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Natural product is an excellent candidate for alternative medicine for disease management. The bulb of E. bulbosa is one of the notable Iridaceae family with a variety therapeutic potential that is widely cultivated in Southeast Asia. The bulb has been used traditionally among the Dayak community as a folk medicine to treat several diseases like diabetes, breast cancer, nasal congestion, and fertility problems. The bulb is exceptionally rich in phytochemicals like phenolic and flavonoid derivatives, naphthalene, anthraquinone, and naphthoquinone. The electronic database was searched using various keywords, i.e., E. bulbosa, E. americana, E. palmifolia, E. platifolia, and others due to the interchangeably used scientific names of different countries. Scientific investigations revealed that various pharmacological activities were recorded from the bulb of E. bulbosa including anti-cancer, anti-diabetic, anti-bacterial, anti-fungi, anti-viral, anti-inflammatory, dermatological problems, anti-oxidant, and anti-fertility. The potential application of the bulb in the food industry and in animal nutrition was also discussed to demonstrate its great versatility. This is a compact study and is the first study to review the extensive pharmacological activities of the E. bulbosa bulb and its potential applications. The development of innovative food and pharma products from the bulb of E. bulbosa is of great interest.
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Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Iridaceae/química , Extractos Vegetales/farmacología , Animales , HumanosRESUMEN
BACKGROUND: The development of insulin resistance is multifactorial, with maternal pre- and postnatal nutrition having significant influences. In this regard, high fat diet (HFD) feeding in pregnancy has been shown to increase risks of metabolic diseases. Thus, we investigated the effects of supplementation of HFD with germinated brown rice (GBR) and GBR-derived gamma oryzanol-rich extract (OE) on insulin resistance and its epigenetic implications in pregnant rats and their offsprings. METHODS: Pregnant female Sprague dawley rats were fed with HFD alone, HFD + GBR or HFD + OE (100 or 200 mg/kg/day) throughout pregnancy and lactation. Their offsprings were weaned at 4 weeks post-delivery and were followed up until 8 weeks. Serum levels of adipokines were measured in dams and their offsprings, and global DNA methylation and histone acetylation patterns were estimated from the liver. RESULTS: The dams and offsprings of the GBR and OE groups had lower weight gain, glycemic response, 8-Iso prostaglandin, retinol binding protein 4 and fasting insulin, and elevated adiponectin levels compared with the HFD group. Fasting leptin levels were lower only in the GBR groups. Hepatic global DNA methylation was lower in the GBR groups while hepatic H4 acetylation was lower in both GBR and OE dams. In the offsprings, DNA methylation and H4 acetylation were only lower in the OE group. However, dams and offsprings of the GBR and OE groups had higher hepatic H3 acetylation. CONCLUSIONS: GBR and OE can be used as functional ingredients for the amelioration of HFD-induced epigeneticallymediated insulin resistance.
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Dieta Alta en Grasa , Resistencia a la Insulina , Oryza , Preparaciones de Plantas/farmacología , Efectos Tardíos de la Exposición Prenatal , Acetilación , Adiponectina/sangre , Animales , Peso Corporal/efectos de los fármacos , Metilación de ADN , Femenino , Germinación , Histonas/metabolismo , Leptina/sangre , Extractos Vegetales/farmacología , Embarazo , Ratas , Ratas Sprague-Dawley , Proteínas Plasmáticas de Unión al Retinol/metabolismoRESUMEN
Cocoa polyphenol (CP), due to their biological actions, may be supplementary treatments for adipose tissue-fat gain. However, the molecular mechanism of CPs is still ambiguous. This study investigated the hypothesis that CP treatment modulates expressing of lipid metabolism genes in mesenteric white adipose tissue (MES-WAT). Sprague-Dawley (SD) rats were fed a low-fat (LF) or high-fat (HF) diet for 12 weeks. Thereafter, HFD rats (n = 10/group) were treated at a dose of 600 mg/kg bw/day CPs (HFD + CPs) for 4 weeks. DNA microarray analysis resulted in 753 genes of the 13,008 genes expressed. Bioinformatics tools showed CP treatment significantly decreased gene expression levels for lipogenic enzymes, while increased the mRNA levels responsible for lipolysis enzymes. CP administration differentially regulates gene expression involved in lipid metabolism in MES-WAT. These data unveil a new insight into the molecular mechanisms underlying the pharmacological effect of CPs on obesity biomarkers in obese rats.
