RESUMEN
Sonchus oleraceus (L.) L. (Asteraceae) is an edible wild plant, known for its uses in traditional medicine. The aim of this study is to explore the phytochemical composition of the aerial parts (AP) and roots (R) of aqueous extracts of Sonchus oleraceus L. growing in Tunisia, using liquid chromatography-tandem mass spectrometry(LC/MS/MS), and determine the content of polyphenols and antioxidant activities. Results showed that aqueous extracts of AP and R contained, respectively, 195.25±33â µg/g and 118.66±14â µg/g gallic acid equivalent (GAE), and 52.58±7â µg/g and 3.2±0.3µg/g quercetin equivalent. AP and R extracts also contained tannins, 581.78±33â µg/g and 948.44±19â µg/g GAE. The AP extract in the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activities, hydroxyl radical scavenging (OH-) and in cupric reducing antioxidant activity (CUPRAC) assays were respectively 0.325±0.036â mg/mL, 0.053±0.018â mg/mL, 0.696±0.031â mg/mL and 60.94±0.004â µMTE/g, while the R extract using the same assays showed, 0.209±0.052â mg/mL, 0.034±0.002â mg/mL, 0.444±0.014â mg/mL and 50.63±0.006â µM Trolox equivalent/g, respectively. A total of 68â compounds were tentatively identified by LC/MS/MS in both extracts in which quinic acid, pyrogallol, osthrutin, piperine, gentisic acid, fisetin, luteolin, caffeic acid, gingerol, were the most abundant in the LC/MS/MS spectrum. Many of these metabolites were found for the first time in Tunisian Sonchus oleraceus L. which may take account for the antioxidant activities exhibited by the plant.
Asunto(s)
Antioxidantes , Sonchus , Antioxidantes/farmacología , Antioxidantes/química , Espectrometría de Masas en Tándem/métodos , Extractos Vegetales/química , Polifenoles/química , Ácido Gálico , Flavonoides/químicaRESUMEN
Cancer is a class of diseases characterized by uncontrolled cell growth. One of the main aims of developing new therapies is to use natural resources to induce apoptosis. LC-ms/ms analysis of a methanolic extract of Ephedra alata (E.A.) allowed the identification of 20 secondary metabolites, including flavonoids, phenolic acids, and proanthocyanidins. Antiproliferative effect was assessed by crystal violet assay. Antimigration effect was tested by wound healing assay and apoptosis induction was determined by annexin binding assays, Hoechst staining, ROS production, and activation of apoptotic proteins. The results indicated that exposure of breast cancer cells to E.A. extract significantly reduced cell viability in a dose and time-dependent manner and inhibited the migration of 4T1 cells at a low dose. Moreover, treatment of cells with E.A. extract induced apoptosis, as it was detected by Annexin V/7 AAD, Hoechst staining, ROS production, and the activation of caspases.Abbreviation:BSAbovine serum albuminDMSOdimethyl sulfoxideEDTAethylenediaminetetraacetic acidLC-ms/msliquid chromatography-mass spectrometryNACN-acetyl-l-cysteinePARPpoly(ADP-ribose) polymerasePMSFphenylmethylsulfonyl fluorideRIPAradioimmunoprecipitation assay bufferROSreactive oxygen speciesRPMIRoswell park memorial instituteSDS-PAGEsodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Asunto(s)
Neoplasias de la Mama , Ephedra , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Cromatografía Liquida , Ephedra/química , Ephedra/metabolismo , Femenino , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Espectrometría de Masas en TándemRESUMEN
Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases.
