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Recent advances in soft materials and mechanics activate development of many new types of electrical medical implants. Electronic implants that provide exceptional functions, however, usually require more electrical power, resulting in shorter period of usages although many approaches have been suggested to harvest electrical power in human bodies by resolving the issues related to power density, biocompatibility, tissue damage, and others. Here, we report an active photonic power transfer approach at the level of a full system to secure sustainable electrical power in human bodies. The active photonic power transfer system consists of a pair of the skin-attachable photon source patch and the photovoltaic device array integrated in a flexible medical implant. The skin-attachable patch actively emits photons that can penetrate through live tissues to be captured by the photovoltaic devices in a medical implant. The wireless power transfer system is very simple, e.g., active power transfer in direct current (DC) to DC without extra circuits, and can be used for implantable medical electronics regardless of weather, covering by clothes, in indoor or outdoor at day and night. We demonstrate feasibility of the approach by presenting thermal and mechanical compatibility with soft live tissues while generating enough electrical power in live bodies through in vivo animal experiments. We expect that the results enable long-term use of currently available implants in addition to accelerating emerging types of electrical implants that require higher power to provide diverse convenient diagnostic and therapeutic functions in human bodies.
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Corazón Auxiliar , Fotones , Dispositivos Electrónicos Vestibles , Tecnología Inalámbrica/instrumentación , Animales , Frecuencia Cardíaca , Ratones , Fenómenos Fisiológicos de la Piel , TransductoresRESUMEN
We measured the thermal conductivity of Araneus ventricosus' spider dragline silk using a suspended microdevice. The thermal conductivity of the silk fiber was approximately 0.4Wm-1K-1 at room temperature and gradually increased with an increasing temperature in a manner similar to that of other disordered crystals or proteins. In order to elucidate the effect of ß-sheet crystals in the silk, thermal denaturation was used to reduce the quantity of the ß-sheet crystals. A calculation with an effective medium approximation supported this measurement result showing that the thermal conductivity of ß-sheet crystals had an insignificant effect on the thermal conductivity of SDS. Additionally, the enhancement of bonding strength in a glycine-rich matrix by atomic layer deposition did not increase the thermal conductivity. Thus, this study suggests that the disordered part of the glycine-rich matrix prevented the peptide chains from being coaxially extended via the cross-linking covalent bonds.
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Glicina , Seda/química , Arañas/química , Conductividad Térmica , Animales , Cristalografía por Rayos X , Modelos Moleculares , Conformación Proteica en Lámina betaRESUMEN
Combining bioassays and analytical chemistry screening is a powerful approach to assess organic micropollutants which are the main contributors to toxic potential in complex mixtures of treated wastewater (TWW). The aim of this study was to perform a comprehensive toxicity assessment of treated effluents using stress response bioassays and then to assess the occurrence of the organic micropollutants which were responsible for this biological response using gas chromatography coupled with a mass spectrometry detector (GC/MS). Results showed that TWW samples induced significant stress response on Chinese hamster ovary cells, stably transfected with heat shock protein 47 promoter, at 0.1%, 1%, 5% and 10% concentrations. The organic chemical compounds responsible for stress response potential were identified at different percentage values using non-target chemical screening. Of the compounds detected in TWW1 and TWW4, 55.09% and 74.5% respectively, fell within the class of aliphatic hydrocarbons. Aliphatic hydrocarbons were also present in TWW3 at 26.46% whereas 11.96% corresponded to 6-acetyl-1,1,2,4,4,7-hexamethyltetralin and 16.08% to triethoxysilane. Moreover, 76.73% of TWW2 was recorded as decamethylcyclopentasiloxane (D5) and 17.44% as n-hexadecanoic acid.
