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1.
Nutr Cancer ; 73(2): 329-338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32270711

RESUMO

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.


Assuntos
Flavonas , Mitomicina , Animais , Dano ao DNA , Flavonoides , Camundongos , Camundongos Endogâmicos BALB C , Mitomicina/toxicidade , Estresse Oxidativo
2.
Parasitology ; 146(7): 956-967, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30975235

RESUMO

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.


Assuntos
Anti-Helmínticos/farmacologia , Echinococcus multilocularis/citologia , Echinococcus multilocularis/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Thymus (Planta)/química , Animais , Anti-Helmínticos/química , Bioensaio , Carcinoma Hepatocelular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia em Gel , Descoberta de Drogas , Equinococose/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Humanos , Masculino , Óleos Voláteis/química , Óleos de Plantas/química , Ratos
3.
Regul Toxicol Pharmacol ; 107: 104404, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31199997

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ericaceae , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Fenofibrato/uso terapêutico , Hiperlipidemias/induzido quimicamente , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Folhas de Planta , Polietilenoglicóis , Ratos Wistar
4.
Nutr Cancer ; 70(4): 650-662, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29697283

RESUMO

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.


Assuntos
Fatores Imunológicos/farmacologia , Magnoliopsida/química , Ácido Palmítico/farmacologia , Extratos Vegetais/farmacologia , Sitosteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Clorofórmio/química , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Tunísia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Microb Pathog ; 106: 50-59, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27815129

RESUMO

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.


Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Amoxicilina/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Monoterpenos Bicíclicos , Linhagem Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Cicloexenos/química , Combinação de Medicamentos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Queratinócitos/efeitos dos fármacos , Limoneno , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana/métodos , Monoterpenos/química , Novobiocina/farmacologia , Ofloxacino/farmacologia , Óleos Voláteis/química , Oxacilina/farmacologia , Piperacilina/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Óleos de Plantas/química , Sesquiterpenos de Eudesmano/química , Baço/efeitos dos fármacos , Terpenos/química , Tetraciclina/farmacologia , Fatores de Tempo , beta-Lactamases/efeitos dos fármacos
6.
Drug Chem Toxicol ; 40(4): 416-424, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27855523

RESUMO

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.


Assuntos
Antioxidantes/metabolismo , Ácidos Cafeicos/metabolismo , Ácidos Cumáricos/metabolismo , Fatores Imunológicos/metabolismo , Células Matadoras Naturais/metabolismo , Propionatos/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Antioxidantes/efeitos adversos , Antioxidantes/química , Ácidos Cafeicos/efeitos adversos , Ácidos Cafeicos/química , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ácidos Cumáricos/efeitos adversos , Ácidos Cumáricos/química , Suplementos Nutricionais/efeitos adversos , Imunidade Celular , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/química , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Ativação Linfocitária/efeitos dos fármacos , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Mitógenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Propionatos/efeitos adversos , Propionatos/química , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Relação Estrutura-Atividade , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
7.
J Cell Biochem ; 117(5): 1262-72, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26495895

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Crataegus/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Acetatos/química , Antineoplásicos/farmacologia , Western Blotting , Caspase 8/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HCT116 , Células HT29 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Poli(ADP-Ribose) Polimerase-1/metabolismo
8.
Tumour Biol ; 37(6): 7703-12, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26692099

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Teucrium/química , Animais , Antioxidantes/isolamento & purificação , Apigenina/isolamento & purificação , Apigenina/farmacologia , Células Cultivadas/efeitos dos fármacos , Endotoxinas/farmacologia , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonas/isolamento & purificação , Flavonas/farmacologia , Fatores Imunológicos/isolamento & purificação , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Lisossomos/enzimologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Plantas Medicinais/química , Mitógenos de Phytolacca americana/farmacologia , Proteínas Inativadoras de Ribossomos/farmacologia , Organismos Livres de Patógenos Específicos , Linfócitos T Citotóxicos/imunologia , Tunísia
9.
Tumour Biol ; 37(8): 11349-58, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26960691

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Esculina/farmacologia , Melanoma Experimental/imunologia , Neoplasias Cutâneas/imunologia , Animais , Citotoxicidade Imunológica/imunologia , Fatores Imunológicos/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
10.
Tumour Biol ; 37(3): 3657-64, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26459313

RESUMO

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.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Esculina/farmacologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dimerização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Esculina/química , Glioblastoma/irrigação sanguínea , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Integrina alfa2beta1/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/prevenção & controle , Receptores de Vitronectina/metabolismo
11.
Tumour Biol ; 37(5): 6571-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26638168