Asunto(s)
Flavonas , Melanoma Experimental , Melanoma , Rhamnus , Animales , Línea Celular Tumoral , Proliferación Celular , Citocinas , Flavonas/farmacología , Flavonoides/farmacología , Humanos , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Extractos Vegetales/farmacologíaRESUMEN
Tissue engineering involves the use of smart biomimetic hybrid matrices to reinforce the cellular interaction with the matrix and restore native properties after regeneration. In this study, we highlight the potential of 3D collagen sponges soaked with bioactive extract, to enhance the wound healing process in vivo. Acid-soluble collagen from two sources, marine and bovine, were extracted and characterized physiochemically using Fourier transform infrared spectroscopy (FTIR) and SDS-PAGE. Our results confirmed that the extracted collagens were mainly composed of collagen type I with slight molecular structure differences. Both collagens present two different α chains (α1 and α2) and one ß chain. Highly interconnected 3D scaffolds from collagen from the skin are designed and added by the widely known healing plants Pistacia lentiscus and Calendula officinalis. The resulting 3D collagen matrices possess fine biocompatibility with skin cells, Hacat (keratinocytes), and 3T3-L1 (fibroblasts) cells. To evaluate the potential wound healing effect, a collagen sponge soaked with the bioactive extract was tested on BALB/c mice. Our findings confirmed that sponges significantly improve animal re-epithelialization by increasing wound closure. Consequently, spongy collagen scaffolds loaded with Pistacia lentiscus and Calendula officinalis could be used as potential wound dressing material.
Asunto(s)
Colágeno , Extractos Vegetales , Animales , Bovinos , Colágeno/química , Colágeno/farmacología , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Piel , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Cicatrización de HeridasRESUMEN
Water pollution is one of the major challenges and is of serious concern in the world. Toxicities generated by industrial activities severely deteriorate aquatic and terrestrial ecosystems during their uncontrolled discharge and accentuate water scarcity problems. An adequate treatment of released effluents seems to be mandatory. This study investigated the effect of synthetic textile wastewater (STWW) before and after an innovative algal-bacterial treatment occurred under anoxic-aerobic conditions on growth and mineral contents of radish plants. The health risk assessment was performed after the consumption of irrigated plants by rats. Results revealed a significant reduction in heavy metals content in plants irrigated with treated STWW, and rats fed with these plants showed normal health status. Rats fed with plants irrigated with raw STWW showed a disturbance of their homeostasis. The innovative treatment using algal-bacteria under anoxic-aerobic conditions succeeds to reduce the toxicity of raw STWW and provide an alternative water resource able to tackle water shortage.
Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Ratas , Animales , Aguas Residuales/análisis , Fotobiorreactores , Ecosistema , Textiles , Metales Pesados/toxicidad , Metales Pesados/análisis , Bacterias/genética , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos/métodosRESUMEN
Anticancer drugs, such as Mitomycin C (MMC), can interact with biological molecules and cause genetic damage in normal cells. In this respect, we investigated the potential of chrysin, a flavone known as a potent scavenger of free radicals generated by anticancer agents, to protect mice against MMC-induced genotoxicity. The amount of DNA damage in the liver, kidney and bone marrow cells, in Balb/C mice treated with MMC (6 mg/kg, i.p) and the frequency of chromosomal aberrations indicated the genotoxic effect of MMC. Besides, a significant increase in the activities of antioxidant enzymes (SOD, CAT, GPx, GST) and lipid peroxidation is revealed. On the other hand, we noticed a regression of the genotoxic effect when studying the same parameters in Balb/C mice treated with chrysin (40 mg/kg b. wt., i.p) 24 h prior to MMC (6 mg/kg, i.p) injection. This study concluded that the protective effect of chrysin against genotoxicity of MMC results partly from its antioxidant effect.
