RESUMEN
In this study, a turmeric polysaccharide (TP-0) was isolated through hot water extraction and ethanol precipitation to produce a novel active polysaccharide from turmeric other than curcuminoids. TP-0 was found to be primarily composed of eight different monosaccharides, such as galactose (15.9%), galacturonic acid (15.2%), arabinose (11.4%), and rhamnose (9.7%), which are typical rhamnogalacturonan (RG)-I sugars. When stimulated with TP-0, peritoneal macrophages secreted a variety of immunostimulatory cytokines. In addition, intravenous and oral administration of TP-0 significantly enhanced the natural killer (NK) cells and cytotoxic T lymphocyte (CTL)-mediated cytotoxicity against tumor cells. In an assay for lung cancer induced by Colon26-M3.1 carcinoma, prophylactic intravenous and oral administration of TP-0 effectively inhibited lung cancer. These findings reveal that TP-0, a typical RG-I-type polysaccharide that is isolated from turmeric, has potent anti-metastatic activities, and these activities are linked to various immunological factors such as macrophages, NK cells, and CTL. PRACTICAL APPLICATIONS: Many studies related with turmeric have only focused that a curcuminoid of turmeric has beneficial effects on human health system. Nevertheless, in this study, it was confirmed that polysaccharide isolated from turmeric showed potent anti-cancer effects via activities of various immunological factors such as macrophages, NK cells, and CTL. These results suggest the high potential for development value of turmeric as a new candidate for immunostimulating-related health functional food ingredients.
Asunto(s)
Ingredientes Alimentarios , Neoplasias Pulmonares , Arabinosa , Curcuma , Citocinas , Diarilheptanoides , Etanol , Galactosa , Humanos , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Ramnogalacturonanos , Ramnosa , AguaRESUMEN
Determining the structure of REPI, an immunostimulatory polysaccharide fraction from radish leaves, is an important health objective. Herein, we show that REP-I contains nine different monosaccharides, including GalA (22.2%), Gal (32.6%), Ara (27.5%), and Rha (10.2%) as main sugars. REP-I was also reacted with ß-glucosyl Yariv reagent (29.8%), suggesting the presence of the arabino-ß-3,6-galactan. Furthermore, methylated-product analysis revealed that REP-I contains 13 different glycosyl linkages, including 4-linked GalpA (21.0%), 2,4-linked Rhap (7.0%), 4-linked Galp (5.8%), 5-linked Araf (10.1%), and 3,6-linked Galp (7.9%), which are characteristic of RG-I. Microstructural information was obtained by sequential degradation using four linkage-specific glycosylases and ß-elimination, with fragments analyzed on the basis of sugar composition, methylation, and MS/MS spectra. The results show that the immunostimulatory activity of REP-I is possibly due to the structure of RG-I, which is composed of a main chain with repeating [â2)-Rhap-(1 â 4)-GalpA-(1â] linkage units and three side-chains: a branched α(1 â 5)arabinan, a ß(1 â 4)galactan, and arabino-ß-3,6-galactan, which are branched at the C(O)4 position of each Rha residue in the REP-I main chain.
Asunto(s)
Raphanus , Secuencia de Carbohidratos , Galactanos/análisis , Pectinas/química , Hojas de la Planta/química , Polisacáridos/química , Ramnogalacturonanos , Espectrometría de Masas en TándemRESUMEN
The present study investigated the effect of high-temperature-processed green tea extract (HTP_GTE) and its bioactive components on the reduction of reactive oxygen species (ROS) and amyloid-beta (Aß) protein in human microvascular endothelial cells. Compared to Aß1-42-only treatment, pretreatment of HTP_GTE was revealed to effectively inhibit ROS generation (P<0.05). HTP_GTE and catechins not only inhibit Aß1-42 fibril formation but also destabilize preformed Aß1-42 fibrils. The presence of HTP_GTE, Aß1-42 fibril formation was significantly inhibited in a dose-dependent manner at 12.5-100 µg/ml of HTP_GTE, showing 86-56%, respectively. Treatment of various concentrations of HTP_GTE and catechins steadily destabilized the preformed Aß1-42 fibrils for 24â h in a dose-dependent manner. It was observed that the gallated groups such as epigallocatechin gallate, epicatechin gallate, gallocatechin gallate, and catechin gallate more effectively disturbed Aß1-42 fibril formation and destabilized the preformed Aß1-42 fibrils than the non-gallated group. Taken together, these findings supported that sterilized green tea could be promising natural anti-amyloidogenic agents associated with therapeutic approaches in Alzheimer's disease by scavenging ROS generation and Aß fibril in the brain tissue.
