|
1
|
Mulinari Turin de Oliveira N, Schiebel CS, Sauruk da Silva K, de Mello Braga LLV, Bach C, Maria-Ferreira D. Efficacy of Dietary Supplementation in the Relief of Inflammatory Bowel Disease: A Systematic Review of Animal Studies. Nutr Rev 2025:nuae224. [PMID: 39992299 DOI: 10.1093/nutrit/nuae224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025] Open
Abstract
CONTEXT Supplementation with dietary components is a promising approach for the treatment of inflammatory bowel disease (IBD). OBJECTIVE The aim was to examine the effects of dietary supplements on experimental animal models of IBD. DATA SOURCES Articles were selected from 2016 to 2021 and from specific databases (PubMed, Embase, and Scopus). DATA EXTRACTION Forty-nine studies were analyzed. DATA ANALYSIS Of the 49 studies, 8 investigated supplementation with oils/polyunsaturated fatty acids, 5 with flavones, 5 with prebiotics and probiotics, 6 with amino acids, 4 with fruits, 4 with vegetables, 2 with minerals, 2 with vitamins, 3 with plants, 2 with polyphenols, and 8 from various sources. Polyunsaturated fatty acids, flavones, prebiotics, and probiotics are among the most extensively studied compounds. Protection is associated with reducing inflammation and oxidative stress, protecting the epithelial barrier and altering the microbiota; however, more rigorous protocols are needed to definitively confirm their protective effects and enable translational research. Fruits, vegetables, plant compounds, minerals, vitamins, and polyphenols, on the other hand, should be studied further and deserve more attention in research. CONCLUSION The results included here support further research into the beneficial effects of supplementation in IBD. Some studies are more advanced and have presented more elaborate protocols, while others still require an increase in knowledge. The identification of dietary supplements that can improve the course of IBD could have an important and lasting impact on the treatment of IBD. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42022295260.
Collapse
Affiliation(s)
- Natalia Mulinari Turin de Oliveira
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| | - Carolina Silva Schiebel
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| | - Karien Sauruk da Silva
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| | - Lara Luisa Valerio de Mello Braga
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| | - Camila Bach
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| | - Daniele Maria-Ferreira
- Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR 80250-060, Brazil
- Faculdades Pequeno Príncipe, Programa de Pós-graduação em Biotecnologia Aplicada à Saúde da Criança e do Adolescente, Curitiba, PR 80250-060, Brazil
| |
Collapse
|
|
2
|
Zhong H, Luo X, Abdullah, Liu X, Hussain M, Guan R. Nano-targeted delivery system: a promising strategy of anthocyanin encapsulation for treating intestinal inflammation. Crit Rev Food Sci Nutr 2025:1-22. [PMID: 39919822 DOI: 10.1080/10408398.2025.2458741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Abstract
Anthocyanins are natural flavonoids derived from plants, widely recognized for their health-promoting effects, specifically to treat inflammatory bowel disease (Crohn's disease and ulcerative colitis). However, certain limitations are associated with their use, including instability, low solubility and permeability, poor gastrointestinal digestion, and low bioavailability. In this review, nano-carriers (e.g., liposome, polymersome, exosome, halloysite nanotubes, dendrimer, and nano-niosome, etc.) were summarized as anthocyanins delivery vehicles to treat inflammatory bowel disease. Recent progress on emerging strategies involved surface functionalization, responsive release, magnetic orientation, and self-assembly aggregation to address intestinal inflammation through nano-carriers and potential mechanisms were discussed. Anthocyanins, water-soluble pigments linked by glycoside bonds have attracted attention to alleviate intestinal inflammation related diseases. Anthocyanins can address intestinal inflammation by exerting their health beneficial effects such as anti-oxidative, anti-inflammatory, regulating the intestinal flora, and promoting apoptosis. Moreover, nano-carriers were discussed as oral delivery system for maximized bioefficacy of anthocyanins and to address concerns related to their low solubility and permeability, poor gastrointestinal metabolism, and low bioavailability were discussed. A future perspective is proposed concerning anthocyanin-loaded nano-carriers, different strategies to improve their efficacy, and developing functional food to treat intestinal inflammation.
Collapse
Affiliation(s)
- Hao Zhong
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Xin Luo
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Abdullah
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Xiaofeng Liu
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Muhammad Hussain
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| | - Rongfa Guan
- College of Food Science and Technology, Zhejiang University of Technology, Hangzhou, China
| |
Collapse
|
|
3
|
Dobani S, Kirsty Pourshahidi L, Ternan NG, McDougall GJ, Pereira-Caro G, Bresciani L, Mena P, Almutairi TM, Crozier A, Tuohy KM, Del Rio D, Gill CIR. A review on the effects of flavan-3-ols, their metabolites, and their dietary sources on gut barrier integrity. Food Funct 2025; 16:815-830. [PMID: 39807528 DOI: 10.1039/d4fo04721d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Impairment of gut barrier integrity is associated with the pathogenesis of gastrointestinal diseases, including inflammatory bowel disease, colorectal cancer, and coeliac disease. While many aspects of diet have been linked to improved barrier function, (poly)phenols, a broad group of bioactive phytochemicals, are of potential interest. The (poly)phenolic sub-class, flavan-3-ols, have been investigated in some detail owing to their abundance in commonly consumed foods, including grapes, tea, apples, cocoa, berries, and nuts. This review summarises studies on the effects of flavan-3-ols, their microbiome-mediated metabolites, and food sources of these compounds, on gut barrier structure. Extensive evidence demonstrates that flavan-3-ol rich foods, individual flavan-3-ols (e.g., (epi)catechin, epi(gallo)catechin-3-O-gallate, and pro(antho)cyanidins), and their related microbiota-mediated metabolites, could be effective in protecting and restoring the integrity of the gut barrier. In this context, various endpoints are assessed, including transepithelial electrical resistance of the epithelial layer and expression of tight junction proteins and mucins, in ex vivo, in vitro, and animal models. The differences in bioactivity reported for barrier integrity are structure-function dependent, related to the (poly)phenolic source or the tested compound, as well as their dose, exposure time, and presence or absence of a stressor in the experimental system. Overall, these results suggest that flavan-3-ols and related compounds could help to maintain, protect, and restore gut barrier integrity, indicating that they might contribute to the beneficial properties associated with the intake of their dietary sources. However, rigorous and robustly designed human intervention studies are needed to confirm these experimental observations.
Collapse
Affiliation(s)
- Sara Dobani
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK.
| | - L Kirsty Pourshahidi
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK.
| | - Nigel G Ternan
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK.
| | - Gordon J McDougall
- Environmental and Biochemical Sciences Department, The James Hutton Institute, Invergowrie, Dundee, UK
| | - Gema Pereira-Caro
- Department of Agroindustry and Food Quality, IFAPA-Alameda Del Obispo, Córdoba, Spain
| | - Letizia Bresciani
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Parma, Italy
| | - Pedro Mena
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Parma, Italy
- Microbiome Research Hub, Department of Food and Drug, University of Parma, Parma, Italy
| | | | - Alan Crozier
- Department of Chemistry, King Saud University Riyadh, Saudi Arabia
- School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
| | - Kieran M Tuohy
- School of Food Science & Nutrition, University of Leeds, Leeds, UK
| | - Daniele Del Rio
- Human Nutrition Unit, Department of Food and Drug, University of Parma, Parma, Italy
- Microbiome Research Hub, Department of Food and Drug, University of Parma, Parma, Italy
| | - Chris I R Gill
- Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, UK.
| |
Collapse
|
|
4
|
Gao X, Feng X, Hou T, Huang W, Ma Z, Zhang D. The roles of flavonoids in the treatment of inflammatory bowel disease and extraintestinal manifestations: A review. FOOD BIOSCI 2024; 62:105431. [DOI: 10.1016/j.fbio.2024.105431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
5
|
Xavier LEMDS, Reis TCG, Martins ASDP, Santos JCDF, Bueno NB, Goulart MOF, Moura FA. Antioxidant Therapy in Inflammatory Bowel Diseases: How Far Have We Come and How Close Are We? Antioxidants (Basel) 2024; 13:1369. [PMID: 39594511 PMCID: PMC11590966 DOI: 10.3390/antiox13111369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 11/01/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) pose a growing public health challenge with unclear etiology and limited efficacy of traditional pharmacological treatments. Alternative therapies, particularly antioxidants, have gained scientific interest. This systematic review analyzed studies from MEDLINE, Cochrane, Web of Science, EMBASE, and Scopus using keywords like "Inflammatory Bowel Diseases" and "Antioxidants." Initially, 925 publications were identified, and after applying inclusion/exclusion criteria-covering studies from July 2015 to June 2024 using murine models or clinical trials in humans and evaluating natural or synthetic substances affecting oxidative stress markers-368 articles were included. This comprised 344 animal studies and 24 human studies. The most investigated antioxidants were polyphenols and active compounds from medicinal plants (n = 242; 70.3%). The review found a strong link between oxidative stress and inflammation in IBD, especially in studies on nuclear factor kappa B and nuclear factor erythroid 2-related factor 2 pathways. However, it remains unclear whether inflammation or oxidative stress occurs first in IBD. Lipid peroxidation was the most studied oxidative damage, followed by DNA damage. Protein damage was rarely investigated. The relationship between antioxidants and the gut microbiota was examined in 103 animal studies. Human studies evaluating oxidative stress markers were scarce, reflecting a major research gap in IBD treatment. PROSPERO registration: CDR42022335357 and CRD42022304540.
