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1.
Environ Sci Pollut Res Int ; 27(11): 12792-12801, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32008195

RESUMEN

Cisplatin (CP) is a powerful anticancer agent used in the treatment of a diverse type of cancers. Oxidative stress is one of the most important side effects limiting the use of cisplatin. The protective effects of methanolic extract (ME) and ephedrine (EP), major compound, of Ephedra alata on CP-induced damages were here assessed. Treatment with CP-induced nephrotoxicity and hepatotoxicity characterized by biochemical alterations. In fact, using CP reduced significantly glutathione (GSH) levels, enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and increased malondialdehyde (MDA) content. Nonetheless, CP-treatment induced DNA damage at renal, hepatic, and blood cells and increased interferon gamma (IFNγ) level in serum. Co-treatments of mice with ME normalized relative kidney/body weight, restored biochemical and oxidative stress parameters, reduced DNA damage and IFNγ level. In conclusion, ME exhibited the best protective effect against CP damage compared with ephedrine. This is could be attributed to the presence of polysaccharides, organic acids, flavonoids, and tannins in addition to ephedrine alkaloids. These compounds were reported to play a major role in inhibiting and scavenging free radicals, providing an effective protection against CP- induced oxidative damage. Graphical abstract.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Ephedra , Animales , Antioxidantes , Cisplatino , Daño del ADN , Glutatión , Riñón , Metanol , Ratones , Estrés Oxidativo , Extractos Vegetales
2.
Regul Toxicol Pharmacol ; 107: 104404, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31199997

RESUMEN

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 (300 mg/kg body weight "BW") (HG), hyperlipidemic group treated with M-EML (150 and 250 mg/kg) (HG + M-EML), normal rats treated with M-EML (250 mg/kg) and fenofibrate-treated group (HG + FF) (65 mg/kg). After 24 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 Wistar
3.
Chemosphere ; 234: 356-364, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31228837

RESUMEN

The potential of a novel anaerobic/aerobic algal-bacterial photobioreactor for the treatment of synthetic textile wastewater (STWW) was here assessed. Algal-bacterial symbiosis supported total organic carbon, nitrogen and phosphorous removal efficiencies of 78 ±â€¯2%, 47 ±â€¯2% and 26 ±â€¯2%, respectively, at a hydraulic retention time (HRT) of 8 days. A decrease in the HRT from 8 to 4 and 2 days resulted in a slight decrease in organic carbon and phosphate removal, but a sharp decrease in nitrogen removal. Moreover, an efficient decolorization of 99 ±â€¯1% and 96 ±â€¯3% for disperse orange-3 and of disperse blue-1, respectively, was recorded. The effective STWW treatment supported by the anaerobic/aerobic algal-bacterial photobioreactor was confirmed by the reduction in wastewater toxicity towards Raphanus sativus seed germination and growth. These results highlighted the potential of this innovative algal-bacterial photobioreactor configuration for the treatment of textile wastewater and water reuse.


Asunto(s)
Fotobiorreactores/microbiología , Textiles , Aguas Residuales/toxicidad , Purificación del Agua/métodos , Bacterias/metabolismo , Carbono/aislamiento & purificación , Chlorophyta/metabolismo , Color , Nitrógeno/aislamiento & purificación , Fósforo/aislamiento & purificación , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/análisis , Purificación del Agua/instrumentación
4.
Parasitology ; 146(7): 956-967, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30975235

RESUMEN

The essential oil (EO) of Thymus capitatus, seven fractions (F1-F7) obtained from silica gel chromatography, and several pure EO components were evaluated with respect to in vitro activities against Echinococcus multilocularis metacestodes and germinal layer (GL) cells. Attempts to evaluate physical damage in metacestodes by phosphoglucose isomerase (PGI) assay failed because EO and F1-F7 interfered with the PGI-activity measurements. A metacestode viability assay based on Alamar Blue, as well as transmission electron microscopy, demonstrated that exposure to EO, F2 and F4 impaired metacestode viability. F2 and F4 exhibited higher toxicity against metacestodes than against mammalian cells, whereas EO was as toxic to mammalian cells as to the parasite. However, none of these fractions exhibited notable activity against isolated E. multilocularis GL cells. Analysis by gas chromatography-mass spectrometry showed that carvacrol was the major component of the EO (82.4%), as well as of the fractions F3 (94.4%), F4 (98.1%) and F5 (90.7%). Other major components of EO were ß-caryophyllene, limonene, thymol and eugenol. However, exposure of metacestodes to these components was ineffective. Thus, fractions F2 and F4 of T. capitatus EO contain potent anti-echinococcal compounds, but the activities of these two fractions are most likely based on synergistic effects between several major and minor constituents.