Asunto(s)
Flavonas , Mitomicina , Animales , Daño del ADN , Flavonoides , Ratones , Ratones Endogámicos BALB C , Mitomicina/toxicidad , Estrés OxidativoRESUMEN
In recent years, there has been a growing interest in the screening of natural active ingredients from Eucalyptus essential oils because of their evident importance in practical utility and their undeniable therapeutic properties. Based on this, the aim of the present study was to investigate the chemical profile of the essential oils of the trunk bark of Eucalyptus torquata Luehm. (ETEO), and E.â salmonophloia F.â Muell. (ESEO), growing in Tunisia. The inâ vitro cytotoxic properties of the extracted EOs were also evaluated against two human cancer cell lines: breast carcinoma cell lines MDA-MB-231 and colorectal cancer cell lines SW620. The analysis by gas chromatography coupled with mass spectrometry (GC/MS) led to the identification of 32 compounds from the ETEO, with the dominant constituents being the monoterpenes trans-myrtanol (73.4 %) and myrtenol (4.7 %), and the apocarotene (E)-ß-ionone (3.9 %). In the case of ESEO, 29 compounds were identified with trans-myrtanol (25.0 %), decanoic acid (22.1 %), nonanoic acid (9.8 %), γ-elemene (6.5 %), γ-maaliene (5.5 %), and α-terpineol (5.3 %) as the main components. The cytotoxicity of EOs against the two chosen cell lines was tested using Crystal Violet Staining (CVS) assay and 5-fluorouracil as a reference drug. The two EOs exhibited a significant dose-dependent inhibition against the viability of the used cell lines. Their inhibitory effects were particularly observed towards SW620 colon carcinoma cells with IC50 values of 26.71±1.22 and 22.21±0.85â µg/mL, respectively, indicating that both oils were more cytotoxic for SW620 cells compared to MDA-MB-231 one.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Eucalyptus/química , Aceites Volátiles/farmacología , Componentes Aéreos de las Plantas/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificaciónRESUMEN
The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4-70.2%) were detected, mainly consisting of caryophyllene oxide (13.1-26.6%), carotol (9.2-21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2-15.5%) and humulene epoxide II (2.6-7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 µg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 µg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata.
Asunto(s)
Cupressaceae/química , Cupressaceae/crecimiento & desarrollo , Aceites Volátiles/química , Aceites Volátiles/farmacología , Corteza de la Planta/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fraccionamiento Químico , Humanos , Concentración 50 Inhibidora , TúnezRESUMEN
Coxsackie B viruses (CV-B) are usually transmitted via the fecal-oral route and the virus gains the central nervous system (CNS) via the bloodstream. Nevertheless, other routes of spread of the virus to the CNS cannot be excluded, including the neuronal route. Neuronal cells, as well as non-neuronal cells (fibroblasts), were isolated from mice and inoculated with CV-B4 in the absence and presence of neutralizing serum. In the absence of neutralizing serum, virus titers recorded in neuron cultures and rates of infected neurons were non-significantly different compared to those recorded in fibroblast cultures. Higher cell mortality was noted among neurons than fibroblasts. The addition of neutralizing serum to neurons did not reduce significantly virus titers or rates of infected cells and cell viability was not significantly augmented, while virus titers and rates of infected fibroblasts were significantly reduced and their viability was significantly enhanced as well. Our results demonstrate the ineffectiveness of neutralizing serum to prevent neurons infection with CV-B4 which suggests a trans-synaptic transmission of CV-B4 between neurons.
Asunto(s)
Infecciones por Coxsackievirus , Animales , Sistema Nervioso Central , Enterovirus Humano B , Ratones , Neuronas , Carga ViralRESUMEN
Aim: A large number of plant-derived products have been approved for the treatment of numerous types of cancer, and these products have also shown to reduce the effects of metastatic cancer. The aim of this study is to evaluate the anticancer effects of a methanolic extract of Bryonia dioïca root (M extract) against B16F10 melanoma cancer cells in vitro as well as in vivo.Results: It was shown to induce apoptosis, in vitro, and to inhibit cell growth by arresting cell cycle progression in SubG1 phase. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the M extract as an antitumor promoting agent. In mice dosed with 50 mg M/kg/d (for 28 days), tumor weight was inhibited by 65.03% compared to that in mice that did not receive the product. Our results demonstrate on the one hand, that this inhibition was accompanied by a drastic decrease regulation of complex FAK, Src, ERK, p130Cas and paxillin. On the other hand, it was marked by a measurable decrease of the metastatic descent in the lungs.Conclusions: These effects could be ascribed to the presence of bryoniosides and cucurbitacins such as cucurbitacin A and cucurbitacin G in M extract.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Bryonia/química , Melanoma Experimental/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Técnicas In Vitro , Masculino , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Carga Tumoral/efectos de los fármacosRESUMEN