Collapse
Affiliation(s)
| | | | - Amylly Sanuelly da Paz Martins
- Postgraduate Studies at the Northeast Biotechnology Network (RENORBIO), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil;
| | - Juliana Célia de Farias Santos
- Postgraduate Degree in Medical Sciences (PPGCM/UFAL), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil;
| | - Nassib Bezerra Bueno
- Postgraduate Degree in Nutrition (PPGNUT), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil; (L.E.M.d.S.X.); (N.B.B.)
| | - Marília Oliveira Fonseca Goulart
- Postgraduate Studies at the Northeast Biotechnology Network (RENORBIO), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil;
- Institute of Chemistry and Biotechnology (IQB/UFAL), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil
| | - Fabiana Andréa Moura
- Postgraduate Degree in Nutrition (PPGNUT), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil; (L.E.M.d.S.X.); (N.B.B.)
- Postgraduate Degree in Medical Sciences (PPGCM/UFAL), Federal University of Alagoas (UFAL), Maceió 57072-970, AL, Brazil;
| |
Collapse
|
|
6
|
Marino M, Rendine M, Venturi S, Porrini M, Gardana C, Klimis-Zacas D, Riso P, Del Bo' C. Red raspberry ( Rubus idaeus) preserves intestinal barrier integrity and reduces oxidative stress in Caco-2 cells exposed to a proinflammatory stimulus. Food Funct 2024; 15:6943-6954. [PMID: 38855989 DOI: 10.1039/d4fo01050g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Growing evidence showed the capacity of (poly)phenols to exert a protective role on intestinal health. Nevertheless, the existing findings are still heterogeneous and the underlying mechanisms remain unclear. This study investigated the potential benefits of a red raspberry (Rubus idaeus) powder on the integrity of the intestinal barrier, focusing on its ability to mitigate the effects of tumor necrosis factor-α (TNF-α)-induced intestinal permeability. Human colorectal adenocarcinoma cells (i.e., Caco-2 cells) were used as a model to assess the impact of red raspberry on intestinal permeability, tight junction expression, and oxidative stress. The Caco-2 cells were differentiated into polarized monolayers and treated with interferon-γ (IFN-γ) (10 ng mL-1) for 24 hours, followed by exposure to TNF-α (10 ng mL-1) in the presence or absence of red raspberry extract (1-5 mg mL-1). The integrity of the intestinal monolayer was evaluated using transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FITC-D) efflux assay. Markers of intestinal permeability (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG) and protein carbonyl) were assessed using ELISA kits. Treatment with red raspberry resulted in a significant counteraction of TEER value loss (41%; p < 0.01) and a notable reduction in the efflux of FITC-D (-2.5 times; p < 0.01). Additionally, red raspberry attenuated the levels of 8-OHdG (-48.8%; p < 0.01), mitigating the detrimental effects induced by TNF-α. Moreover, red raspberry positively influenced the expression of the integral membrane protein claudin-1 (+18%; p < 0.01), an essential component of tight junctions. These findings contribute to the growing understanding of the beneficial effects of red raspberry in the context of the intestinal barrier. The effect of red raspberry against TNF-α-induced intestinal permeability observed in our in vitro model suggests, for the first time, its potential as a dietary strategy to promote gastrointestinal health.
Collapse
Affiliation(s)
- Mirko Marino
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | - Marco Rendine
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | - Samuele Venturi
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | - Marisa Porrini
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | - Claudio Gardana
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | | | - Patrizia Riso
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| | - Cristian Del Bo'
- Università degli Studi di Milano, DeFENS - Department of Food, Environmental and Nutritional Sciences, Via Celoria 2, 20133 Milano, Italy.
| |
Collapse
|
|
7
|
Dharmawansa KVS, Stadnyk AW, Rupasinghe HPV. Dietary Supplementation of Haskap Berry ( Lonicera caerulea L.) Anthocyanins and Probiotics Attenuate Dextran Sulfate Sodium-Induced Colitis: Evidence from an Experimental Animal Model. Foods 2024; 13:1987. [PMID: 38998493 PMCID: PMC11241346 DOI: 10.3390/foods13131987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 06/10/2024] [Accepted: 06/20/2024] [Indexed: 07/14/2024] Open
Abstract
Haskap berry (Lonicera caerulea L.) is a rich dietary source of anthocyanins with potent anti-inflammatory properties. In this study, isolated haskap berry anthocyanins were encapsulated in maltodextrin and inulin (3:1) by freeze-drying to improve stability and bioavailability. The structural properties of microcapsules, encapsulation yield, efficiency, recovery, and powder retention were evaluated. The microcapsules that exhibited the highest encapsulation efficiency (60%) and anthocyanin recovery (89%) were used in the dextran sulfate sodium (DSS)-induced acute colitis in mice. Thirty-five BALB/c male mice of seven weeks old were divided into seven dietary supplementation groups (n = 5) to receive either free anthocyanins, encapsulated anthocyanins (6.2 mg/day), or probiotics (1 × 109 CFU/day) alone or as combinations of anthocyanin and probiotics. As observed by clinical data, free anthocyanin and probiotic supplementation significantly reduced the severity of colitis. The supplementary diets suppressed the DSS-induced elevation of serum inflammatory (interleukin (IL)-6 and tumor necrosis factor) and apoptosis markers (B-cell lymphoma 2 and Bcl-2-associated X protein) in mice colon tissues. The free anthocyanins and probiotics significantly reduced the serum IL-6 levels. In conclusion, the dietary supplementation of haskap berry anthocyanins and probiotics protects against DSS-induced colitis possibly by attenuating mucosal inflammation, and this combination has the potential as a health-promoting dietary supplement and nutraceutical.
Collapse
Affiliation(s)
- K V Surangi Dharmawansa
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada
| | - Andrew W Stadnyk
- Departments of Microbiology & Immunology and Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
| | - H P Vasantha Rupasinghe
- Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada
- Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada
| |
Collapse
|
|
8
|
Jianu EM, Pop RM, Gherman LM, Ranga F, Levai AM, Rus V, Bolboacă SD, Ștefan RA, Onofrei MM, Nati ID, Stoia IA, Ștefan PA, Mihu C, Mihu CM. The Effect of Rubus idaeus Polyphenols Extract in Induced Endometriosis in Rats. Molecules 2024; 29:778. [PMID: 38398530 PMCID: PMC10893551 DOI: 10.3390/molecules29040778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Endometriosis is a common gynecological condition with a complex physio-pathological background. This study aimed to assess the role of Rubus idaeus leaf extract (RiDE) as a potential therapeutic agent in reducing the size of the endometriotic lesions and modulate the plasma expression of MMP-2, MMP-9, and TGF-β1. The endometriotic lesions were induced in a rat model by the autologous transplant of endometrium. Thirty-six female rats, Wistar breed, with induced endometriosis, were divided into four groups and underwent treatment for 28 days. The CTRL group received 0.5 mL/day of the vehicle; the DG group received 1 mg/kg b.w./day dienogest; the RiDG group received 0.25 mL/kg b.w./day RiDE and the D+RiDG group received 1 mg/kg b.w./day dienogest and 0.25 mL/kg b.w./day RiDE, respectively. Rats' weight, endometriotic lesion diameter and grade, and plasma levels of MMP-2, MMP-9, and TGF-β1 were assessed before and after treatment. The administration of RiDE in association with dienogest vs. dienogest determined a lower weight gain and a reduction in diameter of the endometriotic lesions. RiDE administration restored MMP2 and MMP9 plasma levels to initial conditions. Rubus idaeus extract may help in reducing dienogest-associated weight gain, lower the size of endometriotic lesions, and have anti-inflammatory effects through MMP2 and MMP9 reduction.
Collapse
Affiliation(s)
- Elena-Mihaela Jianu
- Histology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (E.-M.J.); (R.-A.Ș.); (M.M.O.); (C.M.M.)
| | - Raluca Maria Pop
- Pharmacology, Toxicology and Clinical Pharmacology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania;
| | - Luciana Mădălina Gherman
- Experimental Centre, “Iuliu Haţieganu” University of Medicine and Pharmacy, Louis Pasteur, No 6, 400349 Cluj-Napoca, Romania
| | - Floricuța Ranga
- Food Science and Technology, Department of Food Science, University of Agricultural Science and Veterinary Medicine, Calea Mănăștur, No 3-5, 400372 Cluj-Napoca, Romania;
| | - Antonia-Mihaela Levai
- Obstetrics and Gynecology, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (A.-M.L.); (I.-D.N.)
| | - Vasile Rus
- Department of Cell Biology, Histology and Embryology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăștur, No 3-5, 400372 Cluj-Napoca, Romania;
| | - Sorana D. Bolboacă
- Department of Medical Informatics and Biostatistics, “Iuliu Haţieganu” University of Medicine and Pharmacy, Louis Pasteur, No 6, 400349 Cluj-Napoca, Romania;
| | - Roxana-Adelina Ștefan
- Histology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (E.-M.J.); (R.-A.Ș.); (M.M.O.); (C.M.M.)
| | - Mădălin Mihai Onofrei
- Histology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (E.-M.J.); (R.-A.Ș.); (M.M.O.); (C.M.M.)
| | - Ionel-Daniel Nati
- Obstetrics and Gynecology, Department of Mother and Child, “Iuliu Hatieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (A.-M.L.); (I.-D.N.)
| | - Ioana Alexandra Stoia
- Obstetrics and Gynaecology Department County Emergency Hospital, Clinicilor, No 3-5, 400006 Cluj-Napoca, Romania;
| | - Paul-Andrei Ștefan
- Anatomy and Embryology, Department of Morphological Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania;
| | - Carina Mihu
- Pharmacology, Toxicology and Clinical Pharmacology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania;
| | - Carmen Mihaela Mihu
- Histology, Department of Morphofunctional Sciences, “Iuliu Haţieganu” University of Medicine and Pharmacy, Victor Babeș, No 8, 400012 Cluj-Napoca, Romania; (E.-M.J.); (R.-A.Ș.); (M.M.O.); (C.M.M.)
| |
Collapse
|
|
9
|
Li Q, Lin L, Zhang C, Zhang H, Ma Y, Qian H, Chen XL, Wang X. The progression of inorganic nanoparticles and natural products for inflammatory bowel disease. J Nanobiotechnology 2024; 22:17. [PMID: 38172992 PMCID: PMC10763270 DOI: 10.1186/s12951-023-02246-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.