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Proteínas del Choque Térmico HSP47/metabolismo , Compuestos Orgánicos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Bioensayo , Células CHO , Cricetinae , Cricetulus , Cromatografía de Gases y Espectrometría de Masas , Proteínas del Choque Térmico HSP47/genética , Compuestos Orgánicos/análisis , Aguas Residuales/análisis , Aguas Residuales/toxicidad , Contaminantes Químicos del Agua/análisisRESUMEN
The merging of high-throughput gene expression techniques, such as microarray, in the screening of natural products as anticancer agents, is considered the optimal solution for gaining a better understanding of the intervention mechanism. Red yeast rice (RYR), a Chinese dietary product, contains a mixture of hypocholesterolemia agents such as statins. Typically, statins have this effect via the inhibition of HMGCoA reductase, the key enzyme in the biosynthesis of cholesterol. Recently, statins have been shown to exhibit various beneficial antineoplastic properties through the disruption of tumor angiogenesis and metastatic processes. Mevinolin (MVN) is a member of statins and is abundantly present in RYR. Early experimental trials suggested that the mixed apoptotic/necrotic cell death pathway is activated in response to MVN exposure. In the current study, the cytotoxic profile of MVN was evaluated against MCF7, a breast cancerderived cell line. The obtained results indicated that MVNinduced cytotoxicity is multifactorial involving several regulatory pathways in the cytotoxic effects of MVN on breast cancer cell lines. In addition, MVNinduced transcript abundance profiles inferred from microarrays showed significant changes in some key cell processes. The changes were predicted to induce cell cycle arrest and reactive oxygen species generation but inhibit DNA repair and cell proliferation. This MVNmediated multifactorial stress triggered specific programmed cell death (apoptosis) and DNA degradation responses in breast cancer cells. Taken together, the observed MVNinduced effects underscore the potential of this ubiquitous natural compound as a selective anticancer activity, with broad safety margins and low cost compared to benchmarked traditional synthetic chemotherapeutic agents. Additionally, the data support further preclinical and clinical evaluations of MVN as a novel strategy to combat breast cancer and overcome drug resistance.
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Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Lovastatina/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Análisis de Secuencia de ARN/métodosRESUMEN
Linear alkylbenzene sulfonate (LAS) is a cytotoxic synthetic anionic surfactant widely present in the environment due to its large-scale production and intensive use in the detergency field. In this study, we investigated the effect of LAS (CAS No. 25155-30-0) at non cytotoxic concentrations on human intestinal Caco-2 cells using different in vitro bioassays. As results, LAS increased Caco-2 cell proliferation at concentrations ranging from 1 to 15 ppm, more significantly for shorter exposure time (24 h), confirmed using flow cytometry and trypan blue exclusion methods. Moreover, proteomics analysis revealed that this effect was associated with an over-expression of elongation factor 2 and dipeptidyl peptidase 3, and a down-regulation of 14-3-3 protein theta, confirmed at mRNA level using real-time PCR. These findings suggest that LAS at non cytotoxic concentrations, similar to those observed at wastewater treatment plants outlets, increases the growth rate of colon cancer cells, raising thereby its tumor promotion effect potential.
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The generation of blood cellular components from hematopoietic stem cells is important for the therapy of a broad spectrum of hematological disorders. In recent years, several lines of evidence suggested that certain nutrients, vitamins and flavonoids may have important roles in controlling the stem cell fate decision by maintaining their self-renewal or stimulating the lineage-specific differentiation. In this study, main olive leaf phytochemicals oleuropein (Olp), apigenin 7-glucoside (Api7G) and luteolin 7-glucoside (Lut7G) were investigated for their potential effects on hematopoietic stem cell differentiation using both phenotypic and molecular analysis. Oleuropein and the combination of the three compounds enhanced the differentiation of CD34+ cells into myelomonocytic cells and lymphocytes progenitors and inhibited the commitment to megakaryocytic and erythroid lineages. Treatment with Lut7G stimulated both the erythroid and the myeloid differentiation, while treatment with Api7G specifically induced the differentiation of CD34+ cells towards the erythroid lineage and inhibited the myeloid differentiation. Erythroid differentiation induced by Api7G and Lut7G treatments was confirmed by the increase in hemoglobin genes expressions (α-hemoglobin, ß-hemoglobin and γ-hemoglobin) and erythroid transcription factor GATA1 expression. As revealed by microarray analysis, the mechanisms underlying the erythroid differentiation-inducing effect of Api7G on hematopoietic stem cells involves the activation of JAK/STAT signaling pathway. These findings prove the differentiation-inducing effects of olive leaf compounds on hematopoietic stem cells and highlight their potential use in the ex vivo generation of blood cells.