RESUMO

Flavonoids impart a variety of biological activities, including anti-oxidant, anti-inflammatory, and anti-genotoxic effects. This study investigated the effects of flavone luteolin and apigenin on immune cell functions, including proliferation, natural killer (NK) cell activity, and cytotoxic T lymphocyte (CTL) activity of isolated murine splenocytes. We report for the first time that flavones enhance lymphocyte proliferation at 10 µM. Luteolin and apigenin significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation and enhance humoral immune responses. Luteolin induces a weak cell proliferation of lectin-stimulated splenic T cells, when compared to apigenin. In addition, both flavones significantly enhance NK cell and CTL activities. Furthermore, our study demonstrated that both flavones could inhibit lysosomal enzyme activity, suggesting a potential anti-inflammatory effect. The anti-inflammatory activity was concomitant with the cellular anti-oxidant effect detected in macrophages, red blood cells, and splenocytes. We conclude from this study that flavones exhibited an immunomodulatory effect which could be ascribed, in part, to its cytoprotective capacity via its anti-oxidant activity.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Flavonas/química , Fatores Imunológicos/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Eritrócitos/metabolismo , Flavonas/farmacologia , Fatores Imunológicos/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Lisossomos/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Relação Estrutura-Atividade , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo
12.
Tumour Biol ; 37(6): 7967-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26711781

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Crataegus/química , Imunomodulação/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico , Extratos Vegetais/isolamento & purificação , Baço/efeitos dos fármacos , Linfócitos T Citotóxicos/efeitos dos fármacos
13.
Tumour Biol ; 37(5): 6511-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26637225

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Daphne/química , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Lisossomos/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo
14.
Regul Toxicol Pharmacol ; 82: 48-52, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27825835

RESUMO

Mitomycin C is one of the most effective chemotherapeutic drugs against various solid tumors. However, despite its wide spectrum of clinical benefits, this agent is capable of inducing various types of genotoxicity. In this study, we investigated the effect of esculin and its oligomer fractions (E1, E2 and E3) against mitomycin C induced genotoxicity in liver and kidney cells isolated from Balb/C mice using the comet assay. Esculin and its oligomer fractions were not genotoxic at the tested doses (20 mg/kg and 40 mg/kg b.w). A significant decrease in DNA damages was observed, suggesting a protective role of esculin and its oligomer fractions against the genotoxicity induced by mitomycin C on liver and kidney cells. Moreover, esculin and its oligomer fractions did not induce an increase of malondialdehyde levels.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Esculina/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Mitomicina/toxicidade , Animais , Antimutagênicos/toxicidade , Relação Dose-Resposta a Droga , Esculina/toxicidade , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos
15.
Regul Toxicol Pharmacol ; 77: 117-24, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26946406

RESUMO

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.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Leucemia/genética , Mutagênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antimutagênicos/isolamento & purificação , Antimutagênicos/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/toxicidade , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fabaceae/química , Fabaceae/toxicidade , Peróxido de Hidrogênio/toxicidade , Leucemia/metabolismo , Leucemia/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Camundongos , Mutagênicos/isolamento & purificação , Mutagênicos/toxicidade , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Medição de Risco
16.
Drug Chem Toxicol ; 39(3): 297-302, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26582193

RESUMO

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.).


Assuntos
Antimutagênicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Daphne/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antimutagênicos/isolamento & purificação , Antimutagênicos/toxicidade , Compostos de Bifenilo/química , Butirilcolinesterase/sangue , Ensaio Cometa , Dano ao DNA/genética , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metanol/química , Metanossulfonato de Metila/toxicidade , Camundongos , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/toxicidade , Picratos/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda
17.
Tumour Biol ; 36(7): 5165-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25663463

RESUMO

Many studies have been performed to assess potential utility of natural products as immunomodulants to enhance antitumor activity in situ. In this study, an essential oil (EO) from the aerial parts of Pituranthos tortuosus was prepared using hydrodistillation, its composition was characterized, and its immunomodulatory potential was assessed. The results indicated that the EO contained sabinene, α-pinene, limonene, and terpinen-4-ol as major constituents. EO was also found to be able to significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation, suggestive of a potential for activation of B cells and enhanced humoral immune responses in hosts given this product. Effects of EO on cell proliferation and apoptosis were also investigated in B16F10 melanoma cells. EO-induced tumor cell growth inhibition was associated with characteristic apoptotic changes in the cells, including nuclear condensation. 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.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Imunomodulação/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Óleos Voláteis/administração & dosagem , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Imunidade Humoral/efeitos dos fármacos , Melanoma Experimental/patologia , Camundongos , Óleos Voláteis/química , Baço/efeitos dos fármacos , Baço/imunologia
18.
Cancer Cell Int ; 15: 82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26309426

