacológico , Modelos Animales de Enfermedad , Flavonoides/farmacología , Hipocampo/metabolismo , Inflamación/tratamiento farmacológico , Interleucina-1beta/efectos de los fármacos , Masculino , Malondialdehído/farmacología , Ratones , Factores de Crecimiento Nervioso/metabolismo , Fármacos Neuroprotectores/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacosRESUMEN
Early life overfeeding is associated with cognitive decline and anxiety-like behaviors in later life. It is not clear whether there are individual differences in the effects of early life overfeeding and what the underlying mechanistic pathways are. We investigated the long-lasting effects of small litter size, an experimental manipulation to induce neonatal overfeeding, in two strains of mice, C57BL/6 and NMRI. We measured body weight, learning and memory, anxiety-related behaviors, interleukin-(IL)-1ß and brain-derived-neurotrophic-factor (BDNF) levels in the hippocampus, and both basal and stress corticosterone levels in adult mice which have been nursed in small litters compared with those from control litters. Our findings showed that small litter size led to increased body weight in both strains of mice. Small litter size significantly decreased spatial memory and hippocampal BDNF levels, and increased hippocampal IL-1ß, in NMRI mice, but not C57BL/6 mice. Interestingly, we found that small litter size resulted in a significant increase in anxiety-like behaviors and stress-induced corticosterone in NMRI mice, whereas small litter size reduced anxiety-like symptoms and stress-induced corticosterone levels in C57BL/6 mice. These data show that small litter size, which is life-long associated with increased body weight, affects memory and anxiety-related behaviors in a strain-dependent manner in male mice. This suggests that there are individual differences in the developmental consequences of early life overfeeding.
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Ansiedad , Conducta Animal , Tamaño de la Camada , Memoria Espacial , Animales , Análisis Químico de la Sangre , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo/análisis , Corticosterona/sangre , Hipocampo/patología , Interleucina-1beta/análisis , Masculino , RatonesRESUMEN
Clinical and experimental studies have shown that mild traumatic brain injury (mTBI) is associated with increased anxiety- and depression-related behaviors and inflammation in the brain. Unfortunately, there are no specific therapies for long-term behavioral consequences of mTBI. This study set out to determine whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI induction in mice. We used open field, elevated plus maze, light-dark box, zero maze, sucrose preference, forced swim, and tail suspension tests to assess anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor necrosis factor (TNF)-α protein, a marker of inflammation, in the prefrontal cortex and hippocampus was also measured. This study identified that the long-term treatment with DZP, FLX or SIL results in decreased anxiety and depression-like behaviors in mTBI-induced mice. The results also showed that these drugs reduced TNF-α levels in the prefrontal cortex and hippocampus. In addition, there were no significant differences between the effects of SIL and DZP or SIL and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings support the idea that mTBI could be a risk factor for anxiety- and depression-related disorders and neuroinflammation in the brain. Taken together, this study demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and depression-like symptoms, and neuroinflammation after mTBI induction in mice.
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Ansiolíticos/farmacología , Antidepresivos/farmacología , Lesiones Traumáticas del Encéfalo/psicología , Diazepam/farmacología , Fluoxetina/farmacología , Silimarina/farmacología , Animales , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Cisplatin (Cis) has serious adverse side-effects that limit its clinical use. The mechanism underlying the effects is complex, including mitochondrial oxidative stress and inflammation. This study investigated whether Cornus mas, a fruit with high antioxidant contents, hydro-methanolic extract (CME) can modulate the cisplatin-induced changes. Forty Wistar rats were divided into a control group, Cis group, CME group, CME 300 + Cis group, and the CME 700 + Cis group. After the intervention, blood samples were taken for biochemical and hematological analysis. CME analysis showed noticeable total phenol and total antioxidant contents. The plasma glutathione peroxidase and catalase levels were significantly decreased and malondialdehyde and blood hemoglobin levels were significantly increased in the Cis group, which were reversed to the control levels in the CME + Cis groups. In the CME group, the red blood cell count was significantly lower and the red cell distribution width and hemoglobin distribution width levels were significantly higher. In the Cis-treated group, white blood cells, neutrophils, monocytes, basophils, and large unstained cells were significantly increased and lymphocytes were significantly decreased when compared with the control group that was reached to non-significant levels in CME 700 + Cis group. The blood cholesterol and high density lipoprotein in all CME-treated groups were significantly decreased. The eosinophils increased in the CME group significantly. The results showed considerable total antioxidant and total phenol contents and relative protective effects of CME against Cis-induced antioxidant and hematologic changes in rats.