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Apigenina/farmacología , Diferenciación Celular/efectos de los fármacos , Células Eritroides/citología , Eritropoyesis/efectos de los fármacos , Glucósidos/farmacología , Células Madre Hematopoyéticas/citología , Luteolina/farmacología , Olea/química , Línea Celular , Humanos , Fitoquímicos/farmacología , Hojas de la Planta/químicaRESUMEN
Black soybean is a health food has been reported to have antidiabetes effect. The onset of diabetes is closely associated with adipocyte differentiation, and at present, the effect of black soybean on adipocyte differentiation is unknown. Here, we investigated the antidiabetes effect of black soybean, and its anthocyanin cyanidin-3-glucoside (Cy3G), on adipocyte differentiation. Orally administered black soybean seed coat extract (BSSCE) reduced the body and white adipose tissue (WAT) weight of db/db mice accompanied by a decrease in the size of adipocytes in WAT. Furthermore, 3T3-Ll cells treated with BSSCE and Cy3G were observed to differentiate into smaller adipocytes which correlated with increased PPARγ and C/EBPα gene expressions, increased adiponectin secretion, decreased tumor necrosis factor-α secretion, activation of insulin signalling and increased glucose uptake. C2C12 myotubes cultured with conditioned medium, obtained from 3T3-L1 adipocyte cultures treated with Cy3G, also showed significantly increased expression of PGC-1α, SIRT1 and UCP-3 genes. Here we report that BSSCE, as well as its active compound Cy3G, has antidiabetes effects on db/db mice by promoting adipocyte differentiation. This notion is supported by BSSCE and Cy3G inducing the differentiation of 3T3-L1 preadipocytes into smaller, insulin-sensitive adipocytes, and it induced the activation of skeletal muscle metabolism. This is the first report on the modulation effect of Cy3G on adipocyte differentiation.
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Adipocitos/efectos de los fármacos , Antocianinas/farmacología , Diferenciación Celular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/farmacología , Glycine max/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipogénesis/efectos de los fármacos , Adiponectina/metabolismo , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Glicerolfosfato Deshidrogenasa/metabolismo , Hipoglucemiantes/farmacología , Insulina/metabolismo , Canales Iónicos/genética , Canales Iónicos/metabolismo , Masculino , Ratones , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Sirtuina 1/genética , Sirtuina 1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Desacopladora 3RESUMEN
Nitraria retusa is a halophyte species that is distributed in North Africa and used as a traditional medicinal plant. In this study, N. retusa ethanol extract and its constituent isorhamnetin (IRA) protected against amyloid ß (Aß)-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. An in vitro Aß aggregation assay suggested that IRA destabilizes Aß fibrils.