Collapse
Affiliation(s)
- Qingrong Li
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Liting Lin
- School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Provincial Institute of Translational Medicine, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Cong Zhang
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China
| | - Hengguo Zhang
- Key Laboratory of Oral Diseases Research of Anhui Province, College and Hospital of Stomatology, Anhui Medical University, Hefei, 230032, People's Republic of China
| | - Yan Ma
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China
| | - Haisheng Qian
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.
| | - Xu-Lin Chen
- Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
| | - Xianwen Wang
- Division of Gastroenterology, Division of Life Science and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230026, People's Republic of China.
| |
Collapse
|
|
10
|
Yuan Y, Wang F, Liu X, Shuai B, Fan H. The Role of AMPK Signaling in Ulcerative Colitis. Drug Des Devel Ther 2023; 17:3855-3875. [PMID: 38170149 PMCID: PMC10759424 DOI: 10.2147/dddt.s442154] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 12/22/2023] [Indexed: 01/05/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients' quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.
Collapse
Affiliation(s)
- Yuyi Yuan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Fang Wang
- Department of Rehabilitation Medicine, Jingshan Union Hospital, Union Hospital, Huazhong University of Science and Technology, Jingshan, Hubei, 431800, People’s Republic of China
| | - Xingxing Liu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Bo Shuai
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| | - Heng Fan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China
| |
Collapse
|
|
11
|
Sahoo DK, Heilmann RM, Paital B, Patel A, Yadav VK, Wong D, Jergens AE. Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. Front Endocrinol (Lausanne) 2023; 14:1217165. [PMID: 37701897 PMCID: PMC10493311 DOI: 10.3389/fendo.2023.1217165] [Citation(s) in RCA: 110] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 08/07/2023] [Indexed: 09/14/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.
Collapse
Affiliation(s)
- Dipak Kumar Sahoo
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Romy M. Heilmann
- Department for Small Animals, Veterinary Teaching Hospital, College of Veterinary Medicine, University of Leipzig, Leipzig, SN, Germany
| | - Biswaranjan Paital
- Redox Regulation Laboratory, Department of Zoology, College of Basic Science and Humanities, Odisha University of Agriculture and Technology, Bhubaneswar, India
| | - Ashish Patel
- Department of Life Sciences, Hemchandracharya North Gujarat University, Patan, Gujarat, India
| | - Virendra Kumar Yadav
- Department of Life Sciences, Hemchandracharya North Gujarat University, Patan, Gujarat, India
| | - David Wong
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Albert E. Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| |
Collapse
|
|
12
|
Lonicera caerulea polyphenols inhibit fat absorption by regulating Nrf2-ARE pathway mediated epithelial barrier dysfunction and special microbiota. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2022.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
|
|
13
|
Wu F, Wuri G, Fang B, Shi M, Zhang M, Zhao L. Alleviative mechanism and effect of Bifidobacterium animalisA6 on dextran sodium sulfate-induced ulcerative colitis in mice. Food Sci Nutr 2023; 11:892-902. [PMID: 36789079 PMCID: PMC9922152 DOI: 10.1002/fsn3.3124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 10/18/2022] [Accepted: 10/25/2022] [Indexed: 11/10/2022] Open
Abstract
Probiotics have been increasingly investigated for their role in alleviating symptoms of ulcerative colitis (UC), but the specific mechanism involved remains unclear. We investigated the alleviating effect of Bifidobacterium animalis A6 (BAA6) in UC through a mouse dextran sulfate sodium (DSS) model. When treated with a high dose of BAA6 (1 × 1010 cfu/ml), it was found that colitis symptoms were significantly alleviated, and mucosal damages experienced obvious relief. Moreover, a high dose of BAA6 effectively upregulated free fatty acid receptors 2 and 3 (FFAR2 and FFAR3) expression and butyric acid metabolism specifically. Furthermore, the supplement of BAA6 significantly suppressed pro-inflammatory cytokines levels (interleukin-13) and the expression of pore-forming protein claudin-2. The upstream regulatory genes of claudin-2, such as STAT6, GATA4, Cdx2, were also significantly inhibited by BAA6. Collectively, this study concludes that BAA6 attenuated DSS-induced colitis by increasing the levels of intestinal butyric acid, activating the butyric acid-FFAR pathway, suppressing excessive proinflammatory response, and protecting the function of the colon epithelial barrier.
Collapse
Affiliation(s)
- Fang Wu
- School of Food and HealthBeijing Technology and Business UniversityBeijingChina
| | - Guna Wuri
- School of Food and HealthBeijing Technology and Business UniversityBeijingChina
| | - Bing Fang
- The Innovation Centre of Food Nutrition and Human Health (Beijing)College of Food Science and Nutritional Engineering; China Agricultural UniversityBeijingChina
- Beijing Laboratory of Food Quality and SafetyCollege of Food Science and Nutritional Engineering, China Agricultural UniversityBeijingChina
| | - Mengxuan Shi
- The Innovation Centre of Food Nutrition and Human Health (Beijing)College of Food Science and Nutritional Engineering; China Agricultural UniversityBeijingChina
- Beijing Laboratory of Food Quality and SafetyCollege of Food Science and Nutritional Engineering, China Agricultural UniversityBeijingChina
| | - Ming Zhang
- School of Food and HealthBeijing Technology and Business UniversityBeijingChina
| | - Liang Zhao
- The Innovation Centre of Food Nutrition and Human Health (Beijing)College of Food Science and Nutritional Engineering; China Agricultural UniversityBeijingChina
- Key Laboratory of Functional DairyCollege of Food Science and Nutritional Engineering, China Agricultural UniversityBeijingChina
| |
Collapse
|
|
14
|
Jian S, Yang K, Zhang L, Zhang L, Xin Z, Wen C, He S, Deng J, Deng B. The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis. FOOD FRONTIERS 2023. [DOI: 10.1002/fft2.209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Affiliation(s)
- Shiyan Jian
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Kang Yang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Lingna Zhang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Limeng Zhang
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Zhongquan Xin
- Faculty of Food Science and Engineering Kunming University of Science and Technology Kunming China
| | - Chaoyu Wen
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Shansong He
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Jinping Deng
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| | - Baichuan Deng
- Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science South China Agricultural University Guangzhou China
| |
Collapse
|
|
15
|
Aleman RS, Moncada M, Aryana KJ. Leaky Gut and the Ingredients That Help Treat It: A Review. Molecules 2023; 28:619. [PMID: 36677677 PMCID: PMC9862683 DOI: 10.3390/molecules28020619] [Citation(s) in RCA: 78] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/31/2022] [Accepted: 01/01/2023] [Indexed: 01/11/2023] Open
Abstract
The human body is in daily contact with potentially toxic and infectious substances in the gastrointestinal tract (GIT). The GIT has the most significant load of antigens. The GIT can protect the intestinal integrity by allowing the passage of beneficial agents and blocking the path of harmful substances. Under normal conditions, a healthy intestinal barrier prevents toxic elements from entering the blood stream. However, factors such as stress, an unhealthy diet, excessive alcohol, antibiotics, and drug consumption can compromise the composition of the intestinal microbiota and the homeostasis of the intestinal barrier function of the intestine, leading to increased intestinal permeability. Intestinal hyperpermeability can allow the entry of harmful agents through the junctions of the intestinal epithelium, which pass into the bloodstream and affect various organs and systems. Thus, leaky gut syndrome and intestinal barrier dysfunction are associated with intestinal diseases, such as inflammatory bowel disease and irritable bowel syndrome, as well as extra-intestinal diseases, including heart diseases, obesity, type 1 diabetes mellitus, and celiac disease. Given the relationship between intestinal permeability and numerous conditions, it is convenient to seek an excellent strategy to avoid or reduce the increase in intestinal permeability. The impact of dietary nutrients on barrier function can be crucial for designing new strategies for patients with the pathogenesis of leaky gut-related diseases associated with epithelial barrier dysfunctions. In this review article, the role of functional ingredients is suggested as mediators of leaky gut-related disorders.
Collapse
Affiliation(s)
- Ricardo Santos Aleman
- School of Nutrition and Food Sciences, Louisiana State University Agricultural Center, Baton Rouge, LA 28081, USA
| | - Marvin Moncada
- Department of Food, Bioprocessing & Nutrition Sciences and the Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, Kannapolis, NC 27599, USA
| | - Kayanush J. Aryana
- School of Nutrition and Food Sciences, Louisiana State University Agricultural Center, Baton Rouge, LA 28081, USA
| |
Collapse
|
|
16
|
Broccoli-Derived Glucoraphanin Activates AMPK/PGC1α/NRF2 Pathway and Ameliorates Dextran-Sulphate-Sodium-Induced Colitis in Mice. Antioxidants (Basel) 2022; 11:antiox11122404. [PMID: 36552612 PMCID: PMC9774969 DOI: 10.3390/antiox11122404] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/30/2022] [Accepted: 12/01/2022] [Indexed: 12/11/2022] Open
Abstract
As the prevalence of inflammatory bowel diseases (IBD) rises, the etiology of IBD draws increasing attention. Glucoraphanin (GRP), enriched in cruciferous vegetables, is a precursor of sulforaphane, known to have anti-inflammatory and antioxidative effects. We hypothesized that dietary GRP supplementation can prevent mitochondrial dysfunction and oxidative stress in an acute colitis mouse model induced by dextran sulfate sodium (DSS). Eight-week-old mice were fed a regular rodent diet either supplemented with or without GRP. After 4 weeks of dietary treatments, half of the mice within each dietary group were subjected to 2.5% DSS treatment to induce colitis. Dietary GRP decreased DSS-induced body weight loss, disease activity index, and colon shortening. Glucoraphanin supplementation protected the colonic histological structure, suppressed inflammatory cytokines, interleukin (IL)-1β, IL-18, and tumor necrosis factor-α (TNF-α), and reduced macrophage infiltration in colonic tissues. Consistently, dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α, and nuclear factor erythroid 2-related factor 2 (NRF2) pathways in the colonic tissues of DSS-treated mice, which was associated with increased mitochondrial DNA and decreased content of the oxidative product 8-hydroxydeoxyguanosine (8-OHDG), a nucleotide oxidative product of DNA. In conclusion, dietary GRP attenuated mitochondrial dysfunction, inflammatory response, and oxidative stress induced by DSS, suggesting that dietary GRP provides a dietary strategy to alleviate IBD symptoms.
