RESUMEN
Yerba mate tea (YMT) has a chemopreventive role in a variety of inflammatory diseases. The objective was to determine the capability of YMT and mate saponins to prevent azoxymethane (AOM)-induced colonic inflammation in rats. YMT (2% dry leaves, w/v, as a source of drinking fluid) (n = 15) and mate saponins (0.01% in the diet, at a concentration present in one cup of YMT) (n = 15) were given ad libitum to rats 2 weeks prior to AOM-injection until the end of the study; while control rats (n = 15) received a basal diet and drinking water. After 8-weeks of study, total colonic mucosa was scraped (n = 3 rats/group) and the remaining colons (n =12 rats/group) were cut into three equal sections and aberrant crypt foci (ACF) were analyzed. YMT reduced ACF formation from 113 (control group) to 89 (P < 0.05). YMT and mate saponins reduced the expression of proinflammatory molecules COX-2 and iNOS with concomitant reduction in p-p65 (P < 0.05). Immunohistochemical analysis of the formalin-fixed middle colons showed that YMT and mate saponins reduced the expression of p-p65(ser311) by 45.7% and 43.1%, respectively, in comparison to the control (P < 0.05). In addition, the expression of molecules upstream of NF-κB such as p-IκB-α and p-GSK-3ß(Y216) was downregulated by YMT 24.7% and 24.4%, respectively (P < 0.05). Results suggest the mechanism involved in the chemopreventive effect of YMT and mate saponin consumption in AOM induced-colonic inflammation in rats is through inhibition of NF-κB.
Asunto(s)
Antiinflamatorios/farmacología , Colitis/prevención & control , Ilex paraguariensis/química , Extractos Vegetales/farmacología , Saponinas/farmacología , Transducción de Señal , Animales , Antiinflamatorios/uso terapéutico , Anticarcinógenos/farmacología , Anticarcinógenos/uso terapéutico , Azoximetano , Bebidas , Colitis/inducido químicamente , Colon/efectos de los fármacos , Colon/inmunología , Colon/patología , Neoplasias Colorrectales/prevención & control , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Proteínas I-kappa B/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Masculino , Inhibidor NF-kappaB alfa , Proteínas de Neoplasias/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Fosforilación , Extractos Vegetales/uso terapéutico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Procesamiento Proteico-Postraduccional , Ratas , Ratas Endogámicas F344 , Saponinas/uso terapéuticoRESUMEN
SCOPE: The biological functions of caffeoylquinic acid (CQA) derivatives from various plant sources have been partially elucidated. The objectives were to isolate and purify diCQAs from Yerba mate tea leaves and assess their anti-inflammatory and anti-cancer capabilities in vitro and explore their mechanism of action. METHODS AND RESULTS: Methanol extracts of dried mate leaves were resolved by flash chromatography and further purified resulting in two fractions one containing 3,4- and 3,5-diCQAs and the other 4,5-diCQA with NMR-confirmed structures. Both fractions inhibited LPS-induced RAW 264.7 macrophage inflammation by suppressing nitric oxide/inducible nitric oxide and prostaglandin E(2) /cyclooxygenase-2 pathways through inhibiting nucleus translocation of Nuclear factor κB subunits, p50 and p65. The diCQA fractions inhibited Human colon cancer cells CRL-2577 (RKO) and HT-29 cell proliferation by inducing apoptosis in a time- and concentration-dependent manner, but did not affect the protein levels of p21, p27, p53, and Bax:Bcl-2 ratio in RKO cells. In HT-29 cells, however, the diCQA fractions increased Bax:Bcl-2 ratio. The diCQA fractions increased the activation of caspase-8 leading to cleavage of caspase-3 in both RKO and HT-29 colon cancer cells. CONCLUSION: The results suggest that diCQAs in Yerba mate could be potential anti-cancer agents and could mitigate other diseases also associated with inflammation.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Ácido Clorogénico/análogos & derivados , Ilex paraguariensis/química , Macrófagos/efectos de los fármacos , FN-kappa B/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Núcleo Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/farmacología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Evaluación Preclínica de Medicamentos , Activación Enzimática , Células HT29 , Humanos , Lipopolisacáridos/toxicidad , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/farmacología , Hojas de la Planta/química , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Yerba mate tea ( Ilex paraguariensis ) is growing in popularity around the world. The objective of this study was to investigate the potential anti-inflammatory effect of yerba mate tea (MT) extracts as well as some of its phytochemicals and their interactions. MT and decaffeinated MT extracts [1-300 microM chlorogenic acid (CHA) equiv]; CHA, caffeine from MT (matein), and mate saponins (1-300 microM); quercetin (1-200 microM); and ursolic and oleanolic acids (1-100 microM) were tested by measuring their ability to inhibit COX-2/PGE(2) and iNOS/NO pathways in LPS-induced RAW 264.7 macrophages. Mate saponins (IC(50) = 20 microM) and oleanolic acid (IC(50) = 80 microM) significantly inhibited iNOS/NO pathways, whereas ursolic acid showed low or no inhibition at 100 microM. Quercetin was the most potent inhibitor of pro-inflammatory responses at a concentration 10 times lower than the concentrations used of other compounds (IC(50) = 11.6 microM for NO, 7.9 microM for iNOS, and 6.5 microM for PGE(2)). Combination of quercetin/mate saponins (0.001:0.004, molar ratio) resulted in synergistic interaction inhibiting both NO and PGE(2) production. It also suppressed IL-6 and IL-1beta production and resulted in reduction of LPS-induced nuclear translocation of nuclear factor-kappaB subunits. MT extract did not have a potent anti-inflammatory effect perhaps due to the antagonistic effect of some of its compounds. However, whole MT consumption still has a promising anti-inflammatory outcome mainly through the PGE(2)/COX-2 pathway. To the authors' knowledge, this is the first study demonstrating the efficacy, interactions, and mechanisms of some MT phytochemicals in inhibiting pro-inflammatory responses.
Asunto(s)
Inhibidores de la Ciclooxigenasa 2/farmacología , Ilex paraguariensis/química , Macrófagos/enzimología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Quercetina/farmacología , Saponinas/farmacología , Animales , Bebidas/análisis , Línea Celular , Dinoprostona/antagonistas & inhibidores , Sinergismo Farmacológico , Inhibidores Enzimáticos/farmacología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/químicaRESUMEN
Tea is one of the most widely consumed beverages worldwide. Several studies have suggested that catechins and theaflavins found in tea may reduce the risk of various types of cancers. Major advances have been made to understand the molecular events leading to cancer prevention; however, the evidence is not conclusive. Evidence from pre-clinical and clinical studies also suggests that persistent inflammation can progress to cancer. Several possible mechanisms of action may explain the cancer preventive aspects of tea components specifically anti-inflammatory effects. In regards to brain health, green tea catechins have been recognized as multifunctional compounds for neuroprotection with beneficial effects on vascular function and mental performance. Theanine, a unique amino acid in tea, enhances cognition in humans and has neuroprotective effects. Human interventional studies with well characterized tea products are needed.