RESUMO

BACKGROUND: The purpose of this study was to assess the antitumoral effect of the methanol extract (MeOH) from Nitraria retusa leaves and to investigate its immunomodulatory activity that mediated the prevention of tumor progression in tumor-bearing mice. METHODS: Balb/c mice weighing 18-20 g were subcutaneously implanted with B16-F10 cells then injected intra-peritoneally, 7 days later with (200 mg/kg bw) of MeOH extract, for 21 days. After euthanization on day 21, the tumors were weighed. Lymphocyte proliferation, cytotoxic T lymphocyte (CTL) and NK activity were evaluated using the MTT assay. Macrophage phagocytosis was studied by measuring their lysosomal activity and nitric oxide production. RESULTS: The methanol extract inhibited significantly the growth of the implanted tumor, and increased remarkably splenocyte proliferation as well as NK and CTL activities, in tumor-bearing mice. It also promoted lysosomal activity of treated animal macrophages. CONCLUSION: Our findings suggest that antitumoral effect of MeOH extract is related with to immunomodulatory activity.


INTRODUCTION: Le but de cette étude est d'évaluer l'effet antitumoral de l'extrait méthanolique (MeOH) issue des feuilles de N. retusa via son potentiel immunomodulateur et sa capacité à prévenir la progression tumoral chez des souris porteuses de tumeurs. MÉTHODES: Pour cette étude, nous avons implanté par voie sous-cutanée, chez des souris Balb/c de 18 à 20 g, des cellules B16-F10. Après apparition de la tumeur, au bout de 7jours de l'injection de B16-F10, nous avons entamé un traitement par injection intrapéritonéale de 200 mg/kg de poids corporel, d'extrait MeOH, et ce durant 21 jours. Les animaux sont euthanasiés au 21ème jour, et les tumeurs sont pesées. La prolifération des splénocytes et des lymphocytes T cytotoxiques (CTL) à été évalué à l'aide du test au MTT. L'évaluation de l'activité NK à également été effectuée à l'aide du par le même test. Dans un second volet, nous avons étudié l'activité phagocytaire des macrophages en évaluant leur activité lysosomale et la production d'oxyde nitrique. RÉSULTATS: L'extrait MeOH révèle, un fort potentiel inhibiteur de la croissance de la tumeur transplantée, une augmentation de façon remarquable de la prolifération des splénocytes ainsi qu'une forte induction des activités NK et CTL chez des souris porteuses de tumeurs. Aussi l'extrait a considérablement induit l'activité phagocytaire des macrophages en augmentant leur activité lysosomale ainsi que la production de monoxide d'azote, par ces cellules. CONCLUSION: Nos résultats suggèrent fortement que l'effet antitumoral de l'extrait méthanolique passe par son potentiel immunomodulatrice.

19.
BMC Complement Altern Med ; 15: 300, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26329604

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Magnoliopsida/química , Melanoma Experimental/metabolismo , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral , Camundongos , Folhas de Planta/química
20.
Drug Chem Toxicol ; 38(1): 84-91, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24724833

RESUMO

Evaluation of the immunomodulatory activity of plant extracts is an interesting and growing area of research. In this study, effects of a methanolic extract of Limoniastrum guyonianum stems (M extract) on mice immune cell function in vitro were investigated. These studies showed that mitogen-induced lymphocyte proliferation was dose-dependently inhibited by the extract. Further, the lectin-induced response appeared to be more sensitive to the suppressive effects of the extract than were LPS-stimulated responses. In studies to assess any potential effects of extract on innate immunity, the results showed that the extract significantly enhanced the killing activity of isolated NK cells. In addition, studies here demonstrated that the extract could enhance lysosomal enzyme activity and inhibit nitrite oxide (NO) production by murine peritoneal macrophages ex vivo, suggesting a potential anti-inflammatory effect in situ. The anti-inflammatory activity was concomitant with the cellular anti-oxidant effect in macrophages and splenocytes.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/metabolismo , Fatores Imunológicos/farmacologia , Linfócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plumbaginaceae/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/isolamento & purificação , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Metanol/química , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Extratos Vegetais/isolamento & purificação , Caules de Planta/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo
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