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Cacao/química , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/genética , Polifenoles/administración & dosificación , Tejido Adiposo Blanco/metabolismo , Animales , Dieta con Restricción de Grasas , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Humanos , Masculino , Obesidad/etiología , Análisis de Secuencia por Matrices de Oligonucleótidos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Polifenoles/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.
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Acetatos/química , Regulación hacia Abajo/efectos de los fármacos , Lipopolisacáridos/toxicidad , Moringa oleifera/química , FN-kappa B/metabolismo , Extractos Vegetales , Transducción de Señal/efectos de los fármacos , Animales , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
The antioxidant components of cocoa powder, which is rich in polyphenols, were isolated using column chromatography and high performance liquid chromatography. Polyphenolic compounds were then characterized by high-performance liquid chromatography/Ultraviolet and electronspray ionization-tandem mass spectrometry (HPLC-UV-/ESI-MS-MS). As a result, five phenolic compounds were detected. In this study we also investigated scavenging or the total antioxidant capacity (%) of cocoa polyphenol (CP) fractionated from cocoa powder extract. 114.0 mg/g of gallic acid -equivalent phenolics and 94.3 mg/g catechin- equivalent flavonoids were quantified in this extract. Their free radical-scavenging activity was assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay, ß-carotene bleaching test, and xanthine oxidase inhibitory activity (OX). Total antioxidant capacity (TAC) was further assessed against the myoglobin-induced oxidation of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (ABTS) and expressed as Trolox equivalent. A high correlation between TAC and phenolic contents indicated that phenolic compounds from cocoa were a major contributor of antioxidant activity (0.967 ≤ r ≤ 1.00). CP extract had significantly (P < 0.05) potential antioxidant activities with various concentrations. These results suggest that Polyphenols-rich cocoa extract possess prominent medical properties and can be exploited as natural drug to treat free radical associated diseases.
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BACKGROUND & OBJECTIVES: Enhanced muscle strength is seen when resistance exercise is combined with the consumption of nutritional supplements. Although there is a limited number of studies available about the efficacy of gamma oryzanol supplementation with resistance exercise in humans, but its usage as a nutritional supplement for strength is common in athletes. The aim of this study was to determine the effects of gamma oryzanol supplementation during 9-week resistance training on muscular strength and anthropometric measurements of young healthy males. METHODS: In this double-blind clinical trial, changes of anthropometric measurements and muscular strength were studied after chronic resistance exercise and gamma oryzanol supplementation in 30 healthy volunteers (16 in supplement and 14 in placebo). Each day, gamma oryzanol supplement (600 mg) and placebo (the same amount of lactose) were consumed after training. The participants exercised with 80 per cent 1-Repetition Maximum (1-RM), for one hour and four days/week. Anthropometric measurements and subjects' 1-RM for muscular strength were determined at the commencement and end of the 9-week study. RESULTS: There was no significant difference between the baseline characteristics and target variables at baseline between the two groups. After gamma oryzanol supplementation, there was no significant difference in the means of anthropometric and skin fold measurements between the supplement and placebo groups. However, there were significant differences between the supplement and placebo groups for 1-RM of bench press and leg curl, which showed that gamma oryzanol improved muscle strength following resistance training. INTERPRETATION & CONCLUSIONS: Our findings indicated that 600 mg/day gamma oryzanol supplementation during the 9-week resistance training did not change anthropometric and body measurements, but it increased muscular strength in young healthy males. Further, studies need to be done in trained athletes, women, and in patients who suffer from muscular fatigue.