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Enfermedad de Alzheimer/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Agregación Patológica de Proteínas/tratamiento farmacológico , Quercetina/análogos & derivados , Enfermedad de Alzheimer/patología , Amiloide/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Humanos , Magnoliopsida/química , Extractos Vegetales/química , Agregación Patológica de Proteínas/patología , Quercetina/administración & dosificaciónRESUMEN
The medicinal plants can be used in the prevention or treatment of many diseases. Several studies concerning the potential of bioactive components in plants and food products and their link to obesity and related metabolic disorders, have been gaining big interest. Diabetes is a serious metabolic syndrome. Searching for alternative natural bioactive molecules is considered main strategy to manage diabetes through weight management. In the present study, an edible halophyte Nitraria retusa was selected and in vivo experiment was conducted using db/db model mice. We orally administrated its ethanol extract (NRE) to BKS.Cg-Dock7(m)+/+ Lepr(db/)J mice model for a period of 4 weeks. The effect was evaluated on the body weight and adiposity changes and on the biochemical parameters of db/db NRE-treated mice. The molecular mechanism underlying the anti-obesity effect was investigated by testing the gene expression related to hepatic lipid metabolism. NRE was found to significantly supress increases in body and fat mass weight, decreases triglycerides and LDL-cholesterol levels and enhances gene expression related to lipid homeostasis in liver showing anti-obesity actions. Our findings, indicate that NRE possesses potential anti-obesity effects in BKS.Cg-Dock7(m)+/+ Lepr(db/)J model mice and may relieve obesity-related symptoms including hyperlipidemia through modulating the lipolysis-lipogenesis balance.
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Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipólisis/efectos de los fármacos , Hígado/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Tracheophyta/química , Adiposidad/efectos de los fármacos , Administración Oral , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Etanol/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Obesidad/tratamiento farmacológico , Triglicéridos/sangreRESUMEN
The erythroid differentiation-inducing effect of apigenin and its derivatives on human chronic myeloid leukemia K562 has been reported but the functional group in its structure responsible for the effect has not yet been elucidated. Here, we determined the moiety responsible for the erythroid differentiation induction effect of apigenin by using different flavonoids to represent the functional groups in its structure. In addition, we compared apigenin and apigetrin, a flavonoid similar in structure to apigenin except for the glycoside in its structure. Morphological changes as well as expressions of specific markers in K562 cells treated with apigenin were compared with those treated with apigetrin, flavone, 7-hydroxyflavone, chrysin, luteolin, or naringenin. The anti-proliferative and erythroid differentiation-inducing effect of apigenin and the five flavonoids were then investigated and their effects on the α, ß, and γ globin genes expressions were compared using real-time PCR. Results of the comparison between apigenin and apigetrin revealed that the glycoside part of apigetrin does not have a role in the induction of cell differentiation. Based on glycophorin A expression, the potency of the other flavonoids for induction of differentiation, was: apigenin>chrysin>flavone/7-hydroxyflavone>luteolin/naringenin. Results of the analysis of the relationship between the structure and function of the flavonoids suggest that the apigenin-induced K562 cell differentiation was due to the 2-3 double bond and hydroxyl groups in its structure. This is the first study that identified the specific functional group in apigenin that impact the erythroid differentiation effect in K562 cells.
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Apigenina/farmacología , Diferenciación Celular/efectos de los fármacos , Células Eritroides/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Apigenina/química , Células Eritroides/citología , Humanos , Células K562 , Estructura Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Linear alkylbenzene sulfonate (LAS) is a synthetic anionic surfactant widely present in the environment due to its intensive production and use in the detergency field. Admitting that current procedure of risk assessment has limits in providing realistic risk assessment data and predicting the cumulative effect of the toxicant mixtures, the incorporation of information regarding the mode of action and cell response mechanism seems to be a potential solution to overcome these limits. In this regard, we investigated in this study the LAS cytotoxicity on human intestinal Caco-2 cells, trying to unveil the protein actors implicated in the cell response using proteomics approach in order to give a better understanding of the toxicological effect and allow the identification of appropriate biomarkers reflecting the mode of action associated with LAS. As results, we demonstrated that LAS induces a time- and dose-dependent cytotoxicity in Caco-2 cells accompanied by an induction of oxidative stress followed by an excessive increase of intracellular calcium level. Proteomics approach helped in discovering three informative biomarkers of effect associated with LAS cytotoxic effect, reported for the first time: calreticulin, thioredoxin, and heat shock cognate 71 (HSP7C), confirmed by real-time PCR and western blot analysis. These biomarkers could serve for more reliable future risk assessment studies that consider the toxicants mode of action in order to help in the prediction of potential cumulative effects of environmentally coexisting contaminants.