Collapse
|
|
17
|
Zhang B, Zhang Y, Liu X, Yin J, Li X, Zhang X, Xing X, Wang J, Wang S. Differential Protective Effect of Resveratrol and Its Microbial Metabolites on Intestinal Barrier Dysfunction is Mediated by the AMPK Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:11301-11313. [PMID: 36066018 DOI: 10.1021/acs.jafc.2c04101] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The effectiveness of resveratrol (RES) on intestinal barrier dysfunction and colitis has been extensively studied. However, the specific effects of its microbial metabolites on gut barrier function remain unclear. Hence, we compared the protective effects of RES and its microbial metabolites dihydroresveratrol (DHR) and 3-(4-hydroxyphenyl)-propionic acid (4HPP) against intestinal barrier injury and colitis. Only 4HPP and RES significantly reduced paracellular permeability and the secretion of proinflammatory cytokines in lipopolysaccharides (LPS)-treated intestinal Caco-2 cells, which was consistent with the upregulation in tight junction (TJ) proteins. Furthermore, RES and 4HPP ameliorated intestinal barrier dysfunction and colonic inflammation in colitis mice, while DHR did not. In particular, the expressions of intestinal TJ proteins and Muc2 were restored by RES and 4HPP. The molecular mechanism involved the adenosine monophosphate-activated protein kinase (AMPK)-mediated activation of CDX2 and the regulation of the SIRT1/NF-κB pathway. These findings provide new insights into understanding the protective effects of RES against intestinal barrier damage and colitis.
Collapse
Affiliation(s)
- Bowei Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Yunhui Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Xiaoxia Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jia Yin
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Xiang Li
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Xuejiao Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Xiaolong Xing
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jin Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| |
Collapse
|
|
18
|
Zhang L, Tian G, Huang L, Zhou M, Zhu J, Yi L, Mi M. Pterostilbene attenuates intestinal epithelial barrier loss induced by high loading intensity of exercise. Front Nutr 2022; 9:965180. [PMID: 35990348 PMCID: PMC9386544 DOI: 10.3389/fnut.2022.965180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 07/11/2022] [Indexed: 11/15/2022] Open
Abstract
Mounting evidence suggested that high loading intensity of exercise might be detrimental to human health, especially the gastrointestinal tract. Pterostilbene (PTE), derived from grapes and blueberries, might reach a high concentration of intestinal contents. Our study aimed to evaluate PTE’s ability to prevent the loss of intestinal epithelial barrier in high loading intensity of exercise. The exercise model was established by the forced running of mice. An effective HPLC-UV method was developed to quantify PTE concentration in intestinal content. The mRNA changes were detected by quantitative polymerase chain reaction (qPCR). The structure of intestinal flora was analyzed by 16S rRNA sequencing. The PTE (100 mg/kg/d) could significantly attenuate exercise-induced intestinal epithelial barrier loss. Moreover, the HPLC-UV assay showed that the PTE concentration of intestinal content could last 12 h. Furthermore, the exercise increased the abundance of Alistipes, which was related to lipopolysaccharide (LPS) production but could not be reversed by PTE intervention. Besides, cell experiments showed that PTE could promote the expression of intestinal epithelial tight junction (TJ) molecules in vitro. In conclusion, PTE has a significant interest in preventing exercise-induced intestinal damage.
Collapse
Affiliation(s)
- Lidong Zhang
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guoliang Tian
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Li Huang
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Min Zhou
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jundong Zhu
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Long Yi
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Mantian Mi
- Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Institute of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| |
Collapse
|
|
19
|
Kan J, Wu F, Wang F, Zheng J, Cheng J, Li Y, Yang Y, Du J. Phytonutrients: Sources, bioavailability, interaction with gut microbiota, and their impacts on human health. Front Nutr 2022; 9:960309. [PMID: 36051901 PMCID: PMC9424995 DOI: 10.3389/fnut.2022.960309] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/11/2022] [Indexed: 12/13/2022] Open
Abstract
Phytonutrients are natural bioactive components present in the daily diet that can exert a positive impact on human health. Studies have shown that phytonutrients may act as antioxidants and improve metabolism after being ingested, which help to regulate physiological processes and prevent metabolic disorders and diseases. However, their efficacy is limited by their low bioavailability. The gut microbiota is symbiotic with humans and its abundance and profile are related to most diseases. Interestingly, studies have shown that the gut microbiota is associated with the metabolism of phytonutrients by converting them into small molecules that can be absorbed by the body, thereby enhancing their bioavailability. Furthermore, phytonutrients can modulate the composition of the gut microbiota, and therefore improve the host's health. Here, we focus on uncovering the mechanisms by which phytonutrients and gut microbiota play roles in health, and the interrelationships between phytonutrients and gut microbiota were summarized. We also reviewed the studies that reported the efficacy of phytonutrients in human health and the future directions.
Collapse
Affiliation(s)
- Juntao Kan
- Nutrilite Health Institute, Shanghai, China
| | - Feng Wu
- Sequanta Technologies Co., Ltd., Shanghai, China
| | | | | | - Junrui Cheng
- Department of Molecular and Structural Biochemistry, North Carolina State University, Kannapolis, NC, United States
| | - Yuan Li
- Sequanta Technologies Co., Ltd., Shanghai, China
| | - Yuexin Yang
- Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, China
- Yuexin Yang
| | - Jun Du
- Nutrilite Health Institute, Shanghai, China
- *Correspondence: Jun Du
| |
Collapse
|
|
20
|
Shi M, Yue Y, Ma C, Dong L, Chen F. Pasteurized Akkermansia muciniphila Ameliorate the LPS-Induced Intestinal Barrier Dysfunction via Modulating AMPK and NF-κB through TLR2 in Caco-2 Cells. Nutrients 2022; 14:nu14040764. [PMID: 35215413 PMCID: PMC8879293 DOI: 10.3390/nu14040764] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/06/2022] [Accepted: 02/09/2022] [Indexed: 01/27/2023] Open
Abstract
Akkermansia muciniphila is well known for the amelioration of inflammatory responses and restoration of intestinal barrier function. The beneficial effect of A. muciniphila occurred through contacting Toll-like receptor 2 (TLR2) on intestinal epithelial cells by wall components. In this case, the downstream mechanism of pasteurized A. muciniphila stimulating TLR2 for ameliorated intestinal barrier function is worth investigating. In this study, we evaluated the effect of live and pasteurized A. muciniphila on protecting the barrier dysfunction of Caco-2 intestinal epithelial cells induced by lipopolysaccharide (LPS). We discovered that both live and pasteurized A. muciniphila could attenuate an inflammatory response and improve intestinal barrier integrity in Caco-2 monolayers. We demonstrated that A. muciniphila enhances AMP-activated protein kinase (AMPK) activation and inhibits Nuclear Factor-Kappa B (NF-κB) activation through the stimulation of TLR2. Overall, we provided a specific mechanism for the probiotic effect of A. muciniphila on the intestinal barrier function of Caco-2 cells.
Collapse
Affiliation(s)
- Mengxuan Shi
- National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (M.S.); (Y.Y.); (C.M.); (L.D.)
| | - Yunshuang Yue
- Beijing DaBeiNong Biotechnology Co., Ltd., Beijing 100193, China
| | - Chen Ma
- National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (M.S.); (Y.Y.); (C.M.); (L.D.)
| | - Li Dong
- National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (M.S.); (Y.Y.); (C.M.); (L.D.)
| | - Fang Chen
- National Engineering Research Center for Fruit and Vegetable Processing, Key Laboratory of Fruits and Vegetables Processing Ministry of Agriculture, Engineering Research Centre for Fruits and Vegetables Processing Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; (M.S.); (Y.Y.); (C.M.); (L.D.)
- Correspondence: ; Tel.: +86-10-6273-7645
| |
Collapse
|
|
21
|
Li S, Jin Y, Fu W, Cox AD, Lee D, Reddivari L. Intermittent antibiotic treatment accelerated the development of colitis in IL-10 knockout mice. Biomed Pharmacother 2022; 146:112486. [PMID: 34891113 DOI: 10.1016/j.biopha.2021.112486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 11/22/2021] [Accepted: 11/30/2021] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND AND AIMS Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10-/-] mouse model. METHODS IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. RESULTS Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. CONCLUSIONS In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.
Collapse
Affiliation(s)
- Shiyu Li
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA
| | - Yusong Jin
- College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China
| | - Wenyi Fu
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA
| | - Abigail D Cox
- College of Veterinary Medicine, Purdue University, 625 Harrison Street West Lafayette, IN 47907, USA
| | - Dale Lee
- Seattle Children's Hospital, University of Washington, Seattle, WA 98105, USA
| | - Lavanya Reddivari
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA.
| |
Collapse
|
|
22
|
Moreno RU, Gonzalez-Sarrias A, Espin JC, Tomas-Barberan F, Janes ME, Cheng H, Finley JW, Greenway FL, Losso JN. Effects of red raspberry polyphenols and metabolites on biomarkers of inflammation and insulin resistance in type 2 diabetes: A pilot study. Food Funct 2022; 13:5166-5176. [DOI: 10.1039/d1fo02090k] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Berry fruits are rich in polyphenolic compounds (PCs) and may promote health benefits. Anthocyanin (ACNs) concentrations of red raspberry (RR)(Rubus idaeus) extracts were 887.6 ± 262.8 μg/g consisting mainly of...