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Suplementos Dietéticos , Fuerza Muscular/efectos de los fármacos , Fenilpropionatos/farmacología , Entrenamiento de Fuerza/estadística & datos numéricos , Adulto , Antropometría , Pesos y Medidas Corporales , Humanos , Irán , MasculinoRESUMEN
BACKGROUND: Brewers' rice is locally known as temukut, is a byproduct of the rice milling process, and consists of broken rice, rice bran, and rice germ. Unlike rice bran, the health benefit of brewers' rice has yet to be fully studied. Our present study aimed to identify the chemopreventive potential of brewers' rice with colonic tumor formation and to examine further the mechanistic action of brewers' rice during colon carcinogenesis. METHODS: Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) azoxymethane (AOM) alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. Rats in group 2 to 5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. Colon tumor incidence and multiplicity was assessed by hematoxylin and eosin (H&E) staining. The expression of ß-catenin, cyclooxygenase-2 (COX-2), and Ki-67 was evaluated by immunohistochemical staining. The apoptosis-inducing activity was analyzed using a TUNEL assay. The data were analyzed using a one-way analysis of variance (ANOVA) with P-value<0.05 was considered significant. RESULTS: Overall analyses revealed that brewers' rice reduced colon tumor incidence and multiplicity. The results from immunohistochemistry analysis also showed that brewers' rice decreased the expression of ß-catenin, COX-2, and Ki-67 in a dose-dependent manner. Furthermore, TUNEL analysis demonstrated that administration of brewers' rice in AOM-induced rat colorectal cancer resulted in a dose-dependent increase in cell apoptosis. CONCLUSIONS: Taken together, our data suggested that brewers' rice can inhibit cell proliferation, induce apoptosis, and suppress COX-2 and ß-catenin expression via the Wnt signaling pathway and holds great promise in the field of chemoprevention as a dietary agent.
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Apoptosis/efectos de los fármacos , Azoximetano/administración & dosificación , Azoximetano/efectos adversos , Neoplasias del Colon/dietoterapia , Oryza/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Animales , Carcinogénesis , Proliferación Celular , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Neoplasias del Colon/fisiopatología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Masculino , Oryza/química , Ratas , Ratas Sprague-Dawley , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Inositol hexaphosphate (IP6), or phytic acid is a natural dietary ingredient and has been described as a "natural cancer fighter", being an essential component of nutritional diets. The marked anti-cancer effect of IP6 has resulted in our quest for an understanding of its mechanism of action. In particular, our data provided strong evidence for the induction of apoptotic cell death, which may be attributable to the up-regulation of Bax and down-regulation of Bcl-xl in favor of apoptosis. In addition, the up-regulation of caspase-3 and -8 expression and activation of both caspases may also contribute to the apoptotic cell death of human colorectal adenocarcinoma HT-29 cells when exposed to IP6. Collectively, this present study has shown that rice bran IP6 induces apoptosis, by regulating the pro- and anti-apoptotic markers; Bax and Bcl-xl and via the activation of caspase molecules (caspase-3 and -8).
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Antineoplásicos Fitogénicos/química , Oryza/química , Ácido Fítico/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 8/genética , Caspasa 8/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células HT29 , Humanos , Oryza/metabolismo , Ácido Fítico/aislamiento & purificación , Ácido Fítico/farmacología , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
Diabetes is associated with an imbalance between oxidants and antioxidants, leading to oxidative stress. This imbalance contributes to the development and progression of diabetic complications. Similarly, renal and liver diseases are characterised by oxidative stress, where an excess of oxidants overwhelms the antioxidant defense mechanisms, causing tissue damage and dysfunction. Restoring the oxidant-antioxidant balance is essential for mitigating oxidative stress-related damage under these conditions. In this current study, the efficacy of stingless bee honey (SBH) and its phenolic-rich extract (PRE) in controlling the oxidant-antioxidant balance in high-fat diet- and streptozotocin/nicotinamide-induced diabetic rats was investigated. The administration of SBH and PRE improved systemic antioxidant defense and oxidative stress-related measures without compromising liver and renal functioning. Analyses of the liver, skeletal muscle and adipose tissues revealed differences in their capacities to scavenge free radicals and halt lipid peroxidation. Transcriptional alterations hypothesised tissue-specific control of KEAP1-NRF2 signalling by upregulation of Nrf2, Ho1 and Sod1 in a tissue-specific manner. In addition, hepatic translational studies demonstrated the stimulation of downstream antioxidant-related protein with upregulated expression of SOD-1 and HOD-1 protein. Overall, the results indicated that PRE and SBH can be exploited to restore the oxidant-antioxidant imbalance generated by diabetes via regulating the KEAP1-NRF2 signalling pathway.