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Ácidos Alcanesulfónicos/toxicidad , Citotoxinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Tensoactivos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Biomarcadores/metabolismo , Western Blotting , Células CACO-2 , Calreticulina/metabolismo , Relación Dosis-Respuesta a Droga , Proteínas del Choque Térmico HSC70/metabolismo , Humanos , Proteómica/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Medición de Riesgo/métodos , Tiorredoxinas/metabolismoRESUMEN
Differentiation therapy is an attractive approach aiming at reversing malignancy and reactivating endogenous differentiation programs in cancer cells. Olive leaf extract, known for its antioxidant activity, has been demonstrated to induce apoptosis in several cancer cells. However, its differentiation inducing properties and the mechanisms involved are still poorly understood. In this study, we investigated the effect of Chemlali Olive Leaf Extract (COLE) for its potential differentiation inducing effect on multipotent leukemia K562 cells. Results showed that COLE inhibits K562 cells proliferation and arrests the cell cycle at G0/G1, and then at G2/M phase over treatment time. Further analysis revealed that COLE induces apoptosis and differentiation of K562 cells toward the monocyte lineage. Microarray analysis was conducted to investigate the underlying mechanism of COLE differentiation inducing effect. The differentially expressed genes such as IFI16, EGR1, NFYA, FOXP1, CXCL2, CXCL3, and CXCL8 confirmed the commitment of K562 cells to the monocyte/macrophage lineage. Thus our results provide evidence that, in addition to apoptosis, induction of differentiation is one of the possible therapeutic effects of olive leaf in cancer cells.
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Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Olea/química , Extractos Vegetales/farmacología , Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Monocitos/citología , Monocitos/efectos de los fármacos , Olea/metabolismo , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Transcriptoma/efectos de los fármacosRESUMEN
Heavy metal contamination of soil resulting from treated wastewater irrigation can cause serious concerns resulting from consuming contaminated crops. Therefore, it is crucial to assess hazard related to wastewater reuse. In the present investigation, we suggest the use of biomarker approach as a new tool for risk assessment of wastewater reuse in irrigation as an improvement to the conventional detection of physicochemical accumulation in irrigated sites. A field study was conducted at two major sites irrigated with treated wastewater and comparisons were made with a control site. Different soil depths were considered to investigate the extent of heavy metal leaching, the estrogenic activity, and the biomarker response. Results have shown that a longer irrigation period (20 years) caused a slight decrease in soil metal levels when compared to the soil irrigated for 12 years. The highest levels of Cr, Co, Ni, Pb, and Zn were detected at 20 and 40 cm horizons in plots irrigated with wastewater for 12 years. The latter finding could be attributed to chemical leaching to deeper plots for longer irrigation period. Furthermore, the treated wastewater sample showed a high estrogenic activity while none of the soil samples could induce any estrogenic activity. Regarding the stress response, it was observed that the highest stress shown by the HSP47 promoter transfected cells was induced by a longer irrigation period. Finally, the treated wastewater and the irrigated soils exhibited an overexpression of HSP60 in comparison with reference soil following 1 h exposure. In conclusion, in vitro techniques can be efficiently used to assess potential hazard related to wastewater reuse.
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Proteínas de Choque Térmico/metabolismo , Contaminantes del Suelo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Riego Agrícola , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisis , Túnez , Eliminación de Residuos Líquidos , Aguas Residuales/química , Contaminantes Químicos del Agua/análisisRESUMEN
Nitraria retusa is an edible halophyte, used in Tunisia for several traditional medicine purposes. The present study investigated the antiobesity effects of Nitraria retusa ethanol extract (NRE) in 3T3-L1 cells using different doses and in high-fat diet-induced obesity in mice. Male C57B6J/L mice were separately fed a normal diet (ND) or a high-fat diet (HFD) and daily administrated with NRE (50, 100 mg/kg) or one for 2 days with Naringenin (10 mg/kg). NRE administration significantly decreased body weight gain, fat pad weight, serum glucose, and lipid levels in HFD-induced obese mice. To elucidate the mechanism of action of NRE, the expression of genes involved in lipid and carbohydrate metabolism were measured in liver. Results showed that mice treated with NRE demonstrated a significant decrease in cumulative body weight and fat pad weight, a significant lowering in glucose and triglycerides serum levels, and an increase in the HDL-cholesterol serum level. Moreover mRNA expression results showed an enhancement of the expression of genes related to liver metabolism. Our findings suggest that NRE treatment had a protective or controlling effect against a high fat diet-induced obesity in C57B6J/L mice through the regulation of expression of genes involved in lipolysis and lipogenesis and thus the enhancement of the lipid metabolism in liver.