Collapse
|
|
23
|
Li X, Wei T, Wu M, Chen F, Zhang P, Deng ZY, Luo T. Potential metabolic activities of raspberry ketone. J Food Biochem 2021; 46:e14018. [PMID: 34913499 DOI: 10.1111/jfbc.14018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/30/2021] [Accepted: 11/01/2021] [Indexed: 12/11/2022]
Abstract
Novel food and food compounds interventions have attracted a lot of attention nowadays for the prevention and treatment of metabolic diseases. Raspberry ketone (RK) is aromatic compound found within red fruits and berries, has been used as an over-the-counter product for weight loss. However, actually, the effect of RK on weight loss is still controversial, and the mechanism is largely unknown. Besides, in vivo and in vitro studies have demonstrated the beneficial effect of RK on the development of other metabolic diseases. In this review, we comprehensively highlighted the synthesis, bioavailability, and metabolism of RK, and summarized the progress made in our understanding of the potential biological activities of RK, including antiobesity, antidiabetes, cardioprotection, and hepatoprotection, as well as their underlying mechanisms. This paper provides a critical overview about the current findings and proposes the future studies in the area of RK on human health. PRACTICAL APPLICATIONS: Raspberry ketone (RK) has been used for weight control for years, but this effect is controversial considering food intake. Additionally, RK is beneficial for T2DM, liver and heart injury. The underlying mechanisms of the protective effect of RK including accelerating fatty acid oxidation, balancing serum glucose level, anti-inflammation, antioxidant process, and so on. In this context, we provide a comprehensive analysis of the benefits of RK against many metabolic diseases and discuss the underlying molecular mechanisms. We hope our work will be helpful for further researches on RK and improve its public recognition.
Collapse
Affiliation(s)
- Xiaoping Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Teng Wei
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Min Wu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Fang Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China.,School of Public Health, Nanchang University, Nanchang, China
| | - Peng Zhang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Ze-Yuan Deng
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| | - Ting Luo
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, China
| |
Collapse
|
|
24
|
Cao R, Wu X, Guo H, Pan X, Huang R, Wang G, Liu J. Naringin Exhibited Therapeutic Effects against DSS-Induced Mice Ulcerative Colitis in Intestinal Barrier-Dependent Manner. Molecules 2021; 26:6604. [PMID: 34771012 PMCID: PMC8588024 DOI: 10.3390/molecules26216604] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/20/2021] [Accepted: 10/29/2021] [Indexed: 01/08/2023] Open
Abstract
Naringin is a kind of multi-source food additive which has been explored broadly for its various biological activities and therapeutic potential. In the present study, the protective effect and mechanism of naringin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated. The results showed that naringin significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), colon length shortening, and colon pathological damage. The tissue and serum secretion of inflammatory cytokines, as well as the oxidative stress, were decreased accordingly upon naringin intervention. Naringin also decreased the proteins involved in inflammation and increased the expression of tight junction (TJ) proteins. Moreover, naringin increased the relative abundance of Firmicutes/Bacteroides and reduced the content of Proteobacteria to improve the intestinal flora disorder caused by DSS, which promotes the intestinal health of mice. It was concluded that naringin can significantly ameliorate the pathogenic symptoms of UC through inhibiting inflammatory response and regulating intestinal microbiota, which might be a promising natural therapeutic agent for the dietary treatment of UC and the improvement of intestinal symbiosis.
Collapse
Affiliation(s)
- Ruige Cao
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| | - Xing Wu
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| | - Hui Guo
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| | - Xin Pan
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| | - Rong Huang
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| | - Gangqiang Wang
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
- Hubei Key Laboratory of Radiation Chemistry and Functional Materials, Non-Power Nuclear Technology Collaborative Innovation Center, School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, China
| | - Jikai Liu
- School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, China; (R.C.); (X.W.); (H.G.); (X.P.)
| |
Collapse
|
|
25
|
Li S, Wang T, Fu W, Kennett M, Cox AD, Lee D, Vanamala JKP, Reddivari L. Role of Gut Microbiota in the Anti-Colitic Effects of Anthocyanin-Containing Potatoes. Mol Nutr Food Res 2021; 65:e2100152. [PMID: 34633750 DOI: 10.1002/mnfr.202100152] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/29/2021] [Indexed: 11/07/2022]
Abstract
SCOPE Anthocyanin-containing potatoes exert anti-inflammatory activity in colitic mice. Gut bacterial dysbiosis plays a critical role in ulcerative colitis. This study examined the extent to which the anti-colitic activity of anthocyanin-containing red/purple-fleshed potatoes depends on the gut bacteria using a chemically-induced rodent model of colitis with the intact and antibiotic-ablated microbiome. METHODS AND RESULTS Four-week-old male mice (C57BL6) are randomly assigned to the control diet or 20% purple-/red-fleshed potatoes supplemented diet group. The microbiota-ablated group received an antibiotic cocktail in drinking water. At week nine, colitis is induced by 2% dextran sulfate sodium (DSS) in drinking water for five days. Administration of antibiotics resulted in a 95% reduction in gut bacterial load and fecal SCFAs. DSS-induced elevated gut permeability and body weight loss are more pronounced in antibiotic mice compared to non-antibiotic mice. Purple- or red-fleshed potato supplementation (20% w/w) ameliorated DSS-induced reduction in colon length and mucin 2 expression levels, and increase in permeability, spleen weight, myeloperoxidase (MPO) activity, and inflammatory cytokines (IL-6, IL-17, and IL1-β) expression levels in non-antibiotic mice, but not in gut microbiota ablated mice. CONCLUSIONS Anthocyanin-containing potatoes are potent in alleviating colitis, and the gut microbiome is critical for the anti-colitic activity of anthocyanin-containing potatoes.
Collapse
Affiliation(s)
- Shiyu Li
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN, 47907, USA
| | - Tianmin Wang
- Department of Plant Science, Penn State University, University Park, PA, 16802, USA
| | - Wenyi Fu
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN, 47907, USA
| | - Mary Kennett
- Department of Veterinary and Biomedical Sciences, Penn State University, University Park, PA, 16802, USA
| | - Abigail D Cox
- College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, IN, 47907, USA
| | - Dale Lee
- Seattle Children's Hospital, University of Washington, Seattle, WA, 98105, USA
| | - Jairam K P Vanamala
- Department of Food Science, Penn State University, University Park, PA, 16802, USA
| | - Lavanya Reddivari
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN, 47907, USA
| |
Collapse
|
|
26
|
Mármol I, Quero J, Ibarz R, Ferreira-Santos P, Teixeira JA, Rocha CM, Pérez-Fernández M, García-Juiz S, Osada J, Martín-Belloso O, Rodríguez-Yoldi MJ. Valorization of agro-food by-products and their potential therapeutic applications. FOOD AND BIOPRODUCTS PROCESSING 2021. [DOI: 10.1016/j.fbp.2021.06.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
27
|
Yang X, Mao Z, Huang Y, Yan H, Yan Q, Hong J, Fan J, Yao J. Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state. Redox Biol 2021; 41:101881. [PMID: 33601276 PMCID: PMC7897995 DOI: 10.1016/j.redox.2021.101881] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/22/2020] [Accepted: 01/22/2021] [Indexed: 01/16/2023] Open
Abstract
Albumin (Alb) is the most abundant plasma protein with multiple biological functions, including antioxidative property through its thiol activity. Given that inflammatory bowel disease is associated with a decreased level of Alb and an increased level of Alb oxidation, we asked whether Alb could have a therapeutic effect on colitis. Here we tested this possibility. Bovine serum albumin (BSA) was reductively modified with dithiothreitol (DTT) and administrated via gavage or intraperitoneal injection. Dextran sulfate sodium (DSS)-induced mice colitis was associated with massive oxidative stress, as indicated by the elevated sulfenic acid formation in blood, colon tissues, and feces. Treatment of mice with the reductively modified albumin (r-Alb) attenuated the oxidative stress and reduced local inflammation and tissue injury. These effects of r-Alb were only partially achieved by unmodified Alb and wholly lost after blocking the -SH groups with maleimide. In cultured colon epithelial cells, r-Alb prevented DSS- and H2O2-induced ROS elevation and barrier dysfunction, preceded by inhibition of sulfenic acid formation and P38 activation. Further analysis revealed that Alb was susceptible to H2O2-induced oxidation, and it detoxified H2O2 in a -SH group-dependent way. Moreover, Alb reacted with GSH/GSSG via thiol-disulfide exchange and reciprocally regulated the availability of -SH groups. Collectively, our study shows that r-Alb effectively attenuates DSS colitis via -SH group-mediated antioxidative action. Given that the oxidative stress underlies many life-threatening diseases, r-Alb, functioning as a potent antioxidant, could have a wide range of applications.