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Diabetes Mellitus Experimental , Miel , Abejas , Ratas , Animales , Antioxidantes/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Oxidantes , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo , Fenoles/farmacologíaRESUMEN
Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and anti-inflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD.
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Ulcerative colitis (UC) is a serious health condition and defined as inflammation in the colon. Untreated, UC can develop into colitis-associated cancer (CAC), for which effective medicines are not available. Natural products are a better choice to treat UC by alleviating the inflammation. Caffeic acid phenethyl ester (CAPE) is a phenolic compound and known for its beneficial effects, including antibacterial, anti-inflammatory, anti-diabetic, and anticancer. We aimed to study the effect of CAPE on dextran sulfate sodium (DSS)-induced UC in mouse model. Administration of CAPE to DSS-induced mice protected against colon damage by improving body weight of mice, reducing the weight of spleen, and increased colon length. In addition, administration of CAPE resulted reduced the activity of myeloperoxidase (MPO) and CD68+ positive cells. Furthermore, a significant decrease in the production of key cytokines and the expression of nuclear factor (p65-NF)-κB. Moreover, p65-NF-κB activation was reduced in lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells from mouse origin. CAPE treatment leads to the reduced expressions of intercellular adhesion molecules (ICAM)-1 and vascular cell adhesion molecules (VCAM), both are key cell adhesion molecules. The results of this study clearly indicate that CAPE can potentially control inflammation in the colon and can be used as a therapy for UC.
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FN-kappa BRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The bulb of Eleutherine bulbosa (Mill.) Urb. is an indigenous medicinal plant traditionally used among Dayak people for the management of diabetes, breast cancer, hypertension, stroke, and fertility problems in women. The bulb has been reported with a potent cytotoxic potential but with limited underlying mechanisms. AIM OF THE STUDY: This study aimed to investigate the cytotoxic properties of E. bulbosa ethanolic bulb extracted under optimised extraction condition on retinoblastoma cancer cells (WERI-Rb-1) through in vitro cell culture bioassays. The optimised extraction condition has been determined in the previous reports. MATERIALS AND METHODS: Cytotoxic assay was analysed through MTT assay. Comparison between non-optimised and optimised extraction condition from E. bulbosa ethanolic bulb extract was evaluated. Morphological assessment of apoptotic cells was conducted through acridine orange propidium iodide (AOPI) staining using fluorescence microscopy. Apoptosis assay was carried out through Annexin V-FITC and cell cycle analysis through PI staining. The effect of varying concentrations (IC25, IC50, IC75) of the optimised E. bulbosa ethanolic bulb extract was observed. The mRNA expression was also conducted to confirm the underlying mechanism. RESULTS: The optimised E. bulbosa ethanolic bulb extract markedly suppressed the proliferation of retinoblastoma cancer cells significantly with an IC50 value of 15.7 µg/mL as compared to non-optimised extract (p < 0.01). Fluorescence microscopy revealed that retinoblastoma cancer cells manifested early features of apoptosis-like membrane blebbing, chromatin condensation and formation of apoptotic bodies in a dose-dependent manner. The number of apoptotic cells were greatly observed in early and late apoptosis through Annexin V-FITC and the extract also induced cell arrestment as compared to the untreated group. The apoptosis was confirmed with the upregulation of Bax, Bad, p53, Caspase 3, Caspase 8, and Caspase 9 genes meanwhile, Bcl-2, BcL-xL, Nrf-2, and HO-1 genes were downregulated. CONCLUSION: The optimised E. bulbosa ethanolic bulb extract induced a significant cell death and cell cycle arrestment on retinoblastoma cancer cells. It could be suggested that the induction of apoptosis in retinoblastoma cancer cells may be due to the synergistic effect of the bioactive compounds extracted under optimised extraction condition. Our findings indicated that E. bulbosa bulb could be promising chemotherapeutic potential to treat retinoblastoma cancer cells.