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This study aimed to determinate phenolic contents and antioxidant activities of the halophyte Arthrocnemum indicum shoot extracts. Moreover, the anticancer effect of this plant on human colon cancer cells and the likely underlying mechanisms were also investigated, and the major phenols were identified by LC-ESI-TOF-MS. Results showed that shoot extracts had an antiproliferative effect of about 55% as compared to the control and were characterised by substantial total polyphenol content (19 mg GAE/g DW) and high antioxidant activity (IC50 = 40 µ g/mL for DPPH test). DAPI staining revealed that these extracts decrease DNA synthesis and reduce the proliferation of Caco-2 cells which were stopped at the G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2) correlate with the changes in cell cycle distribution. Eight phenolic compounds were also identified. In conclusion, A. indicum showed interesting antioxidant capacities associated with a significant antiproliferative effect explained by a cell cycle blocking at the G2/M phase. Taken together, these data suggest that A. indicum could be a promising candidate species as a source of anticancer molecules.
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This study aimed to investigate the antistress properties of the ethanol extract of Cymbopogon schoenanthus (CSEE), growing wild in the southern part of Tunisia. The effect of extracts on H2O2-induced cytotoxicity and stress in human neuroblastoma SH-SY5Y cells. Its effect on stress-induced in ICR mice was exposed to force swim and tail suspension, in concordance with heat shock protein expression (HSP27 and HSP90), corticosterone, and catecholamine neurotransmitters level. Our results demonstrated that pretreatment of SH-SY5Y cells with CSEE at 1/2000, 1/1000, and 1/500 v/v dilutions significantly inversed H2O2-induced neurotoxicity. Moreover, CSEE treatments significantly reversed heat shock protein expression in heat-stressed HSP47-transformed cells (42°C, for 90 min) and mRNA expression of HSP27 and HSP90 in H2O2-treated SH-SY5Y. Daily oral administration of 100 mg/kg and 200 mg/kg CSEE was conducted to ICR mice for 2 weeks. It was resulted in a significant decrease of immobility time in forced swimming and tail suspension tests. The effect of CSEE on animal behavior was concordant with a significant regulation of blood serum corticosterone and cerebral cortex levels of catecholamine (dopamine, adrenaline, and noradrenaline). Therefore, this study was attempted to demonstrate the preventive potential of CSEE against stress disorders at in vitro and in vivo levels.
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Previous results demonstrated that capsaicin induces the reversible tight junctions (TJ) opening via cofilin activation. The present study investigated the mechanisms underlying the reversible TJ opening and compared the effect to the irreversible opening induced by actin inhibitors. Capsaicin treatment induced the F-actin alteration unique to capsaicin compared to actin-interacting agents such as latrunculin A, which opens TJ irreversibly. Along with TJ opening, capsaicin decreased the level of F-actin at bicellular junctions but increased it at tricellular junctions accompanied with its concentration on the apical side of the lateral membrane. No change in TJ protein localization was observed upon exposure to capsaicin, but the amount of occludin was decreased significantly. In addition, cosedimentation analyses suggested a decrease in the interactions forming TJ, thereby weakening TJ tightness. Introduction of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechanism, and suggest that it is a new type of paracellular permeability enhancer.