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Péptidos beta-Amiloides/metabolismo , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Camellia sinensis/química , Catequina/administración & dosificación , Fragmentos de Péptidos/metabolismo , Extractos Vegetales/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Amiloide/efectos de los fármacos , Encéfalo/irrigación sanguínea , Catequina/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Calor , Humanos , Microvasos/efectos de los fármacos , Agregación Patológica de Proteínas/metabolismo , TéRESUMEN
Graviola leaves contain much vitamin U (vit U), but their sensory quality is not good enough for them to be developed as food ingredients. Addition of excipient natural ingredients formulated alongside vit U as active ingredients could enhance not only its sensory quality but also its bioavailability. The objectives of this study were to measure the bioaccessibility and intestinal cellular uptake of bioactive components, including rutin, kaempferol-rutinoside, and vit U, from steamed extract of graviola leaves (SGV) and SGV enriched with kale extract (SGK), and to examine how much they can detoxify nicotine in HepG2 cells. The bioaccessibility of vit U from SGV and SGK was 82.40% and 68.03%, respectively. The cellular uptake of vit U in SGK by Caco-2 cells was higher than that in SGV. Cotinine content converted from nicotine in HepG2 cells for 120 min was 0.22 and 0.25 µg/mg protein in 50 µg/mL of SGV and SGK, respectively, which were 2.86 and 3.57 times higher than the no-treatment control. SGK treatment of HepG2 cells upregulated CYP2A6 three times as much as did that of SGV. Our results suggest that graviola leaf extract enriched with excipient ingredients such as kale could improve vit U absorption and provide a natural therapy for detoxifying nicotine.
Asunto(s)
Annona/química , Inactivación Metabólica/efectos de los fármacos , Absorción Intestinal/fisiología , Nicotina/metabolismo , Extractos Vegetales , Vitamina U , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacocinética , Extractos Vegetales/farmacología , Vitamina U/química , Vitamina U/metabolismo , Vitamina U/farmacocinética , Vitamina U/farmacologíaRESUMEN
BACKGROUND: This study aimed to investigate the profiles of bioactive components in roasted Lycium chinense leaves (LCLs) and its in vitro anti-obesity activity after digestion processes. RESULTS: Chlorogenic acid, kaempferol-3-sophoroside-7-glucoside, kaempferol-3-sophoroside, and kaempferol-3-glucoside were discovered as bioactive components in various ratios of ethanol (EtOH) extract in LCLs by using ultra-performance liquid chromatography-electrospray ionization-mass spectrophotometry (UPLC-ESI-MS). The roasting process followed by a 30% EtOH extraction tended to decrease the content of chlorogenic acid and kaempferol-3-glucoside, and enhanced the content of kaempferol-3-sophoroside-7-glucoside. It effectively inhibited pancreatic lipase activity by 62.50 ± 4.81%, which was approximately 1.71 percentage points higher than that of the dried-nonroasted LCL extract (60.79 ± 3.75%). Its bioaccessible fraction obtained from in vitro digestion significantly and dose dependently reduced intracellular lipid accumulation by adipocyte 3T3-L1 compared with a 30% EtOH extraction. At a concentration of 200 µg mL-1 , it inhibited lipid accumulation up to 29.55% in 3T3-L1 cells, which indicated that human digestive enzymes converted kaempferol-3-sophoroside-7-glucoside to kaempferol metabolites that have anti-obesity effects. CONCLUSION: This study suggests that the profiling of bioactive components by processing methods and a bioaccessible fraction could be crucial to improve the bioactivity of LCLs, and potentially be a natural anti-obesity ingredient after oral intake. © 2019 Society of Chemical Industry.