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Apoptosis/efectos de los fármacos , Iridaceae/química , Fitoterapia , Extractos Vegetales/farmacología , Raíces de Plantas/química , Retinoblastoma/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Extractos Vegetales/químicaRESUMEN
Nigella sativa or Black seed (N. sativa L.) is traditionally used for several ailments in many Middle Eastern countries. It is an annual herbaceous plant that belongs to the Ranuculacea family with many beneficial properties as antitumor, antidiabetic, antihypertensive, antioxidative and antibacterial. This work attempted to study the effect of N. sativa seeds powder and oil on atherosclerosis in diet-induced hypercholesterolemic (HC) rabbits in comparison with simvastatin (ST). Twenty-five adult New Zealand male white rabbits, weighing 1.5-2.5 kg, were divided into five groups; normal group (NC, n = 5) and four hypercholesterolemic groups (n = 20): a positive control (PC) and three HC groups force fed diet supplemented with 1000 mg Kg(-1) body weight of N. sativa powder (NSP), 500 mg Kg(-1) body N. sativa oil (NSO) and 10 mg Kg(-1) ST for 8 weeks. Feeding HC rabbits with N. sativa either in powder or oil forms was shown to significantly reduce (P < .05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and enhance high-density lipoprotein cholesterol (HDL) levels after treatment for 2, 4, 6 and 8 weeks compared to the PC group. Plaque formation was significantly inhibited while the intima: media ratio was significantly reduced in the NSP and NSO supplemented groups compared to the PC group. In conclusion, treatment of HC rabbits with N. sativa seeds powder or oil showed hypocholesterolemic and antiatherogenic cardioprotective properties.
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Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p < 0.05) increased T cells (CD4 and CD8) and B cells (CD19) in spleen tissues. The CD335 (natural killer cells) were increased in the CRC-induced mice and limonin treatment restored them to normal levels suggesting reinstatement to normal colon conditions. Limonin apparently mitigated CRC development, by ameliorating adaptive immune responses (CD8, CD4, and CD19), reducing inflammation (serum prostaglandin E2; TNF-α, innate immune responses) and oxidative stress, and enhancing the endogenous anti-oxidation defense reactions (GSH) in CRC-induced mice.
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Adenocarcinoma/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Limoninas/farmacología , Adenocarcinoma/patología , Animales , Antioxidantes/metabolismo , Azoximetano , Neoplasias Colorrectales/patología , Sulfato de Dextran , Modelos Animales de Enfermedad , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacosRESUMEN
[This corrects the article DOI: 10.1155/2018/3142073.].
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INTRODUCTION: Colorectal cancer (CRC) is common, with a worldwide incidence estimated at more than 1 million cases annually. Therefore, the search for agents for CRC treatment is highly warranted. Inositol-6 phosphate (IP6) is enriched in rice bran and possesses many beneficial effects. In the present study the effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 colon cancer cells was studied. MATERIAL AND METHODS: Autophagy was assessed by acridine orange (AO) staining, transmission electron microscopy, and western blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. RESULTS: Incubation of cells with IP6 resulted in downregulation of the p-Akt at 3h. Along with that confocal microscopic analysis of p-AKT, IP6 administration resulted that a diminished expression of p-Akt. mTOR pathway regulates autophagy and incubation with IP6 to HT-29 cells showed decreased expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 phosphate (10 µg/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO staining and transmission electron microscopy. We also found increased expression of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP6. Furthermore, IP6 induced apoptosis, as revealed by annexin V staining. CONCLUSIONS: Our results clearly indicate that IP6 induces autophagy by inhibiting the Akt/mTOR pathway.
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Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1ß, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.