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Factores Despolimerizantes de la Actina/metabolismo , Actinas/metabolismo , Capsaicina/farmacología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Citoesqueleto/metabolismo , Ocludina/metabolismo , Uniones Estrechas/efectos de los fármacos , Animales , Línea Celular , Perros , Humanos , Células de Riñón Canino Madin Darby , Dominios y Motivos de Interacción de Proteínas , Transducción de Señal/efectos de los fármacos , Proteínas de Uniones Estrechas/metabolismo , Uniones Estrechas/metabolismoRESUMEN
6-Octadecynoic acid (6-ODA), a fatty acid with a triple bond, was identified in the methanol extract of Marrubium vulgare L. as an agonist of peroxisome proliferator-activated receptor γ (PPARγ). Fibrogenesis caused by hepatic stellate cells is inhibited by PPARγ whose ligands are clinically used for the treatment of diabetes. Plant extracts of Marrubium vulgare L., were screened for activity to inhibit fibrosis in the hepatic stellate cell line HSC-T6 using Oil Red-O staining, which detects lipids that typically accumulate in quiescent hepatic stellate cells. A methanol extract with activity to stimulate accumulation of lipids was obtained. This extract was found to have PPARγ agonist activity using a luciferase reporter assay. After purification using several chromatographic methods, 6-ODA, a fatty acid with a triple bond, was identified as a candidate of PPARγ agonist. Synthesized 6-ODA and its derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in different positions, activated PPARγ in a luciferase reporter assay and increased lipid accumulation in 3T3-L1 adipocytes in a PPARγ-dependent manner. There is little information about the biological activity of fatty acids with a triple bond, and to our knowledge, this is the first report that 6-ODA and 9-ODA function as PPARγ agonists.
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Ácidos Grasos Monoinsaturados/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , PPAR gamma/agonistas , Extractos Vegetales/farmacología , Células 3T3-L1 , Alquinos/farmacología , Animales , Ácidos Grasos Insaturados/farmacología , Humanos , Marrubium/química , RatonesRESUMEN
Argan (Argania spinosa L.) oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decrease in melanin content. Western blot results showed that the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) proteins were decreased. In addition, there was an increase in the activation of MITF and ERK1/2. Real-time PCR results revealed a downregulation of Tyr, Trp1, Dct, and Mitf mRNA expressions. Argan oil treatment causes MITF phosphorylation which subsequently inhibited the transcription of melanogenic enzymes, TYR and DCT. The inhibitory effect of argan oil on melanin biosynthesis may be attributed to tocopherols as well as the synergistic effect of its components. The results of this study provide the scientific basis for the traditionally established benefits of argan oil and present its therapeutic potential against hyperpigmentation disorders.
RESUMEN
Taking into account that oxidative stress is among the factors causing cancer-related death; chemoprevention which consists in using antioxidant substances such as phenolics could prevent cancer formation and progression. In the present study, phenolic contents and antioxidant activities of methanolic extracts from the halophyte Tamarix gallica shoots were determined. Moreover, the anticancer effect of this species on human colon cancer cells and the likely underlying mechanisms were also investigated. Shoot extracts showed an appreciable total phenolic content (85 mg GAE/g DW) and a high antioxidant activity (IC50 = 3.3 µg/ml for DPPH test). At 50 and 100 µg/ml, shoot, leaf, and flower extracts significantly inhibited Caco-2 cell growth. For instance, almost all plant part extracts inhibited cell growth by 62 % at the concentration 100 µg/ml. DAPI staining results revealed that these extracts decrease DNA synthesis and confirm their effect on Caco-2 cells proliferation, principally at 100 µg/ml. More importantly, cell mitosis was arrested at G2/M phase. The changes in the cell-cycle-associated proteins (cyclin B1, p38, Erk1/2, Chk1, and Chk2) are correlated with the changes in cell cycle distribution. Taken together, our data suggest that T. gallica is a promising candidate species to be used as a source of anticancer biomolecules.