Asunto(s)
Fármacos Antiobesidad/química , Fármacos Antiobesidad/farmacología , Lycium/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Fármacos Antiobesidad/aislamiento & purificación , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Lipasa/química , Ratones , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/químicaRESUMEN
Two bioconversions were applied to green tea extracts (GTE) and flavonol glycoside rich fraction (FVNg) derived from insoluble green tea extract by tannase and cellulase treatment in order to obtain gallated catechins (EnzGTE) and flavonol aglycone rich fraction (FVNa), respectively. The bioaccessibility of epicatechins from GTE increased with the addition of FVNg, FVNa, and flavonol aglycone rich fraction of commercial production (FVNap). Epigallocatechin-gallate (EGCG) and epicatechin-gallate (ECG) were highly recovered 4- and 125-fold, respectively, by adding FVNap. They were mostly affected by the radical scavenging activity provided from FVNap, showing remarkable 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (10769.3 µg/g) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (8341.5 µg/g) values. The intestinal cellular uptake of epicatechins in GTE increased with the FVNap addition as follows: EGCG (332.46 ± 136.18%) > ECG (273.92 ± 97.92%) > epicatechin (EC) (150.22 ± 12.59%) > epigallocatechin (EGC) (131.21 ± 8.51%). EnzGTE and EnzGTE + FVNa were revealed to have a significant downregulation on the expression of P-glycoprotein (P-gp), up to 0.06- and 0.6-fold, respectively. The gene expression of multidrug resistance associated proteins 2 (MRP2) was reduced in EnzGTE + FVNap. The results suggest that coconsumption GTE or EnzGTE with GTE-derived flavonols could improve the bioavailability of epicatechins.
Asunto(s)
Camellia sinensis/metabolismo , Catequina/análogos & derivados , Flavonoles/metabolismo , Glicósidos/metabolismo , Extractos Vegetales/metabolismo , Disponibilidad Biológica , Biotransformación , Células CACO-2 , Camellia sinensis/química , Catequina/química , Catequina/metabolismo , Flavonoles/química , Glicósidos/química , Humanos , Mucosa Intestinal/metabolismo , Extractos Vegetales/química , Té/químicaRESUMEN
The impacts of onion peel (OP) and Dendropanax morbifera (DM), as excipient foods rich in flavonols, on the digestive recovery, intestinal absorption, and pharmacokinetics of GT epicatechins were studied via an in vitro digestion model system with Caco-2 cells and an in vivo study. The digestive stability of total epicatechins recovered from GT upon the addition of 2% DM was up to 1.12 times higher than that observed with OP. The combined effects of OP and DM, which were observed with 2% OP + DM in a ratio of 1 : 4 (w : w), significantly increased (by a factor of 1.31) the digestive recovery of total epicatechins (p < 0.05). Remarkable cellular uptakes of EC (185.36%) and ECG (188.08%) were found with 4% OP + DM (4 : 1, w : w), and those of EGC (112.30%) and EGCG (136.27%) were obtained with 2% OP + DM (4 : 1, w : w) and 1% OP + DM (1 : 1, w : w), respectively. The peak plasma concentrations of total epicatechins from GT, GT + 5% OP, GT + 5% DM, and GT + 2% OP + 2% DM were 1044.78 ± 609.10, 2267.18 ± 3734.38, 1270.35 ± 547.59, and 714.53 ± 499.27 ng mL-1, respectively. The Cmax value of total epicatechins in rats orally administrated with GT with 5% OP was found to be approximately twice of that obtained with GT alone. The co-ingestion of GT with flavonol-rich excipient foods possibly enhances the absorption of epicatechins because flavonols act as not only enhancers of digestive stability but also modulators of the biotransformation of epicatechins. The results obtained from the current study suggest that the absorption of GT catechins can vary depending upon the kinds and doses of excipient foods co-ingested.