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Amaranthaceae/inmunología , Antiinflamatorios/farmacología , Macrófagos/inmunología , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Animales , Citocinas/metabolismo , Dinoprostona/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/inmunología , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/metabolismo , Tallos de la Planta , Células RAW 264.7 , Transducción de SeñalRESUMEN
Colorectal cancer (CRC) is ranked as the fourth most lethal and commonly diagnosed cancer in the world according to the National Cancer Institute's latest report. Treatment methods for CRC are constantly being studied for advancement, which leads for more clinically effective cancer curing strategy. Patients with prolonged chronic inflammation caused by ulcerative colitis or similar inflammatory bowel disease are known to have high risks of developing CRC. But at a molecular level, oxidative stress due to reactive oxygen species (ROS) is an important trigger for cancer. Hence, in recent years, exogenous antioxidants have been immensely experimented in pre-clinical and clinical trials, considering it as a potential cure for CRC. Significantly, potential antioxidant compounds especially derivatives of medicinal plants have received great attention in the current research trend for CRC treatment. Though antioxidant compounds seem to have beneficial properties for the treatment of CRC, there are also limitations for pure compounds to be tested clinically. Therefore, this review aims to delineate the pharmacological awareness among researchers on using antioxidant compounds to treat CRC and the measures taken to prove the effectiveness of such compounds as impending drug candidates for CRC treatment in modern medication.
Asunto(s)
Antioxidantes/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/farmacología , Enfermedad Crónica , Neoplasias Colorrectales/patología , Humanos , Inflamación/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Especies Reactivas de Oxígeno/metabolismo , Factores de RiesgoRESUMEN
BACKGROUND: The phytoconstituents phytic acid and 4-hydroxyisoleucine have been reported to posses various biological properties. OBJECTIVE: This prompted us to carry out the docking study on these two ligands (phytic acid & 4-hydroxyisoleucine) against eleven targeted enzymes. MATERIALS AND METHODS: Phytic acid & 4-hydroxyisoleucine were evaluated on the docking behaviour of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), tyrosinase, human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), xanthine oxidase (XO), squalene synthase (SQS), nitric oxide synthase (NOS), human aldose reductase (HAR) and lipoxygenase (LOX) using Discovery Studio Version 3.1 (except for LOX, where Autodock 4.2 tool was used). RESULTS: Docking and binding free energy analysis revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase and HNE. Interestingly, we found that 4-hydroxyisoleucine has the potential to dock and bind with all of the eleven targeted enzymes. CONCLUSION: This present study has paved a new insight in understanding 4-hydroxyisoleucine as potential inhibitor against COX-2, mPGES-2, tyrosinase, HNE, MMP 2, MMP 9, XO, SQS, NOS, HAR and LOX. SUMMARY: 4-hydroxyisoleucine has the potential to dock and bind with all 11targeted enzymes such as (cyclooxygenase-2 [COX-2], microsomal prostaglandin E synthase-2 [mPGES-2], tyrosinase, human neutrophil elastase [HNE], matrix metalloproteinase [MMP-2 and -9], xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase)Moreover, docking studies and binding free energy calculations revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase, and HNE; however, for other six target enzymes, it fails to dock. Abbreviations used: COX-2: Cyclooxygenase-2, mPGES-2: Microsomal prostaglandin E synthase-2, HNE: Human neutrophil elastase, MMP-2 and -9: Matrix metalloproteinase-2 and -9, XO: Xanthine oxidase, SQS: Squalene synthase, NOS: Nitric oxide synthase, HAR: Human aldose reductase, LOX: Lipoxygenase, ADME: Absorption, distribution, metabolism, and excretion, TOPKAT: Toxicity Prediction by Computer-assisted Technology.
RESUMEN
The growth and lectin production of Ganoderma applanatum, a white rot fungus, was optimized in broth cultures. The fungus was found to have a higher growth rate and higher lectin activity when grown in a medium adjusted to pH 6.5 at 26°C under stationary conditions. Expression of lectin activity started in 5-day-old mycelial culture; maximum activity was expressed after the 15th day of incubation. Among the various carbon and nitrogen sources tested, the carbon source sucrose and the nitrogen source yeast extract support maximum growth and lectin production. Lectin from G. applanatum was purified by ammonium sulfate precipitation and ion exchange chromatography. The purified fraction revealed a single band with a molecular weight of 35.0 kDa. Moreover, carbohydrates such as mannitol, glucose, sucrose, maltose, mannose, galactose, sorbose, and fructose were found to inhibit the hemagglutinating activity of the lectin. The purified lectins from G. applanatum contain cytotoxic and proapoptotic activities against HT-29 colon adenocarcinoma cells.