Collapse
Affiliation(s)
- Xiawen Yang
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Zhimin Mao
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Yanru Huang
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Haizhao Yan
- Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Qiaojing Yan
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Jingru Hong
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Jianglin Fan
- Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Jian Yao
- Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
| |
Collapse
|
|
28
|
Chen G, Li Y, Li X, Zhou D, Wang Y, Wen X, Wang C, Liu X, Feng Y, Li B, Li N. Functional foods and intestinal homeostasis: The perspective of in vivo evidence. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.02.075] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
29
|
Tian Q, Bravo Iniguez A, Sun Q, Wang H, Du M, Zhu MJ. Dietary Alpha-Ketoglutarate Promotes Epithelial Metabolic Transition and Protects against DSS-Induced Colitis. Mol Nutr Food Res 2021; 65:e2000936. [PMID: 33547710 DOI: 10.1002/mnfr.202000936] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/12/2020] [Indexed: 12/13/2022]
Abstract
SCOPE As a natural compound in foods, alpha-ketoglutarate (aKG) is one of the key metabolites maintaining energy homeostasis. This study examines the beneficial effects of dietary aKG against the development of experimental colitis and further explores the underlying molecular mechanisms. METHODS AND RESULTS Eight-week-old male C57BL/6 mice receive drinking water with or without 1% aKG for 4 weeks. At week 3, colitis is induced by 2.5% dextran sulfate sodium (DSS) for 7 days followed by 7 days recovery. Dietary aKG supplementation decreases DSS-induced body weight loss, gross bleeding, fecal consistency score, and disease activity index. In agreement, aKG supplementation restores DSS-associated colon shortening, ameliorated mucosal damage, and macrophage infiltration into colonic tissue, which are associated with suppressed gut inflammation and Wnt signaling, and improved epithelial structure. Consistently, aKG supplementation enhances M1 to M2 macrophage polarization and strengthens intestinal barrier function. Additionally, aKG supplementation elevates colonic aKG levels while decreasing 2-hydroxyglutarate levels, which increases oxidative instead of glycolytic metabolism. CONCLUSION aKG supplementation protects against epithelial damage and ameliorates DSS-induced colitis, which are associated with suppressed inflammation, Wnt signaling pathway, and glycolysis. Intake of foods enriched with aKG or aKG supplementation can be an alternative approach for the prevention or treatment of colitis that are common in Western societies.
Collapse
Affiliation(s)
- Qiyu Tian
- School of Food Science, Washington State University, Pullman, WA, 99164, USA
- Department of Animal Science, Washington State University, Pullman, WA, 99164, USA
| | | | - Qi Sun
- School of Food Science, Washington State University, Pullman, WA, 99164, USA
| | - Hongbin Wang
- School of Food Science, Washington State University, Pullman, WA, 99164, USA
| | - Min Du
- Department of Animal Science, Washington State University, Pullman, WA, 99164, USA
| | - Mei-Jun Zhu
- School of Food Science, Washington State University, Pullman, WA, 99164, USA
| |
Collapse
|
|
30
|
Pistol GC, Bulgaru CV, Marin DE, Oancea AG, Taranu I. Dietary Grape Seed Meal Bioactive Compounds Alleviate Epithelial Dysfunctions and Attenuates Inflammation in Colon of DSS-Treated Piglets. Foods 2021; 10:foods10030530. [PMID: 33806347 PMCID: PMC7999447 DOI: 10.3390/foods10030530] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/25/2021] [Accepted: 02/27/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory Bowel Diseases (IBD) are chronic inflammations associated with progressive degradation of intestinal epithelium and impairment of the local innate immune response. Restoring of epithelial integrity and of the mucosal barrier function, together with modulation of inflammatory and innate immune markers, represent targets for alternative strategies in IBD. The aim of our study was to evaluate the effects of a diet including 8% grape seed meal (GSM), rich in bioactive compounds (polyphenols, polyunsaturated fatty acids (PUFAs), fiber) on the markers of colonic epithelial integrity, mucosal barrier function, pro-inflammatory, and innate immunity in DSS-treated piglets used as animal models of intestinal inflammation. Our results have demonstrated the beneficial effects of bioactive compounds from dietary GSM, exerted at three complementary levels: (a) restoration of the epithelial integrity and mucosal barrier reinforcement by modulation of claudins, Occludin (OCCL) and Zonula-1 (ZO-1) tight junction genes and proteins, myosin IXB (MYO9B) and protein tyrosine phosphatase (PTPN) tight junction regulators and mucin-2 (MUC2) gene; (b) reduction of pro-inflammatory MMP-2 (matrix metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9) genes and activities; and (c) suppression of the innate immune TLR-2 (Toll-like receptor-2) and TLR-4 (Toll-like receptor-4) genes and attenuation of the expression of MyD88 (Myeloid Differentiation Primary Response 88)/MD-2 (Myeloid differentiation factor-2) signaling molecules. These beneficial effects of GSM could further attenuate the transition of chronic colitis to carcinogenesis, by modulating the in-depth signaling mediators belonging to the Wnt pathway.
Collapse
Affiliation(s)
- Gina Cecilia Pistol
- Laboratory of Animal Biology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, 077015 Balotesti, Romania; (C.V.B.); (D.E.M.); (I.T.)
- Correspondence: ; Tel.: +40-21-351-2082
| | - Cristina Valeria Bulgaru
- Laboratory of Animal Biology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, 077015 Balotesti, Romania; (C.V.B.); (D.E.M.); (I.T.)
| | - Daniela Eliza Marin
- Laboratory of Animal Biology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, 077015 Balotesti, Romania; (C.V.B.); (D.E.M.); (I.T.)
| | - Alexandra Gabriela Oancea
- Laboratory of Chemistry and Nutrition Physiology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, 077015 Balotesti, Romania;
| | - Ionelia Taranu
- Laboratory of Animal Biology, INCDBNA-IBNA, National Institute of Research and Development for Biology and Animal Nutrition, 077015 Balotesti, Romania; (C.V.B.); (D.E.M.); (I.T.)
| |
Collapse
|
|
31
|
Internal connections between dietary intake and gut microbiota homeostasis in disease progression of ulcerative colitis: a review. FOOD SCIENCE AND HUMAN WELLNESS 2021. [DOI: 10.1016/j.fshw.2021.02.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
32
|
Olivier S, Pochard C, Diounou H, Castillo V, Divoux J, Alcantara J, Leclerc J, Guilmeau S, Huet C, Charifi W, Varin TV, Daniel N, Foretz M, Neunlist M, Salomon BL, Ghosh P, Marette A, Rolli-Derkinderen M, Viollet B. Deletion of intestinal epithelial AMP-activated protein kinase alters distal colon permeability but not glucose homeostasis. Mol Metab 2021; 47:101183. [PMID: 33548500 PMCID: PMC7921883 DOI: 10.1016/j.molmet.2021.101183] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/21/2021] [Accepted: 02/01/2021] [Indexed: 12/11/2022] Open
Abstract
Objective The intestinal epithelial barrier (IEB) restricts the passage of microbes and potentially harmful substances from the lumen through the paracellular space, and rupture of its integrity is associated with a variety of gastrointestinal disorders and extra-digestive diseases. Increased IEB permeability has been linked to disruption of metabolic homeostasis leading to obesity and type 2 diabetes. Interestingly, recent studies have uncovered compelling evidence that the AMP-activated protein kinase (AMPK) signaling pathway plays an important role in maintaining epithelial cell barrier function. However, our understanding of the function of intestinal AMPK in regulating IEB and glucose homeostasis remains sparse. Methods We generated mice lacking the two α1 and α2 AMPK catalytic subunits specifically in intestinal epithelial cells (IEC AMPK KO) and determined the physiological consequences of intestinal-specific deletion of AMPK in response to high-fat diet (HFD)-induced obesity. We combined histological, functional, and integrative analyses to ascertain the effects of gut AMPK loss on intestinal permeability in vivo and ex vivo and on the development of obesity and metabolic dysfunction. We also determined the impact of intestinal AMPK deletion in an inducible mouse model (i-IEC AMPK KO) by measuring IEB function, glucose homeostasis, and the composition of gut microbiota via fecal 16S rRNA sequencing. Results While there were no differences in in vivo intestinal permeability in WT and IEC AMPK KO mice, ex vivo transcellular and paracellular permeability measured in Ussing chambers was significantly increased in the distal colon of IEC AMPK KO mice. This was associated with a reduction in pSer425 GIV phosphorylation, a marker of leaky gut barrier. However, the expression of tight junction proteins in intestinal epithelial cells and pro-inflammatory cytokines in the lamina propria were not different between genotypes. Although the HFD-fed AMPK KO mice displayed suppression of the stress polarity signaling pathway and a concomitant increase in colon permeability, loss of intestinal AMPK did not exacerbate body weight gain or adiposity. Deletion of AMPK was also not sufficient to alter glucose homeostasis or the acute glucose-lowering action of metformin in control diet (CD)- or HFD-fed mice. CD-fed i-IEC AMPK KO mice also presented higher permeability in the distal colon under homeostatic conditions but, surprisingly, this was not detected upon HFD feeding. Alteration in epithelial barrier function in the i-IEC AMPK KO mice was associated with a shift in the gut microbiota composition with higher levels of Clostridiales and Desulfovibrionales. Conclusions Altogether, our results revealed a significant role of intestinal AMPK in maintaining IEB integrity in the distal colon but not in regulating glucose homeostasis. Our data also highlight the complex interaction between gut microbiota and host AMPK.
Deletion of intestinal AMPKα1 and α2 suppresses the stress-polarity signaling (SPS) pathway. Loss of the SPS pathway is associated with increased paracellular permeability in the distal colon. Intestinal AMPK is dispensable for the acute glucose-lowering action of metformin. Loss of intestinal AMPK alters the gut microbiota composition.