Asunto(s)
Araliaceae/química , Catequina/química , Catequina/farmacocinética , Flavonoides/química , Cebollas/química , Extractos Vegetales/química , Té/química , Animales , Disponibilidad Biológica , Células CACO-2 , Catequina/administración & dosificación , Excipientes/química , Humanos , Masculino , Extractos Vegetales/farmacocinética , Ratas Sprague-DawleyRESUMEN
Annona muricata, commonly known as Graviola, has been utilized as a traditional medicine to treat various human diseases. The aim of this study was to examine the immune-enhancing activity of Graviola leaf extracts in RAW 264.7 macrophage cells. Active ingredients in Graviola leaf extracts (GE) were identified as kaempferol-3-O-rutinoside and quercetin-3-O-rutinoside by LC-MS/MS. When treated with steam or 50% ethanol GE, cell morphology was altered due to initiation of cell differentiation. While the cell viability was not altered by the steam GE, it was reduced by the ethanol GE. Both steam and ethanol GE induced the transcriptional expression of cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß, but only the steam extract upregulated inducible nitric oxide synthase (iNOS). In consistence with mRNA expression, the production of TNF-α and nitrite was elevated by both steam and ethanol extracts of Graviola leaves. This is mainly due to activation of mitogen-activated protein (MAP) kinase signaling pathways. These results suggest that Graviola leaves enhance immunity by activation of the MAP kinase pathways. These bioactive properties of Graviola indicate its potential as a health-promoting ingredient to boost the immune system.
RESUMEN
The aims of this study were to determine bioactive components of Graviola leaf extracts and to examine the radical scavenging capacity, gene expression and transcription factors of antioxidant enzymes. Rutin, kaempferol-rutinoside, and vitamin U were identified from the steaming and 50% EtOH extracts of Graviola leaves. Graviola leaf extracts effectively scavenged peroxy and nitrogen radicals. 50% EtOH of Graviola leaves provided a 1-2.9 times higher trolox equivalent than the steaming extract. It also had a higher VCEAC. Graviola leaf extracts reduced the generation of reactive oxygen species (ROS) induced by H2O2 in a dose-dependent manner. The 50% EtOH extract of Graviola leaves upregulated SOD1 and Nrf2, but catalase and HMOX1 were not altered by the 50% EtOH extract of Graviola leaves.
Asunto(s)
Annona/química , Antioxidantes/metabolismo , Extractos Vegetales/farmacología , Hojas de la Planta/química , Regulación hacia Arriba , Catalasa/genética , Catalasa/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Células Hep G2 , Humanos , Peróxido de Hidrógeno/metabolismo , Quempferoles/análisis , Quempferoles/farmacología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Rutina/análisis , Rutina/farmacología , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vitamina U/análisis , Vitamina U/farmacologíaRESUMEN
Chitooligosaccharide (CO) has been reported to have potential antiobestic effects in a few studies, but the antiobesity properties of CO and its related mechanisms in models of dietary obesity remain unclear. We investigated the effect of CO on body weight gain, size of adipocytes, adipokines, and lipid profiles in high-fat (HF) diet-induced obese mice and on the gene expression in adipose tissue using a complementary DNA microarray approach to test the hypothesis that CO supplementation would alleviate HF diet-induced obesity by the alteration of adipose tissue-specific gene expression. Male C57BL/6N mice were fed a normal diet (control), HF diet, or CO-supplemented HF diet (1% or 3%) for 5 months. Compared with the HF diet mice, mice fed the 3% CO-supplemented diet gained 15% less weight but did not display any change in food and energy intake. Chitooligosaccharide supplementation markedly improved serum and hepatic lipid profiles. Histologic examination showed that epididymal adipocyte size was smaller in mice fed the HF + 3% CO. Microarray analysis showed that dietary CO supplementation modulated adipogenesis-related genes such as matrix metallopeptidases 3, 12, 13, and 14; tissue inhibitor of metalloproteinase 1; and cathepsin k in the adipose tissues. Twenty-five percent of the CO-responsive genes identified are involved in immune responses including the inflammatory response and cytokine production. These results suggest that CO supplementation may help ameliorate HF diet-induced weight gain and improve serum and liver lipid profile abnormalities, which are associated, at least in part, with altered adipose tissue gene expression involved in adipogenesis and inflammation.