Colorectal cancer is a malignancy with a high incidence. Currently, the drugs used in chemotherapy are often accompanied by strong side effects. Natural secondary metabolites can interfere with chemotherapeutic drugs and intensify their cytotoxic effects. This study aimed to profile the secondary metabolites from the methanol extract of Scabiosa atropurpurea and investigate their in vitro activities, alone or in combination with the chemotherapeutic agent doxorubicin. MTT assay was used to determine the cytotoxic activities. Annexin-V/PI double-staining analysis was employed to evaluate the apoptotic concentration. Multicaspase assay, quantitative reverse transcription real-time PCR (RT-qPCR), and ABC transporter activities were also performed. LC-MS analysis revealed 31 compounds including phenolic acids, flavonoids, and saponins. S. atropurpurea extract intensified doxorubicin anti-proliferative effects against resistant tumor cells and enhanced the cytotoxic effects towards Caco-2 cells after 48 h. The mRNA expression levels of Bax, caspase-3, and p21 were increased significantly whereas Bcl-2 expression level was decreased. Furthermore, the methanol extract reversed P-glycoprotein or multidrug resistance-associated protein in Caco-2 cells. In conclusion, S. atropurpurea improved chemosensitivity and modulated multidrug resistance in Caco-2 cells which makes it a good candidate for further research in order to develop a new potential cancer treatment.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Colorrectales/patología , Dipsacaceae/química , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Extractos Vegetales/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis , Células CACO-2 , Caspasas/metabolismo , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Combinación de Medicamentos , Resistencia a Múltiples Medicamentos , Humanos , Concentración 50 Inhibidora , Metanol/química , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Hojas de la Planta/química , Polifenoles/químicaRESUMEN
Hyperlipidemia is a serious health threat that has been linked to oxidative stress and systemic inflammation, causing among many other disorders essentially liver disease. The current study was conducted to evaluate the antihyperlipidemic, antioxidant and anti-inflammatory potential of methanol leaf extract from Erica multiflora (M-EML). Triton WR-1339-induced hyperlipidemic rats were divided into six groups: control group (CG), hyperlipidemic group (300â¯mg/kg body weight "BW") (HG), hyperlipidemic group treated with M-EML (150 and 250â¯mg/kg) (HG + M-EML), normal rats treated with M-EML (250â¯mg/kg) and fenofibrate-treated group (HG + FF) (65â¯mg/kg). After 24â¯h of administration, triton WR-1339 induced a significant increase in lipid profile, atherogenic index (AI) and Coronary Risk Index (CRI) in HG group compared to control group. Furthermore, triton WR-1339 administration induced alteration in the status of pro-inflammatory markers (aspartate transaminase, alanine transaminase, IFN-γ and Nitric oxide production). HG group showed also, a high level of lipid peroxidation, an altered antioxidant enzyme profiles and an increase in DNA damages, in liver. However, orally administration of M-EML mitigates significantly these disorders, proving hence a protective potential against triton WR-1339-induced hyperlipidemia. These findings suggest that M-EML extract could be used as functional foods and natural adjuvant treatment of hyperlipidemia.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Ericaceae , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/química , Antioxidantes/química , Fenofibrato/uso terapéutico , Hiperlipidemias/inducido químicamente , Hipolipemiantes/química , Hígado/efectos de los fármacos , Masculino , Fitoquímicos/análisis , Fitoquímicos/uso terapéutico , Extractos Vegetales/química , Hojas de la Planta , Polietilenglicoles , Ratas WistarRESUMEN
This study evaluated the antitumoral effect of Chloroform extract from Nitraria retusa leaves, via its major compounds ß-sitosterols and palmitic acid. BALB/c mice were subcutaneously inoculated with B16-F10 cells, then treated intra-peritoneally after 7 days with the chloroform extract for 21 days. They were then euthanized, and the tumors were weighed. Lung parenchyma was analyzed. Lymphocyte and macrophages proliferation, cytotoxic T lymphocyte (CTL) activities were evaluated using the MTT assay. Macrophage phagocytosis was evaluated by measuring the lysosomal activity and nitric oxide production. Antioxidant activity was studied by cellular antioxidant activity on macrophage and splenocytes and by lipid peroxidation inhibitory activity in liver cells, kidney, and serum. ß-sitosterols and palmitic acid, major compounds of chloroform extract, impeded remarkably the expansion of the transplantable tumor, protected the lung parenchyma, and increased splenocytes proliferation and both CTL activities in tumor-bearing mice. ß-sitosterols and palmitic acid were also seen to have enhanced lysosomal activity of host macrophages and antioxidant cellular activity. Also, they showed an inhibitory effect of lipid peroxidation. Our results suggest that antitumoral effect of ß-sitosterols and palmitic acid from chloroform extract is related with its immunomodulatory activity, and opens the way for a nutrition application and coprocessing phytotherapy against cancer.
