Azoxymethane-Induced Colorectal Cancer Mice Treated with a Polyphenol-Rich Apple Extract Show Less Neoplastic Lesions and Signs of Cachexia.
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ABSTRACT:
SUBMITTER: Marzo F
PROVIDER: S-EPMC8071383 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fruits such as apples are a dietary source of polyphenols and have health benefits. We studied the benefits of apple polyphenols in reducing intestinal infections. We explored the potential roles of apple polyphenols in combating Clostridioides difficile-induced intestinal infections by modulating the intestinal microbiota and metabolism in our study. Mice fed with apple polyphenols exhibited higher survival rates and improved diarrhea symptoms in a C. difficile infection mouse model given once-daily apple polyphenol extract (200 or 400 mg/kg bw) or phosphate-buffered saline. Feeding polyphenols enhanced anti-inflammatory effects and colon barrier integrity. In addition, apple polyphenols mitigated intestinal microbiota disorders in C. difficile infection, modulating the intestinal microbiota and increasing the abundance of beneficial microbiota. Apple polyphenols also improved fecal metabolic alterations in C. difficile-infected mice and modulated the expression of pathways related to intestinal inflammation. Our results suggest that apple polyphenol extract is a potential prebiotic agent that affects the intestinal microbiota and metabolism, thereby positively influencing intestinal infections.
| S-EPMC9694464 | biostudies-literature
Project description:The aim of the current study was to evaluate the effect of apple peel polyphenol extract (APPE) on the physicochemical and microbiological properties of probiotic yoghurt. Five concentrations of APPE were added in probiotic yoghurt as: (1) CTL, control without APPE; (2) AE1, addition of 1% APPE; (3) AE2, addition of 2% APPE; (4) AE3, addition of 3% APPE; (5) AE4, addition of 4% APPE; and (6) AE5, addition of 5% APPE. The prepared probiotic yoghurt was stored at 4 °C for 21 days and analyzed for physicochemical and microbiological properties. The initial viable count of L. bulgaricus, S. thermophilus, B. lactis and L. acidophilus were similar in all yoghurt samples at day 1. The maximum viability loss of probiotics was observed in CTL (p < 0.05). The lowest viability loss of probiotics was observed in AE5 samples (p < 0.05). The acidity, water holding capacity and viscosity were increased with the addition of APPE. No significant effects were observed on milk fat and total solid contents of probiotic yoghurt with the addition of APPE. The total phenolic contents of probiotic yoghurt increased significantly as 0.59, 0.71, 0.97, 1.18, 1.35 in AE1, AE2, AE3, AE4 and AE5, samples respectively. It was observed that AE3 and AE4 samples had better taste, flavour and colour with good texture. The survival of probiotics and antioxidant activity of the yoghurts were enhanced with the addition of APPE. In conclusion, apple peels could be successfully used as prebiotic in yoghurt with increased viable counts of probiotics.
| S-EPMC7020425 | biostudies-literature
Project description:In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders-in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging.
| S-EPMC7828649 | biostudies-literature
Project description:Inflammatory bowel conditions can involve nearly all organ systems and induce pathological processes through increased oxidative stress, lipid peroxidation and disruption of the immune response. Patients with inflammatory bowel disease (IBD) are at high risk of having extra-intestinal manifestations, for example, in the hepatobiliary system. In 30% of patients with IBD, the blood values of liver enzymes, such as AST and ALT, are increased. Moreover, treatments for inflammatory bowel diseases may cause liver toxicity. Apple polyphenol extracts are widely acknowledged for their potential antioxidant effects, which help prevent damage from oxidative stress, reduce inflammation, provide protection to the liver, and enhance lipid metabolism. The aim of this study was to investigate whether the polyphenol apple extract from Malus domestica cv. 'Limoncella' (LAPE) may be an effective intervention for the treatment of IBD-induced hepatotoxicity. The LAPE was administrated in vivo by oral gavage (3-300 mg/kg) once a day for 3 consecutive days, starting 24 h after the induction of dinitro-benzenesulfonic acid (DNBS) colitis in mice. The results showed that LAPE significantly attenuated histological bowel injury, myeloperoxidase activity, tumor necrosis factor and interleukin (IL-1β) expressions. Furthermore, LAPE significantly improved the serum lipid peroxidation and liver injury in DNBS-induced colitis, as well as reduced the nuclear transcription factor-kappaB activation. In conclusion, these results suggest that LAPE, through its antioxidant and anti-inflammatory properties, could prevent liver damage induced by inflammatory bowel disease.
| S-EPMC10969867 | biostudies-literature
Project description:γδ T cells are lymphocytes that function in both innate and adaptive immune responses, and our laboratory has previously reported that both bovine and human γδ T cells are primed for secondary responses by tannin components of the unripe apple peel (APP). In this report we began to investigate the mechanism by which priming occurs. We performed a microarray analysis on sorted bovine γδ T cells treated with APP and observed significant increases in transcripts encoding select inflammatory cytokines, such as GM-CSF, IL-8, and IL-17, but not markers of TCR stimulation such as IFNγ. When injected into the gut of mice, APP induced a robust influx of neutrophils into both the blood and peritoneum as measured by FACS. Importantly, both GM-CSF and IL-8 proteins were detected in these animals. Further studies were performed using the human γδ T cell-line MOLT-14, as large numbers of cells were required for subsequent experiments. Using these cells we found that both the GM-CSF and IL-8 mRNAs were significantly upregulated and stabilized in cells treated with APP. Finally, we show that the ERK1/2 MAPK pathway was activated in APP-treated MOLT-14 cells, and that this pathway plays a role in the mRNA stabilization we observed. Together, our data describe a unique inflammatory response in bovine, murine, and human γδ T cells in response to APP, and suggest that mRNA stability mechanisms could account for the priming phenotype we previously observed.APP has a distinctive gamma delta T cells specific priming activity. Keywords: comparison of 2 treatment types, tannin, gamma delta T cells
2010-08-10 | GSE13321 | GEO
Project description:The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 ?mol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.