Asunto(s)
Antihelmínticos/farmacología , Echinococcus multilocularis/citología , Echinococcus multilocularis/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Thymus (Planta)/química , Animales , Antihelmínticos/química , Bioensayo , Carcinoma Hepatocelular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatografía en Gel , Descubrimiento de Drogas , Equinococosis/tratamiento farmacológico , Fibroblastos/efectos de los fármacos , Prepucio/citología , Prepucio/efectos de los fármacos , Humanos , Masculino , Aceites Volátiles/química , Aceites de Plantas/química , Ratas
5.
Nat Prod Res ; 33(2): 280-286, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29533086

RESUMEN

From the butanolic and the ethyl acetate extracts of Rhamnus alaternus L root bark and leaves, three new anthraquinone glycosides, alaternosides A-C (1,4,6,8 tetrahydroxy-3 methyl anthraquinone 1-O-ß-D-glucopyranosyl-4,6-di-O-α-L-rhamnopyranoside (1); 1,2,6,8 tetrahydroxy-3 methyl anthraquinone 8-O-ß-D-glucopyranoside (2) and 1, 6 dihydroxy-3 methyl 6 [2'-Me (heptoxy)] anthraquinone (3)) were isolated and elucidated together with the two known anthraquinone glycosides, Physcion-8-O-rutinoside (4) and emodin-6-O-α-L-rhamnoside (5) as well as with the known kaempferol-7-methylether (6), ß-sitosterol (7) and ß-sitosterol-3-O-glycoside (8). Their chemical structures were elucidated using spectroscopic methods (1D-, 2D-NMR and FAB-MS). Free radical scavenging activity of the isolated compounds was evaluated by their ability to scavenge DPPH. free radicals. Compounds (3), (4) and (6) showed the highest activity with IC50 values of 9.46, 27.68 and 2.35 µg/mL, respectively.


Asunto(s)
Antraquinonas/aislamiento & purificación , Rhamnus/química , Antraquinonas/farmacología , Depuradores de Radicales Libres , Glicósidos/química , Glicósidos/aislamiento & purificación , Quempferoles , Estructura Molecular , Extractos Vegetales/química
6.
Nutr Cancer ; 70(4): 650-662, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29697283

RESUMEN

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 Xenoinjerto
7.
Cell Stress Chaperones ; 22(6): 775-785, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28578499

RESUMEN

Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing-prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-ß-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Flavonas/química , Glucósidos/química , Neoplasias/terapia , Fitoquímicos/química , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Flavonas/farmacología , Glucósidos/farmacología , Calefacción , Humanos , Factores Inmunológicos/química , Factores Inmunológicos/uso terapéutico , Inmunoterapia , Células Asesinas Naturales/efectos de los fármacos , Neoplasias/inmunología , Óxido Nítrico/metabolismo , Fitoquímicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Bazo/citología , Bazo/efectos de los fármacos
8.
Drug Chem Toxicol ; 40(4): 416-424, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27855523

RESUMEN

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 fluorescence of the DCF product. The study first results indicated that caffeic, 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 caffeic, 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/inmunología
9.
Microb Pathog ; 106: 50-59, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27815129

RESUMEN

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 fármacos
10.
Cell Stress Chaperones ; 21(5): 773-81, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27250501