Asunto(s)
Factores Inmunológicos/farmacología , Magnoliopsida/química , Ácido Palmítico/farmacología , Extractos Vegetales/farmacología , Sitoesteroles/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cloroformo/química , Peroxidación de Lípido/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Extractos Vegetales/análisis , Extractos Vegetales/química , Hojas de la Planta/química , Plantas Medicinales/química , Túnez , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The pervasive of bacterial resistance earnestly threaten the prevention and the treatment of infectious diseases. Therefore, scientific communities take precedence over development of new antimicrobial agents. The aim of the study was to determine antimicrobial potency of three North-African essential oils Pituranthos chloranthus, Teucruim ramosissimum and Pistacia lentiscus individually, and in combination with antibiotics, to inhibit the growth of highly resistant clinical pathogen. Bacteria clinically isolated from patients, subsequently, challenged to a panel of drugs to determine the antibiotic-resistance profiles. Drugs displaying clinically irrelevant CMI were subjected to further studies in order to rescue antibiotic actions. Singular activity of essential oils and activity when combined with an antibiotic was hence elucidated. The results obtained highlighted the occurrence of strong antibacterial potential of essential oils when administrated alone. In the interactive experiment essential oils were found highly effective in reducing the resistance of Methicillin-resistant Staphylococcus aureus to amoxicillin, tetracycline, piperacillin, ofloxacin and oxacillin and resistance of Acinetobacter baumannii to amoxicillin and to ofloxacin in interactive manner. Furthermore, the results proved synergism among essential oils and both antibiotics ofloxacin and novobiocin against the Extended-Spectrum Beta-Lactamase producing E. coli (ESBL). Time kill kinetics was performed with a combination of sub-inhibitory concentrations to confirm the efficiency and killing rate of the combination over time. Further, the hypothetical toxicity of essential oils against human keratinocytes HaCat and murine spleenocytes were examined. The chemical composition of essential oils was assessed by GC/MS analysis and the major constituents found were sabinene, limonene, terpinen-4-ol, and ß-eudesmol.
Asunto(s)
Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Acinetobacter baumannii/efectos de los fármacos , Amoxicilina/farmacología , Animales , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Monoterpenos Bicíclicos , Línea Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Ciclohexenos/química , Combinación de Medicamentos , Sinergismo Farmacológico , Escherichia coli/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Queratinocitos/efectos de los fármacos , Limoneno , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana/métodos , Monoterpenos/química , Novobiocina/farmacología , Ofloxacino/farmacología , Aceites Volátiles/química , Oxacilina/farmacología , Piperacilina/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Aceites de Plantas/química , Sesquiterpenos de Eudesmano/química , Bazo/efectos de los fármacos , Terpenos/química , Tetraciclina/farmacología , Factores de Tiempo , beta-Lactamasas/efectos de los fármacosRESUMEN
Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses and to reduce damage to the human body. To determine whether phenolic compounds (caffeic, ferulic, and p-coumaric acids) have immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we evaluated their effect on splenocyte proliferation and lysosomal enzyme activity. We also investigated the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In addition, induction of the cellular antioxidant activity in splenocytes, macrophages, and red blood cells was determined by measuring the ï¬uorescence of the DCF product. The study first results indicated that caï¬eic, ferulic, and p-coumaric acids significantly promote LPS-stimulated splenocyte proliferation, suggesting a potential activation of B cells, and enhanced humoral immune response in hosts treated by the tested natural products. Phenolic acids significantly enhanced the killing activity of isolated NK and CTL cells but had negligible effects on mitogen-induced proliferation of splenic T cells. We showed that caffeic acid enhances lysosomal enzyme activity in murine peritoneal macrophages, suggesting a potential role in activating such cells. Immunomodulatory activity was concomitant with the cellular antioxidant effect in macrophages and splenocytes of caffeic and ferulic acids. We conclude from this study that caï¬eic, ferulic, and p-coumaric acids exhibited an immunomodulatory effect which could be ascribed, in part, to their cytoprotective effect via their antioxidant capacity. Furthermore, these results suggest that these natural products could be potentially used to modulate immune cell functions in physiological and pathological conditions.