| S-EPMC3793841 | biostudies-literature
Project description:BackgroundAlzheimer's disease (AD) and Parkinson's disease (PD) are multifactorial neurodegenerative disorders that are mostly treated with drugs inhibiting key enzymes of cholinergic and aminergic neurotransmission, such as acetyl and butyryl cholinesterase (AChE, BuChE) or monoamine oxidases (MAO)-A/B, and of Aβ1-40 aggregation. Diet plant components with multitarget functions are promising compounds in the prevention of AD and PD. Our aim was to identify neuroprotective compounds from Annurca apple polyphenol extract (AFPE).MethodsAFPE was fractionated by gel filtration, and the eluted peaks were subjected to chemical analyses (i.e., RP-HPLC and mass spectrometry), determination of inhibitory enzyme activity and cell effects by MTT, and morphology assays.ResultsIn AFPE, we identified thaumatin-like protein 1a, belonging to the pathogenesis-related protein (PR) family. This protein showed the best inhibitory activity on AChE, MAO-A (IC50 = 5.53 µM and 1.71 µM, respectively), and Aβ1-40 fibril aggregation (IC50 = 9.16 µM), compared to AFPE and other polyphenol-containing fractions. Among the latter, Peak 4 reverted Aβ fibril formation (IC50 = 104.87 µM). Moreover, thaumatin-like protein 1a protected AGS and MKN-28 cells from serum-deprivation-induced stress conditions.ConclusionsWe showed that AFPE exerted neuroprotective functions not only through its polyphenols but also through thaumatin-like protein 1a, which acted like a multitarget molecule.
| S-EPMC10821328 | biostudies-literature
Project description:γδ T cells are lymphocytes that function in both innate and adaptive immune responses, and our laboratory has previously reported that both bovine and human γδ T cells are primed for secondary responses by tannin components of the unripe apple peel (APP). In this report we began to investigate the mechanism by which priming occurs. We performed a microarray analysis on sorted bovine γδ T cells treated with APP and observed significant increases in transcripts encoding select inflammatory cytokines, such as GM-CSF, IL-8, and IL-17, but not markers of TCR stimulation such as IFNγ. When injected into the gut of mice, APP induced a robust influx of neutrophils into both the blood and peritoneum as measured by FACS. Importantly, both GM-CSF and IL-8 proteins were detected in these animals. Further studies were performed using the human γδ T cell-line MOLT-14, as large numbers of cells were required for subsequent experiments. Using these cells we found that both the GM-CSF and IL-8 mRNAs were significantly upregulated and stabilized in cells treated with APP. Finally, we show that the ERK1/2 MAPK pathway was activated in APP-treated MOLT-14 cells, and that this pathway plays a role in the mRNA stabilization we observed. Together, our data describe a unique inflammatory response in bovine, murine, and human γδ T cells in response to APP, and suggest that mRNA stability mechanisms could account for the priming phenotype we previously observed.APP has a distinctive gamma delta T cells specific priming activity. Keywords: comparison of 2 treatment types, tannin, gamma delta T cells To begin to understand the effects of APP in innate immunity, we investigated the global gene expression profiles of stimulated bovine gamma delta T cells. Peripheral blood from 2 neonatal bovine calves was collected. gamma delta T cells were sorted to >97% purity using a FACS Vantage. Cells were placed in culture and stimulated with either an aqueous extract of APP (42.2ug/ml) or PBS for 4 hours after which RNA was extracted and processed for microarray analysis following standard protocols from Affymetrix.
2010-08-10 | E-GEOD-13321 | biostudies-arrayexpress
Project description:Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system.
| S-EPMC3742268 | biostudies-literature
Project description:ScopeBacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. This study examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases.Methods and resultsThe expression of mucus constituent mucin 5AC (MUC5AC) in FVB/NJ mice and NCI-H292 epithelial cells is analyzed. Nontypeable Haemophilus influenzae (NTHi)-infected mice developed increased MUC5AC mRNA, which a diet containing phloretin inhibited. In NCI-H292 cells, NTHi, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa increased MUC5AC mRNA, which phloretin inhibited. Phloretin also diminished NTHi-induced MUC5AC protein secretion. NTHi-induced increased MUC5AC required toll-like receptor 4 (TLR4) and NADH oxidase 4 (NOX4) signaling and subsequent activation of the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Phloretin inhibited NTHi-induced TLR4/NOX4 and EGFR/MAPK signaling, thereby preventing increased MUC5AC mRNA. EGFR activation can also result from increased EGFR ligand synthesis and subsequent ligand activation by matrix metalloproteinases (MMPs). In NCI-H292 cells, NTHi increased EGFR ligand and MMP1 and MMP13 mRNA, which phloretin inhibited.ConclusionsIn summary, phloretin is a promising therapeutic candidate for preventing bacterial-induced mucus overproduction.
| S-EPMC8163070 | biostudies-literature