RESUMEN

Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses against infection or to ameliorate immune-based pathologies. To determine whether eriodictyol has immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we investigated the stimulatory effect of eriodictyol on spleen cells isolated from BALB/c mice. Eriodictyol significantly stimulated splenocyte proliferation. However, only B lymphocytes (not T lymphocytes) could be stimulated by eriodictyol in a dose-related manner. Studies assessing potential effect of eriodictyol on innate immunity reported that eriodictyol enhanced significantly the killing activity of natural killer (NK) cells, T lymphocytes, and macrophages. We also demonstrated that eriodictyol inhibited nitric oxide (NO) production and lysosomal enzyme activity in murine peritoneal macrophages cultured ex-vivo, suggesting a potential anti-inflammatory effect in situ. Eriodictyol revealed also a cellular anti-oxidant activity in splenocytes and macrophages. Furthermore, eriodictyol increased catalase activity in spleen cells. From this data, it can be concluded that eriodictyol exhibited an immunomodulatory effect that could be ascribed in part to a cytoprotective effect related to its anti-oxidant activity.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Flavanonas/farmacología , Factores Inmunológicos/farmacología , Animales , Catalasa/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Óxido Nítrico/biosíntesis , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología
11.
Environ Toxicol Pharmacol ; 44: 44-52, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27105156

RESUMEN

The in vitro antioxidant, antigenotoxic and antiproliferative activities of Teucrium ramosissimum extracts were investigated. The antioxidant activities of the tested extracts were evaluated through three chemical assays: The Cupric reducing antioxidant capacity, the reducing power and the ferric reducing antioxidant power. TR1 fraction from methanol extract showed the best antioxidant activity evaluated by the CUPRAC, RP and FRAP assays with TEAC values of 4.04, 1.77 and 1.48µM respectively compared to control. Yet, TR2 fraction exhibited the lowest antioxidant effect with a TEAC values of 1.97, 0.408 and 0.35µM respectively. All the tested extracts were also found to be effective in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. Furthermore, the effects of T. ramosissimum extracts on cell proliferation were also examined. The cytotoxic study revealed that methanol extract significantly inhibited the proliferation of K562 cells (IC50=150µg/mL). The antigenotoxic properties of these extracts were investigated by assessing the induction and inhibition of the genotoxicity induced by the direct-acting mutagen, hydrogen peroxide (H2O2), using an eukaryotic system; the "Comet assay." The results showed that all the extracts inhibited the genotoxicity induced by H2O2, and particularly TR2 fraction (96.99%) and methanol extract (96.64%). The present study has demonstrated that T. ramosissimum extract possess potent antioxidant, antiproliferative and antigenotoxic activities, which could be derived from compounds such as flavonoids and polyphenols.


Asunto(s)
Antimutagênicos/farmacología , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Antimutagênicos/química , Antioxidantes/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Flavonoides/análisis , Humanos , Peróxido de Hidrógeno/toxicidad , Células K562 , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Mutágenos/toxicidad , Extractos Vegetales/química , Hojas de la Planta , Polifenoles/análisis , Teucrium/química
12.
Regul Toxicol Pharmacol ; 77: 117-24, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26946406

RESUMEN

Genotoxicity of Ceratonia siliqua extracts, was investigated by assessing their capacity to induce nucleus DNA degradation of murine leukaemia cells L1210, using the "Comet assay". The ability of total oligomer flavonoids (TOF) and aqueous extracts to protect cell DNA against oxidative stress induced by H2O2, was performed by pre- co or post-treatment of cells with the before mentioned extracts for different periods preceding exposure to H2O2 stress. No significant genotoxic effect was detected at different exposure times, except at the lowest concentration of TOF extract (16.25 µg/ml). It appears that extracts decreased DNA damage, induced by H2O2. Both of TOF and aqueous extracts exhibited cellular antioxidant capacity, with EC50 values of respectively <16.25 and < 35 µg/ml, as well as, a protective capacity against lipidperoxidation inducing using L1210 cells line as a cellular model. MDA inhibition percentages reached 88.43% and 90.52% with respectively 35.5 µg/ml of TOF extract and 70 µg/ml of aqueous extract. Antioxidant properties of carob leaf extracts revealed by our study make a good antioxidant protection and thus a good candidate as food addition component.