Asunto(s)
Antioxidantes/metabolismo , Ácidos Cafeicos/metabolismo , Ácidos Cumáricos/metabolismo , Factores Inmunológicos/metabolismo , Células Asesinas Naturales/metabolismo , Propionatos/metabolismo , Linfocitos T Citotóxicos/metabolismo , Animales , Antioxidantes/efectos adversos , Antioxidantes/química , Ácidos Cafeicos/efectos adversos , Ácidos Cafeicos/química , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ácidos Cumáricos/efectos adversos , Ácidos Cumáricos/química , Suplementos Dietéticos/efectos adversos , Inmunidad Celular , Factores Inmunológicos/efectos adversos , Factores Inmunológicos/química , Células Asesinas Naturales/citología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Activación de Linfocitos/efectos de los fármacos , Macrófagos Peritoneales/citología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Masculino , Ratones Endogámicos BALB C , Mitógenos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Propionatos/efectos adversos , Propionatos/química , Bazo/citología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismo , Relación Estructura-Actividad , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC.
Asunto(s)
Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Crataegus/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Acetatos/química , Antineoplásicos/farmacología , Western Blotting , Caspasa 8/metabolismo , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Fragmentación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HCT116 , Células HT29 , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Fluorescente , Poli(ADP-Ribosa) Polimerasa-1/metabolismoRESUMEN
A large number of plants used in traditional medicines have been shown to possess antitumor activities. The aims of this study were to evaluate any anticancer effect of the essential oil (EO) extracted from P. tortuosus against B16F10 melanoma cancer cells in vitro as well as in vivo. In vitro, EO was shown to induce apoptosis and to inhibit migration and invasion processes. Further investigation revealed that EO decreased focal adhesion and invadopodia formation which was accompanied by a drastic downregulation of FAK, Src, ERK, p130Cas and paxillin. Moreover, EO treatment decreased the expression level of p190RhoGAP, and Grb2, which impair cell migration and actin assembly. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the EO as an anti-tumor promoting agent. In mice dosed with 100 mg EO/kg/d (for 27 days), tumor weight was inhibited by 98% compared to that in mice that did not receive the product. In conclusion, these data suggested to us that an EO of P. tortuosus could evolve to be a potential medicinal resource for use in the treatment of cancers.
Asunto(s)
Apiaceae/química , Proteína-Tirosina Quinasas de Adhesión Focal/antagonistas & inhibidores , Melanoma Experimental/tratamiento farmacológico , Aceites Volátiles/farmacología , Proteínas Proto-Oncogénicas pp60(c-src)/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Adhesiones Focales/efectos de los fármacos , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones Endogámicos BALB C , Invasividad Neoplásica , Fitoterapia , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Carga Tumoral/efectos de los fármacosRESUMEN
Evaluation of the immunomodulatory activity of plant compounds is an interesting and growing area of research. Teucrium ramosissimum Desf. is a native and endemic medicinal plant from the South of Tunisia traditionally used for the treatment of many diseases. The anti-inflammatory activity of apigenin-7-glucoside, genkwanin, and naringenin isolated from T. ramosissimum were assayed. The phagocytic activities of macrophage and lymphocyte proliferation were investigated in the absence and presence of mitogens (lipopolysaccharide [LPS] or lectin). Depending on the concentrations, the compounds affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide (NO) release. The tested compounds enhance significantly splenocyte proliferation, either with or without mitogen stimulation. In studies to assess any potential effects of apigenin-7-glucoside, genkwanin, and naringenin on innate immunity, the results showed that these compounds significantly enhanced the killing activity of natural killer (NK) cells and cytotoxic activity of the T lymphocyte (CTL) isolated from splenocytes. These results suggest that T. ramosissimum compounds such as apigenin-7-glucoside, genkwanin, and naringenin may be potentially useful for modulating immune cell functions in physiological and pathological conditions.