Collapse
Affiliation(s)
- Séverine Olivier
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Camille Pochard
- University of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France
| | - Hanna Diounou
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Vanessa Castillo
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Jordane Divoux
- Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Paris, France
| | - Joshua Alcantara
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Jocelyne Leclerc
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Sandra Guilmeau
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Camille Huet
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Wafa Charifi
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Thibault V Varin
- Québec Heart and Lung Research Institute (IUCPQ) & Institute for Nutrition and Functional Foods (INAF), Laval University Québec, Québec, Canada
| | - Noëmie Daniel
- Québec Heart and Lung Research Institute (IUCPQ) & Institute for Nutrition and Functional Foods (INAF), Laval University Québec, Québec, Canada
| | - Marc Foretz
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France
| | - Michel Neunlist
- University of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France
| | - Benoit L Salomon
- Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Paris, France
| | - Pradipta Ghosh
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - André Marette
- Québec Heart and Lung Research Institute (IUCPQ) & Institute for Nutrition and Functional Foods (INAF), Laval University Québec, Québec, Canada
| | - Malvyne Rolli-Derkinderen
- University of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France.
| | - Benoit Viollet
- Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France.
| |
Collapse
|
|
33
|
Eguchi H, Matsunaga H, Onuma S, Yoshino Y, Matsunaga T, Ikari A. Down-Regulation of Claudin-2 Expression by Cyanidin-3-Glucoside Enhances Sensitivity to Anticancer Drugs in the Spheroid of Human Lung Adenocarcinoma A549 Cells. Int J Mol Sci 2021; 22:ijms22020499. [PMID: 33419064 PMCID: PMC7825397 DOI: 10.3390/ijms22020499] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/31/2020] [Accepted: 01/04/2021] [Indexed: 12/15/2022] Open
Abstract
Claudin-2 (CLDN2), an integral membrane protein located at tight junctions, is abnormally expressed in human lung adenocarcinoma tissues, and is linked to drug resistance in human lung adenocarcinoma A549 cells. CLDN2 may be a target for the prevention of lung adenocarcinoma, but there are few compounds which can reduce CLDN2 expression. We found that cyanidin-3-glucoside (C3G), the anthocyanin with two hydroxyl groups on the B-ring, and cyanidin significantly reduce the protein level of CLDN2 in A549 cells. In contrast, pelargonidin-3-glucoside (P3G), the anthocyanin with one hydroxyl group on the B-ring, had no effect. These results suggest that cyanidin and the hydroxyl group at the 3-position on the B-ring play an important role in the reduction of CLDN2 expression. The phosphorylation of Akt, an activator of CLDN2 expression at the transcriptional level, was inhibited by C3G, but not by P3G. The endocytosis and lysosomal degradation are suggested to be involved in the C3G-induced decrease in CLDN2 protein expression. C3G increased the phosphorylation of p38 and the p38 inhibitor SB203580 rescued the C3G-induced decrease in CLDN2 expression. In addition, SB203580 rescued the protein stability of CLDN2. C3G may reduce CLDN2 expression at the transcriptional and post-translational steps mediated by inhibiting Akt and activating p38, respectively. C3G enhanced the accumulation and cytotoxicity of doxorubicin (DXR) in the spheroid models. The percentages of apoptotic and necrotic cells induced by DXR were increased by C3G. Our data suggest that C3G-rich foods can prevent the chemoresistance of lung adenocarcinoma A549 cells through the reduction of CLDN2 expression.
Collapse
Affiliation(s)
- Hiroaki Eguchi
- Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; (H.E.); (H.M.); (S.O.); (Y.Y.)
| | - Haruka Matsunaga
- Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; (H.E.); (H.M.); (S.O.); (Y.Y.)
| | - Saki Onuma
- Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; (H.E.); (H.M.); (S.O.); (Y.Y.)
| | - Yuta Yoshino
- Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; (H.E.); (H.M.); (S.O.); (Y.Y.)
| | - Toshiyuki Matsunaga
- Education Center of Green Pharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 502-8585, Japan;
| | - Akira Ikari
- Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan; (H.E.); (H.M.); (S.O.); (Y.Y.)
- Correspondence: ; Tel./Fax: +81-58-230-8124
| |
Collapse
|
|
34
|
|
|
35
|
Malcomson FC, Willis ND, McCallum I, Xie L, Shivappa N, Wirth MD, Hébert JR, Kocaadam-Bozkurt B, Özturan-Sirin A, Kelly SB, Bradburn DM, Belshaw NJ, Johnson IT, Mathers JC. Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber. Cancer Prev Res (Phila) 2020; 14:337-346. [PMID: 33115783 DOI: 10.1158/1940-6207.capr-20-0335] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/29/2020] [Accepted: 10/22/2020] [Indexed: 01/10/2023]
Abstract
Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, P = 0.03]. Baseline E-DII score correlated with FOSL1 (β = 0.503, P = 0.003) and WNT11 (β = 0.472, P = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. WNT11 expression was more than 2-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, P = 0.002). Baseline E-DII modulated the effects of PD supplementation on FOSL1 expression (P = 0.04). More proinflammatory diets were associated with altered WNT signaling and appeared to modulate the effects of PD supplementation on expression of FOSL1 This is the first study to investigate relationships between the E-DII and molecular markers of WNT signaling in rectal tissue of healthy individuals.Prevention Relevance: Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognized pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.
Collapse
Affiliation(s)
- Fiona C Malcomson
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom
| | - Naomi D Willis
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom
| | - Iain McCallum
- Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom
| | - Long Xie
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom
| | - Nitin Shivappa
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
| | - Michael D Wirth
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina.,College of Nursing, University of South Carolina, Columbia, South Carolina
| | - James R Hébert
- Department of Epidemiology and Biostatistics and Cancer Prevention and Control Program, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
| | - Betul Kocaadam-Bozkurt
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.,Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, Ankara, Turkey.,Department of Nutrition and Dietetics, Faculty of Health Sciences, Trakya University, Edirne, Turkey
| | - Aycil Özturan-Sirin
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.,Department of Nutrition and Dietetics, Faculty of Health Sciences, Adnan Menderes University, Aydin, Turkey
| | - Seamus B Kelly
- Northumbria Healthcare NHS Foundation Trust, North Shields, United Kingdom
| | | | - Nigel J Belshaw
- University of East Anglia, Norwich Research Park, Norwich, United Kingdom
| | - Ian T Johnson
- Quadram Institute, Norwich Research Park, Norwich, United Kingdom
| | - John C Mathers
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
| |
Collapse
|
|
36
|
Khan MS, Ikram M, Park JS, Park TJ, Kim MO. Gut Microbiota, Its Role in Induction of Alzheimer's Disease Pathology, and Possible Therapeutic Interventions: Special Focus on Anthocyanins. Cells 2020; 9:cells9040853. [PMID: 32244729 PMCID: PMC7226756 DOI: 10.3390/cells9040853] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 03/22/2020] [Accepted: 03/31/2020] [Indexed: 12/21/2022] Open
Abstract
The human gut is a safe environment for several microbes that are symbiotic and important for the wellbeing of human health. However, studies on gut microbiota in different animals have suggested that changes in the composition and structure of these microbes may promote gut inflammation by releasing inflammatory cytokines and lipopolysaccharides, gut-wall leakage, and may affect systemic inflammatory and immune mechanisms that are important for the normal functioning of the body. There are many factors that aid in the gut’s dysbiosis and neuroinflammation, including high stress levels, lack of sleep, fatty and processed foods, and the prolonged use of antibiotics. These neurotoxic mechanisms of dysbiosis may increase susceptibility to Alzheimer’s disease (AD) and other neurodegenerative conditions. Therefore, studies have recently been conducted to tackle AD-like conditions by specifically targeting gut microbes that need further elucidation. It was suggested that gut dyshomeostasis may be regulated by using available options, including the use of flavonoids such as anthocyanins, and restriction of the use of high-fatty-acid-containing food. In this review, we summarize the gut microbiota, factors promoting it, and possible therapeutic interventions especially focused on the therapeutic potential of natural dietary polyflavonoid anthocyanins. Our study strongly suggests that gut dysbiosis and systemic inflammation are critically involved in the development of neurodegenerative disorders, and the natural intake of these flavonoids may provide new therapeutic opportunities for preclinical or clinical studies.
Collapse
Affiliation(s)
- Muhammad Sohail Khan
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (M.S.K.); (M.I.); (J.S.P.)
| | - Muhammad Ikram
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (M.S.K.); (M.I.); (J.S.P.)
| | - Jun Sung Park
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (M.S.K.); (M.I.); (J.S.P.)
| | - Tae Ju Park
- Paul O’Gorman Leukaemia Research, Centre Institute of Cancer, Sciences University of Glasgow, 0747 657 5394 Glasgow, UK;
| | - Myeong Ok Kim
- Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea; (M.S.K.); (M.I.); (J.S.P.)
- Correspondence: ; Tel.: +82-55-772-1345; Fax: +82-55-772-2656
| |
Collapse
|
|
37
|
Zhou G, Chen L, Sun Q, Mo QG, Sun WC, Wang YW. Maqui berry exhibited therapeutic effects against DSS-induced ulcerative colitis in C57BL/6 mice. Food Funct 2020; 10:6655-6665. [PMID: 31556890 DOI: 10.1039/c9fo00663j] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Maqui berry (Aristotelia chilensis) is an edible berry. The study aimed to explore the therapeutic effect of maqui berry on inflammatory bowel disease. Maqui berry water extract was separated by multiple solvents extraction. The chemical bases, antioxidant and anti-inflammatory properties of different extract fractions were then compared. Dextran sodium sulfate (DSS)-induced ulcerative colitis mice were used for the pharmacological activity test in vivo. Experimental results showed that the ethyl acetate fraction of maqui berry water extract (MWE) was rich in phenols and exhibited good antioxidant and anti-inflammatory activities. MWE considerably reduced the expression of COX2 and IL-6 in LPS-stimulated RAW 264.7 cells. Inflammatory bowel disease index, MDA, NO, i-NOS, and COX2 in colon tissues and MPO, TNF-α, and IL-1β in blood serums were remarkably decreased in the treatment group compared to in the model group (p < 0.05). Intestinal histopathological damage was significantly alleviated in the treatment group, and the expression of occludin was increased (p < 0.05). MWE treatment alleviated the imbalance of gut microbiota caused by DSS injury. Overall, MWE plays a therapeutic role in ulcerative colitis through its anti-inflammatory effect, reduces immune stress, and regulates gut microbiota.