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Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Oligosacáridos/uso terapéutico , Adipocitos/metabolismo , Adipocitos/patología , Adipogénesis/genética , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Quitosano/farmacología , Quitosano/uso terapéutico , Citocinas/genética , Citocinas/metabolismo , Grasas de la Dieta/efectos adversos , Suplementos Dietéticos , Ingestión de Energía/efectos de los fármacos , Inflamación/genética , Inflamación/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Análisis por Micromatrices , Obesidad/genética , Obesidad/metabolismo , Oligosacáridos/farmacología , Aumento de Peso/efectos de los fármacos , Aumento de Peso/genéticaRESUMEN
The objective of this study was to investigate the effects of anthocyanin-rich bilberry extract (BE) with highly antioxidative potential against doxorubicin (Dox)-induced toxicity in rat and mouse models. Sprague-Dawley rats treated with Dox (15 mg/kg intraperitoneally) showed marked body weight loss, increased abdominal ascites and serum glutamate oxaloacetate transaminase (GOT) level, serum and cardiac lipid peroxidation, myocardial histopathological damage, and depletion of cardiac glutathione (GSH). Dietary supplementation with 1% BE significantly reduced serum lipid peroxidation and increased cardiac creatine phosphokinase activity and total GSH level compared with the levels in the Dox control rats (P < 0.05). Serum GOT and cardiac lipid peroxide levels did not change significantly after BE treatment. Morphologic examination revealed that Dox-induced myocardial damage was also significantly suppressed in rats fed with the 1% BE diet. Oral administration of 500 mg/kg of BE for 10 days to mice treated with Dox (10 mg/kg) partially restored the Dox-induced changes by increasing red blood cell and bone marrow cell counts, and hemoglobin level. Although the protective effects of BE were insufficient to completely counteract the toxic effects of Dox, these results suggest that BE supplementation provides moderate protection against Dox-induced cardiac and hematopoietic damage.
Asunto(s)
Antocianinas/farmacología , Doxorrubicina/toxicidad , Animales , Corazón/efectos de los fármacos , Peroxidación de Lípido , Masculino , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales , Ratas , Ratas Sprague-Dawley , Vaccinium myrtillusRESUMEN
The neuroprotective effect of six aqueous extracts and one alcoholic extract prepared from seven medicinal plants that have been recorded as having therapeutic effects for stroke in Korean traditional medicine were studied using both in vitro and in vivo cerebral ischemia models. Among the extracts tested, the aqueous extracts of Acorus gramineus, Chrysanthemum indicum, and Pinus densiflora and the alcoholic extract of Vitis vinifera significantly increased the cell viability of SK-N-SH human neuroblastoma cells exposed to oxygen-glucose deprivation (P < .05). Following two-vessel occlusion in gerbils, extracts of P. densiflora and V. vinifera significantly increased the number of surviving cells/mm(2) of the CA1 region by 2.1-2.2-fold (P < .01). Oral or intraperitoneal administration of S-allyl cysteine, as a positive control, also markedly increased cell survival up to about 3.3-fold at the dosage of 300 mg/kg of body weight (P < .01). These results indicate that P. densiflora and V. vinifera exert neuroprotective effects against ischemic insults in both the in vitro and in vivo cerebral ischemia models and prompted us to further characterize the detailed mechanism of action and elucidate the active principles.
Asunto(s)
Fármacos Neuroprotectores/administración & dosificación , Fitoterapia , Extractos Vegetales/administración & dosificación , Plantas Medicinales/química , Accidente Cerebrovascular/tratamiento farmacológico , Acorus/química , Angelica/química , Animales , Isquemia Encefálica/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Chrysanthemum/química , Gerbillinae , Hipocampo/patología , Humanos , Corea (Geográfico) , Masculino , Neuroblastoma , Neuronas/patología , Oxígeno/administración & dosificación , Pinus/química , Accidente Cerebrovascular/patología , Vitis/químicaRESUMEN
The toxicities associated with 5-fluorouracil (5-FU), a potent broad-spectrum chemotherapeutic agent, can not only affect the morbidity and the efficacy of chemotherapy but also limit its clinical use. The objective of this study is to investigate the effects of a commercial anthocyanin-rich extract from bilberry (AREB) against 5-FU-induced myelotoxicity in vivo, and against chemosensitivity to 5-FU in vitro. A single injection of 5-FU at 200 mg/kg induced severe peripheral erythrocytopenia, thrombocytopenia and leucopenia as well as hypocellularity of the spleen and bone marrow in C57BL/6 mice. Oral administration of 500 mg/kg of AREB for 10 days significantly increased the number of red blood cells, neutrophils, and monocytes in peripheral blood to 1.2-fold, 9-fold, and 6-fold, respectively, compared with those seen after treatment with 5-FU alone (p< 0.05-0.001). The hypocellularity of the spleen and bone marrow caused by 5-FU was also distinctly alleviated in the AREB-treated group. Furthermore, AREB treatment with 50 and 100 microg/ml as a monomeric anthocyanin did not interfere with, but rather enhanced the chemotherapeutic efficacy of 5-FU in vitro. These results suggest that AREB may have protective potential against 5-FU-induced myelotoxiciy and/or the ability to enhance the chemotherapeutic effectiveness of 5-FU.