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Objectives There is a significant prevalence of affective disorders including depression and anxiety in people with multiple sclerosis (MS), resulting in reduced quality of life. Since the current treatments are not generally effective, further studies are needed to find appropriate drugs to alleviate anxiety and depression symptoms in these patients. Methods The effects of a new analog of cyclomyrsinol diterpenes (TAMEC) isolated from Euphorbia sogdiana on the anxiety (open field and elevated plus maze test) and depressive-like behaviors (sucrose preference test and forced swim test) in EAE-induced C57BL/6 mice (EAE; a mouse model of MS) were investigated. Hippocampal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-10 levels were also measured by ELISA. Results The results indicated that TAMEC treatment reduced anxiety and depression-like behavior. This drug also decreased the levels of TNF-α and IL1ß and increased IL-10 level in the hippocampus. Discussion Taken together, our findings demonstrate that the drug we used here can reduce anxiety and depression-like symptoms in EAE-induced mice. However, more studies are still needed to validate, expand, and generalize these data.
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Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Diterpenos/farmacología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/psicología , Psicotrópicos/farmacología , Animales , Ansiedad/fisiopatología , Depresión/fisiopatología , Modelos Animales de Enfermedad , Diterpenos/química , Diterpenos/aislamiento & purificación , Encefalomielitis Autoinmune Experimental/fisiopatología , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Ratones Endogámicos C57BL , Estructura Molecular , Psicotrópicos/química , Psicotrópicos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic-pituitary-adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end, neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3-5, then dams during lactation (PND 6-20) and male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1ß) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1ß in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early life inflammation in adulthood.
Asunto(s)
Antibacterianos/farmacología , Hipocampo/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inflamación/tratamiento farmacológico , Minociclina/farmacología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Animales , Animales Recién Nacidos , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/inmunología , Trastornos de Ansiedad/prevención & control , Trastorno Depresivo/etiología , Trastorno Depresivo/inmunología , Trastorno Depresivo/prevención & control , Modelos Animales de Enfermedad , Femenino , Hipocampo/crecimiento & desarrollo , Hipocampo/inmunología , Sistema Hipotálamo-Hipofisario/crecimiento & desarrollo , Sistema Hipotálamo-Hipofisario/inmunología , Inflamación/fisiopatología , Lactancia , Lipopolisacáridos , Masculino , Ratones , Sistema Hipófiso-Suprarrenal/crecimiento & desarrollo , Sistema Hipófiso-Suprarrenal/inmunologíaRESUMEN
The use of plant extract in the biosynthesis of nanoparticles (NPs) can be an eco-friendly approach and have been suggested as a possible alternative to classic methods namely physical and chemical procedures. In this study, the biosynthesis of zinc oxide (ZnO) NPs by both "conventional heating" (CH) and "microwave irradiation" (MI) methods has been reported. Stable and spherical ZnONPs were produced using zinc nitrate and flesh extract of Rosa canina fruit (rosehip) which was used as a precursor. The flesh extract acts as a reducing and capping agent for generation of ZnONPs. The structural, morphological and colloidal properties of the as-synthesized NPs have been confirmed by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), Fourier transform Infrared (FT-IR) and Dynamic Light Scattering (DLS). In comparison with the CH method, the MI method has some advantages such as significantly short reaction time (within 8min) owing to the high heating rate and thus the accelerated reaction rate. Both methods led to the synthesis of nearly identical NPs with respect to shape and size according to the results of DLS, XRD and SEM techniques. The possible mechanism for synthesis pathway has been proposed based on FT IR results, XRD patterns, potentiometric data and antioxidant activity. In addition, the antibacterial activity of as-prepared ZnONPs was investigated against several bacteria such as Listeria monocytogenes, Escherichia coli, Salmonella typhimurium. Moreover, the efficacy of ZnONPs to treat cancer cell lines were measured by means of cell viability test via MTT assay in which concentrations of 0.05 and 0.1mg/mL of ZnONPs induced a very low toxicity. Thus, the present investigation reveals that ZnONPs have the potential for various medical and industrial applications.