Asunto(s)
Antimutagênicos/farmacología , Antioxidantes/farmacología , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Leucemia/genética , Mutágenos/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antimutagênicos/aislamiento & purificación , Antimutagênicos/toxicidad , Antioxidantes/aislamiento & purificación , Antioxidantes/toxicidad , Biomarcadores/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fabaceae/química , Fabaceae/toxicidad , Peróxido de Hidrógeno/toxicidad , Leucemia/metabolismo , Leucemia/patología , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Ratones , Mutágenos/aislamiento & purificación , Mutágenos/toxicidad , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Plantas Medicinales , Medición de Riesgo
13.
Melanoma Res ; 26(3): 211-22, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26795272

RESUMEN

The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species in B16F10 and primary human keratinocyte cells. Our results indicate that hawthorn could be considered as a promising agent for the treatment of melanoma as it shows antitumor activity in vitro and in vivo. Moreover, hawthorn constituents are shown to be highly effective at inhibiting tyrosinase-mediated melanogenesis in vitro on melanoma cells by preventing oxidation in these cells and without affecting the viability of normal human keratinocyte cells. Then, hawthorn might also be used as a new candidate of natural skin depigmenting agents in skin care products.


Asunto(s)
Crataegus/química , Melanoma Experimental/tratamiento farmacológico , Extractos Vegetales/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Cromatografía Líquida de Alta Presión/métodos , Humanos , Queratinocitos/efectos de los fármacos , Masculino , Melanoma Experimental/patología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/aislamiento & purificación , Neoplasias Cutáneas/patología
14.
Drug Chem Toxicol ; 39(3): 297-302, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26582193

RESUMEN

Methanol extract of Daphne gnidium leaves was assessed for its antigenotoxic and neuroprotective effects through antioxidant and antibutyrylcholinesterase activities. Antigenotoxic activity was evaluated against methyl methanesulfonate injected intraperitoneally to mice, using the comet assay. The protective effect of D. gnidium reached 99.12%, at the lowest tested dose (44 mg/kg b.w.) in kidney cells, and 92.16% at the dose of 88 mg/kg b.w. in blood cells. The extract was dissolved in water and administrated to mice by intraperitoneal injection. Antioxidant activity was tested against DPPH radicals. It reached a maximum of 74.52% with an IC50 value of 45 µg/ml. Anticholinesterase activity was determined against butyrylcholinesterase, an enzyme linked to Alzheimer disease. The extract exhibited antibutyrylcholinestrase effect with an inhibition percentage of 35.82% at the lowest tested dose (44 mg/kg b.w.).


Asunto(s)
Antimutagênicos/farmacología , Daño del ADN/efectos de los fármacos , Daphne/química , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Antimutagênicos/aislamiento & purificación , Antimutagênicos/toxicidad , Compuestos de Bifenilo/química , Butirilcolinesterasa/sangre , Ensayo Cometa , Daño del ADN/genética , Relación Dosis-Respuesta a Droga , Inyecciones Intraperitoneales , Riñón/efectos de los fármacos , Riñón/patología , Dosificación Letal Mediana , Peroxidación de Lípido/efectos de los fármacos , Masculino , Metanol/química , Metilmetanosulfonato/toxicidad , Ratones , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/toxicidad , Picratos/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Pruebas de Toxicidad Aguda
15.
Tumour Biol ; 37(6): 7703-12, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26692099

RESUMEN

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 , Túnez
16.
Tumour Biol ; 37(5): 6511-7, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26637225

RESUMEN

The purpose of this study was to assess the antitumor and immunomodulatory effects of the aqueous extract from Daphne gnidium in mice-bearing melanoma tumor. Balb/C mice were subcutaneously implanted with B16-F10 cells and treated intraperitoneally with the aqueous extract at 200 mg/Kg b.w for 21 days. After euthanization on day 22, the tumors were weighed; lymphocyte proliferation, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell activities were evaluated using the MTT assay. Macrophage phagocytosis was studied by measuring the lysosomal activity. In addition to its potential to inhibit the growth of the transplantable tumor, the aqueous extract remarkably induced splenocyte proliferation and both NK and CTL activities in tumor-bearing mice. The aqueous extract was also seen to have promoted lysosomal activity of host macrophages.