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Antocianinas/farmacología , Fluorouracilo/toxicidad , Vaccinium myrtillus/química , Administración Oral , Animales , Antocianinas/administración & dosificación , Antocianinas/análisis , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Recuento de Células , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Células HT29 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/citología , Monocitos/efectos de los fármacos , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Bazo/citología , Bazo/efectos de los fármacos , Factores de TiempoRESUMEN
The volatile extract from Allii Fistulosi Bulbus (VEAF) was isolated by steam distillation under reduced pressure, followed by continuous liquid-liquid extraction, and its effects on aflatoxin B1 (AFB1)-induced oxidative stress were investigated in human hepatoma cells (HepG2). The main constituents of the VEAF, identified by gas chromatography/mass spectrometry, were 2-octyl-5-methyl-3(2H)-furanone, 2-hexyl-5-methyl-3(2H)-furanone, 2,5-dimethylthiophene, 3,5-diethyl-1,2,4-trithiolane and 3,4-dimethyl-2,5-dihydro-thiophene-2-one. VEAF significantly inhibited the formation of intracellular reactive oxygen species caused by AFB1 in a dose-dependent manner, concomitant with a significant decrease in the AFB1-induced cytotoxicity. VEAF pretreatment significantly reduced the levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation, whereas increased the level of reduced glutathione. The level of 8-hydroxy-2'-deoxyguanosine, a DNA oxidative stress marker, was also decreased by 49-59% with pretreatment of VEAF. With respect to the activity of AFB1 metabolizing enzymes, VEAF significantly increased the activity of glutathione S-transferase, and significantly decreased the cytochrome (CYP) P450 3A4 activity, but had a little effect on the CYP1As. These results suggest that VEAF may be selectively effective in alleviating the AFB1-induced oxidative stress, and lead to cytoprotection against AFB1 exposure.
Asunto(s)
Aflatoxina B1/toxicidad , Allium/química , Carcinoma Hepatocelular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Neoplasias Hepáticas/metabolismo , Estrés Oxidativo/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Peroxidación de Lípido , Neoplasias Hepáticas/tratamiento farmacológico , Extractos Vegetales/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , VolatilizaciónRESUMEN
Volatile extracts were isolated from dried medicinal plants [Angelica tenuissimae roots (AT, Angelica tenuissima Nakai), peppermint leaves (PL, Mentha arvensis L.), pine needles (PN, Pinus sylvestris L.), and sweet flag leaves (SF, Acorus gramineus Rhizoma)] using steam distillation under reduced pressure, followed by continuous liquid-liquid extraction (DRP-LLE). The extracts were then analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The major volatile constituents of AT, PL, PN, and SF were 3-butylidene-4,5-dihydrophthalide (32 mg/g), menthol (18 mg/g), thunbergol (2.1 mg/g), and cis-asarone (37 mg/g), respectively. The inhibitory activity (%) of the extracts against hexanal oxidation ranged from 33 to 98% at a level of 50 microg/mL. Among the volatile extracts, PL and PN increased cell viabilities by 10 and 24%, respectively, at a dose of 1 microg/mL, compared to that of H2O2-treated brain neuroblastoma cells, SK-N-SH. However, a 20% reduction in the malonaldehyde level, an index for lipid peroxidation, was observed at only 1 microg/mL concentration of PN.