Asunto(s)
Antioxidantes/farmacología , Inmunidad Innata/efectos de los fármacos , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Linfocitos T Citotóxicos/efectos de los fármacos , Teucrium/química , Animales , Antioxidantes/aislamiento & purificación , Apigenina/aislamiento & purificación , Apigenina/farmacología , Células Cultivadas/efectos de los fármacos , Endotoxinas/farmacología , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Flavonas/aislamiento & purificación , Flavonas/farmacología , Factores Inmunológicos/aislamiento & purificación , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/enzimología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Plantas Medicinales/química , Mitógenos de Phytolacca americana/farmacología , Proteínas Inactivadoras de Ribosomas/farmacología , Organismos Libres de Patógenos Específicos , Linfocitos T Citotóxicos/inmunología , TúnezRESUMEN
Cancer metastasis is the major cause of cancer-related death. Chemoprevention is defined as the use of natural or synthetic substances to prevent cancer formation or cancer progress. In the present study, we investigate the antitumor activity of esculin and its oligomer fractions in U87 glioblastoma cells. We showed that esculin and its oligomers reduced U87 cell growth in a dose dependent manner. They also inhibited cell adhesion to collagen IV and vitronectin by interfering with the function of their respective receptors α2ß1 and αvß5 integrins. Furthermore, the tested samples were able to reduce migration of U87 cells towards another extracellular matrix fibronectin. Moreover, esculin and its oligomer fractions inhibited in vitro angiogenesis of endothelial cells (HMEC-1). In summary, our data provide the first evidence that esculin and its oligomer fractions are able to reduce adhesion, migration of glioblastoma cells and in vitro angiogenesis. Esculin and its oligomers may thus exert multi-target functions against cancer cells.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Esculina/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dimerización , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Esculina/química , Glioblastoma/irrigación sanguínea , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Integrina alfa2beta1/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Patológica/prevención & control , Receptores de Vitronectina/metabolismoRESUMEN
Laccase was used to enzymatically polymerize esculin. Oligoesculin fraction was obtained after ultrafiltration through a 5-kDa membrane. Several studies have been carried out to prove the effectiveness of natural substances such as immunomodulators to promote the anti-cancer activity in situ. The purpose of our report was to explore whether the anti-tumor potential of the oligoesculin fraction in vitro and in vivo is linked to its immunological mechanisms in melanoma-bearing mice. We revealed that oligoesculin fraction reduced B16-F10 proliferation and migration in vitro in a dose-related manner. Moreover, melanin synthesis and tyrosinase activity were inhibited in these melanoma cells in a concentration-dependent way. The anti-tumor potential of oligoesculin fraction was also assessed in vivo. Our results showed that intraperitoneal administration of oligoesculin fraction, at 50 mg/kg body weight (b.w.) for 21 days, reduced tumor size and weight with percentages of inhibition of 94 and 87 %, respectively. Oligoesculin fraction was effective in promoting lysosomal activity and nitric oxide (NO) production by peritoneal macrophages in tumor-implanted mice. In addition, the activities of natural killer (NK), cytotoxic T lymphocytes, and macrophages were significantly enhanced by oligoesculin fraction. These findings suggested that this polymer with its anti-tumor and immunomodulatory properties could be used for the treatment of melanoma.