Asunto(s)
Antineoplásicos/farmacología , Daphne/química , Sistema Inmunológico/efectos de los fármacos , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Lisosomas/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo
17.
J Cell Biochem ; 117(5): 1262-72, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26495895

RESUMEN

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/metabolismo
18.
Tumour Biol ; 37(6): 7967-80, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26711781

RESUMEN

The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.


Asunto(s)
Antioxidantes/farmacología , Crataegus/química , Inmunomodulación/efectos de los fármacos , Leucocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Cromatografía Líquida de Alta Presión , Células Asesinas Naturales/efectos de los fármacos , Macrófagos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico , Extractos Vegetales/aislamiento & purificación , Bazo/efectos de los fármacos , Linfocitos T Citotóxicos/efectos de los fármacos
19.
BMC Complement Altern Med ; 15: 300, 2015 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-26329604

RESUMEN

BACKGROUND: Here, phytochemical profile of Nitraria retusa (N. Retusa) leaf extracts was identified and their ability to induce apoptosis and inhibiting growth of melanoma cells and enhancing melanogenesis of B16F10 melanoma was evaluated. METHODS: The Apoptosis was evidenced by investigating DNA fragmentation, and Acridine orange/ethidium bromide staining. Amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. RESULTS: Extracts from Nitraria retusa exhibited significant anti-proliferative activity after 48 h of incubation. Our result was confirmed by ladder DNA fragmentation profile. All extracts showed also the ability to enhance melanogenesis and tyrosinase activity of B16F10 melanoma cells. CONCLUSION: The tested extracts have a significant biological effect which may be due to their bioactive compounds.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Magnoliopsida/química , Melanoma Experimental/metabolismo , Extractos Vegetales/farmacología , Animales , Línea Celular Tumoral , Ratones , Hojas de la Planta/química
20.
Pharm Biol ; 53(12): 1786-94, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25880139

RESUMEN

CONTEXT: The leaves of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) are used in traditional medicine to treat inflammatory diseases. However, information about the antigenotoxic and antioxidant properties of its leaves remains to be elucidated. OBJECTIVE: The objective of this work was to evaluate the mutagenic/antimutagenic, genotoxic/antigenotoxic, and antioxidant potentials of aqueous and total oligomers flavonoid (TOF) extracts from E. japonica. MATERIALS AND METHODS: The mutagenic/antimutagenic and genotoxic/antigenotoxic potentials of extracts (50, 250, and 500 µg/plate) were evaluated, respectively, by the Ames test with 48 h incubation and the SOS chromotest test with 2 h incubation. The antioxidant capacity of these extracts (ranging from 50 to 700 µg/mL) was tested using xanthine/xanthine oxidase and the deoxyribose assays. RESULTS: Eriobotrya japonica extracts showed neither mutagenic nor genotoxic effect. The highest protective effect against methyl methanesulfonate and 2-aminoanthracene was obtained in the presence of aqueous extract, with IC50 values of 80 and 140 µg/plate, respectively, against S. typhimurium TA104. Moreover, this extract (500 µg/plate) was also able to reduce significantly the genotoxicity induced by nitrofurantoin and aflatoxin B1 with IC50 values of 140 and 240 µg/assay, respectively. Likewise, aqueous and TOF extracts inhibited xanthine oxidase and superoxide anion formation with IC50 values ranging from 45 to 95 and from 70 to 90 µg/mL, respectively. However, TOF extract is more efficient in inhibiting hydroxyl radical and chelating iron ion with IC50 values of 140 and 400 µg/mL, respectively, when compared with the aqueous extract. CONCLUSION: Eriobotrya japonica prevents the genotoxicity of some carcinogenic substances probably thanks to its antioxidant capacities.


Asunto(s)
Antimutagênicos/farmacología , Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Eriobotrya , Extractos Vegetales/farmacología , Hojas de la Planta , Antimutagênicos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Daño del ADN/fisiología , Evaluación Preclínica de Medicamentos/métodos , Depuradores de Radicales Libres/metabolismo , Extractos Vegetales/aislamiento & purificación , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/metabolismo
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