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 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
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/químicaRESUMEN
The objectives of this study were to evaluate the in vitro and in vivo anti-tumor potential of the aqueous gall extract (G extract) from Limoniastrum guyonianum and to elucidate its immunological mechanisms, in part, by assessing its effects on the growth of transplanted tumors and the immune response in these tumor-bearing mice. Here, mice were inoculated with B16F10 mouse tumor cells and then treated intraperitoneally with G extract at 25 or 50 mg extract/kg BW for 7, 14, or 21 days. At each timepoint, effects of the extract on the tumor growth, splenocytes proliferation, NK cell activity, and CTL activity among splenocytes isolated from the mice were measured. G extract-induced tumor growth inhibition was associated with characteristic apoptotic changes in the tumor cells, like nuclear condensation. In addition, the extract inhibited melanin synthesis and tyrosinase activity among melanoma cells in a concentration-related manner. G extract did not only significantly inhibit the growth of the transplantable tumor, but also remarkably increased splenocytes proliferation and both NK and CTL activities in tumor-bearing mice. The extract was also seen to have promoted lysosomal activity of host macrophages and gave rise to enhanced cellular anti-oxidant activity in several cell types in mice.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Factores Inmunológicos/farmacología , Melanoma Experimental/tratamiento farmacológico , Extractos Vegetales/farmacología , Plumbaginaceae/química , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Melaninas/biosíntesis , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones Endogámicos BALB C , Monofenol Monooxigenasa/metabolismo , Linfocitos T Citotóxicos/efectos de los fármacosRESUMEN
OBJECTIVE@#To evaluate in vitro antioxidant and apoptotic activities of Cyperus rotundus (C. rotundus).@*METHODS@#The phytochemical study and the antioxidant activities of both methanol and aqueous extracts from C. rotundus aerial part were determined. In addition, these extracts were also investigated for their cytotoxic and apoptotic activities. The major compound of the methanol extract was isolated. Both methanol and aqueous extracts (300, 150, and 50 μg/mL) were evaluated for their antioxidant activity by the xanthine/xanthine oxidase assay system. However, 16, 8, and 4 mg/mL of each extract were tested to investigate their OH. formation scavenging potential. Aqueous extract (800, 400, and 200 μg/mL) and methanol extract (350, 175, and 88 μg/mL) were tested against lipid peroxidation, induced by 75 μM H2O2. The cytotoxicity (by MTT assay) and cell DNA fragmentation of both extracts were evaluated towards K562 and L1210 cell lines. The major compound was obtained from the butanol fraction of methanol extract and its structure was determined by RMN spectroscopic analysis.@*RESULTS@#The methanol and aqueous extracts showed respectively, 88% and 19% inhibition of xanthine oxidase activity. Yet, the same extracts inhibited lipid peroxidation by 61.5% and 42.0%, respectively. Both extracts inhibited OH. formation by 27.1% and 25.3%, respectively. Only methanol extract induced DNA degradation. Orientin was determined as the major compound isolated from the butanol fraction of methanol extract.@*CONCLUSIONS@#It appears that C. rotundus extracts exhibit a potential use as a natural antioxidant and an apoptosis inducer.
Asunto(s)
Humanos , Antioxidantes , Química , Metabolismo , Farmacología , Apoptosis , Proliferación Celular , Cyperus , Química , Flavonoides , Glucósidos , Células K562 , Peroxidación de Lípido , Extractos Vegetales , Química , Farmacología , Polifenoles , Química , Farmacología , Xantina Oxidasa , MetabolismoRESUMEN
Fractionation of the chloroformic extracts from Teucrium ramosissimum leaves resulted in the isolation of three flavonoids: genkwanin (1), cirsimaritin (2) and 4',7-dimethoxy apigenin (4) and one sesquiterpene: ß-eudesmol (3). The structures were determined using data obtained from (1)H and (13)C NMR spectra, as well as by various correlation experiments (COSY, HMQC and HMBC). The antioxidant activities of the isolated flavonoids from T. ramosissimum leaves were evaluated by measuring their ability to scavenge the radical ABTS(+) and through chemical assays: cupric reducing antioxidant capacity (CUPRAC), reducing power (RP) and ferric reducing antioxidant power (FRAP). Furthermore, the effects of T. ramosissimum isolated molecules, on inhibition of cell proliferation and induction of apoptosis in human leukemia cells, were also examined. Cirsimaritin showed the best activity in the ABTS assay with TEAC value 2.04µM, whereas apigenin and 4',7-dimethoxy apigenin exhibited the highest antioxidant activity using the CUPRAC, RP and FRAP assays with TEAC values 10.5, 1.39 and 0.71µM respectively. The cytotoxic activity revealed that the ß-eudesmol inhibited significantly the proliferation of K562 cells (IC(50)=20µg/ml).