Collapse
Affiliation(s)
- Gao Zhou
- Institute of TCM and Natural Products, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, P.R. China.
| | | | | | | | | | | |
Collapse
|
|
38
|
Bao N, Chen F, Dai D. The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease. Front Immunol 2020; 10:2981. [PMID: 31969882 PMCID: PMC6960133 DOI: 10.3389/fimmu.2019.02981] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 12/04/2019] [Indexed: 12/13/2022] Open
Abstract
Polyphenols are essential antioxidants in our regular diet, and have shown potential antibacterial effects. Other important biological effects, such as anticancer or antibacterial activities, have been demonstrated by some polyphenols. In recent years, the benefits of polyphenols to human health have attracted increasing attention from the scientific community. Recent studies have shown that polyphenols such as anthocyanin, catechin, chlorogenic acid, and resveratrol can inhibit pathogenic bacteria such as Escherichia coli and Salmonella to help regulate intestinal microflora. An imbalance of intestinal microflora and the destruction of intestinal barrier function have been found to have a potential relationship with the occurrence of chronic kidney disease (CKD). Specifically, they can aberrantly trigger the immune system to cause inflammation, increase the production of uremic toxins, and further worsen the condition of CKD. Therefore, the maintenance of intestinal microflora and the intestinal tract in a stable and healthy state may be able to "immunize" patients against CKD, and treat pre-existing disease. The use of common antibiotics may lead to drug resistance in pathogens, and thus beneficial polyphenols may be suitable natural substitutes for antibiotics. Herein we review the ability of different polyphenols, such as anthocyanin, catechin, chlorogenic acid, and resveratrol, to regulate intestinal microorganisms, inhibit pathogenic bacteria, and improve inflammation. In addition, we review the ability of different polyphenols to reduce kidney injury, as described in recent studies.
Collapse
Affiliation(s)
- Naren Bao
- Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China
| | - Fangjie Chen
- Department of Medical Genetics, School of Life Sciences, China Medical University, Shenyang, China
| | - Di Dai
- Department of Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China
| |
Collapse
|
|
39
|
Amirshahrokhi K. Febuxostat attenuates ulcerative colitis by the inhibition of NF-κB, proinflammatory cytokines, and oxidative stress in mice. Int Immunopharmacol 2019; 76:105884. [PMID: 31499267 DOI: 10.1016/j.intimp.2019.105884] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 09/03/2019] [Accepted: 09/04/2019] [Indexed: 12/14/2022]
Abstract
Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative stress and upregulation of proinflammatory mediators in colonic tissue. Febuxostat, a xanthine oxidase inhibitor has been shown to exert anti-inflammatory and antioxidant effects. The aim of this study was to investigate the protective effect of febuxostat against ulcerative colitis, and to elucidate the potential mechanisms involved. Experimental colitis was induced in mice by intrarectal administration of 5% acetic acid. Mice were treated with febuxostat (10 and 20 mg/kg/day, orally) for three days. Results showed that body weight loss, colon shortening, macroscopic damage and histopathological changes of colonic mucosa were reduced in mice treated with febuxostat. Treatment of mice with febuxostat significantly increased the levels of glutathione (GSH) and superoxide dismutase (SOD), and decreased the levels of malondialdehyde (MDA), carbonyl protein, xanthine oxidase, nitric oxide (NO) and myeloperoxidase (MPO) activity of colon tissue compared with those in the acetic acid-induced colitis group. The expression of nuclear factor kappa B (NF-κB) as a key regulator of inflammation in the colonic tissue was decreased by febuxostat. Furthermore treatment with febuxostat significantly reduced the levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and interferon (IFN)-γ, while increased the levels of IL-10 compared with the colitis group. These results suggest that febuxostat is able to decrease the severity of acetic acid-induced colitis by inhibition of oxidative stress and inflammatory responses through NF-κB pathway.
Collapse
Affiliation(s)
- Keyvan Amirshahrokhi
- Department of Pharmacology, School of Pharmacy, Ardabil University of Medical Sciences, P. O. Box 5618953141, Ardabil, Iran.
| |
Collapse
|
|
40
|
Han Y, Song M, Gu M, Ren D, Zhu X, Cao X, Li F, Wang W, Cai X, Yuan B, Goulette T, Zhang G, Xiao H. Dietary Intake of Whole Strawberry Inhibited Colonic Inflammation in Dextran-Sulfate-Sodium-Treated Mice via Restoring Immune Homeostasis and Alleviating Gut Microbiota Dysbiosis. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:9168-9177. [PMID: 30810035 DOI: 10.1021/acs.jafc.8b05581] [Citation(s) in RCA: 93] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Strawberry (Fragaria chiloensis) is a major edible berry with various potential health benefits. This study determined the protective effects of whole strawberry (WS) against dextran-sulfate-sodium-induced colitis in mice. In colitic mice, dietary WS reduced the disease activity index, prevented the colon shortening and spleen enlargement, and alleviated the colonic tissue damages. The abundance of proinflammatory immune cells was reduced by dietary WS in the colonic mucosa, which was accompanied by the suppression of overproduction of proinflammatory cytokines. Western blotting and immunohistochemical analysis revealed that dietary WS decreased the expression of proinflammatory proteins in the colonic mucosa. Moreover, dietary WS partially reversed the alteration of gut microbiota in the colitic mice by increasing the abundance of potential beneficial bacteria, e.g., Bifidobacterium and Lactobacillus, and decreasing the abundance of potential harmful bacteria, e.g., Dorea and Bilophila. Dietary WS also restored the decreased production of short-chain fatty acids in the cecum of the colitic mice. The results revealed the anti-inflammatory effects and mechanisms of dietary WS in the colon, which is critical for the rational utilization of strawberry for the prevention of inflammation-driven diseases.
Collapse
Affiliation(s)
- Yanhui Han
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Mingyue Song
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
- College of Food Science , South China Agricultural University , Guangzhou , Guangdong 510642 , People's Republic of China
| | - Min Gu
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Daoyuan Ren
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
- College of Food Engineering and Nutritional Science , Shaanxi Normal University , Xi'an Shaanxi 710062 , People's Republic of China
| | - Xiaoai Zhu
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
- College of Food Science , South China Agricultural University , Guangzhou , Guangdong 510642 , People's Republic of China
| | - Xiaoqiong Cao
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Fang Li
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Weicang Wang
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Xiaokun Cai
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Biao Yuan
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Timothy Goulette
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Guodong Zhang
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| | - Hang Xiao
- Department of Food Science , University of Massachusetts , Amherst , Massachusetts 01003 , United States
| |
Collapse
|
|
41
|
Vargas-Robles H, Castro-Ochoa KF, Citalán-Madrid AF, Schnoor M. Beneficial effects of nutritional supplements on intestinal epithelial barrier functions in experimental colitis models in vivo. World J Gastroenterol 2019; 25:4181-4198. [PMID: 31435172 PMCID: PMC6700707 DOI: 10.3748/wjg.v25.i30.4181] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 06/12/2019] [Accepted: 07/05/2019] [Indexed: 02/06/2023] Open
Abstract
Acute and chronic colitis affect a huge proportion of the population world-wide. The etiology of colitis cases can be manifold, and diet can significantly affect onset and outcome of colitis. While many forms of acute colitis are easily treatable, chronic forms of colitis such as ulcerative colitis and Crohn's disease (summarized as inflammatory bowel diseases) are multifactorial with poorly understood pathogenesis. Inflammatory bowel diseases are characterized by exacerbated immune responses causing epithelial dysfunction and bacterial translocation. There is no cure and therapies aim at reducing inflammation and restoring intestinal barrier function. Unfortunately, most drugs can have severe side effects. Changes in diet and inclusion of nutritional supplements have been extensively studied in cell culture and animal models, and some supplements have shown promising results in clinical studies. Most of these nutritional supplements including vitamins, fatty acids and phytochemicals reduce oxidative stress and inflammation and have shown beneficial effects during experimental colitis in rodents induced by dextran sulphate sodium or 2,4,6-trinitrobenzene sulfonic acid, which remain the gold standard in pre-clinical colitis research. Here, we summarize the mechanisms through which such nutritional supplements contribute to epithelial barrier stabilization.
Collapse
Affiliation(s)
- Hilda Vargas-Robles
- Department for Molecular Biomedicine, Cinvestav-IPN, Mexico City 07360, Mexico
| | | | | | - Michael Schnoor
- Department for Molecular Biomedicine, Cinvestav-IPN, Mexico City 07360, Mexico
| |
Collapse
|
|
42
|
Chen S, Zhao H, Cheng N, Cao W. Rape bee pollen alleviates dextran sulfate sodium (DSS)-induced colitis by neutralizing IL-1β and regulating the gut microbiota in mice. Food Res Int 2019; 122:241-251. [DOI: 10.1016/j.foodres.2019.04.022] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 04/08/2019] [Accepted: 04/09/2019] [Indexed: 02/08/2023]
|
|
43
|
A Review of the Science of Colorful, Plant-Based Food and Practical Strategies for "Eating the Rainbow". J Nutr Metab 2019; 2019:2125070. [PMID: 33414957 PMCID: PMC7770496 DOI: 10.1155/2019/2125070] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 03/27/2019] [Accepted: 04/17/2019] [Indexed: 01/10/2023] Open
Abstract
Over the past decades, thousands of published studies have amassed supporting recommendations to consume fruits and vegetables for physiological and psychological health. Newer research has emerged to suggest that these plant-based foods contain a plethora of not only vitamins and minerals, but perhaps, most importantly, phytonutrients. These phytonutrients have known pleiotropic effects on cellular structure and function, ultimately resulting in the modulation of protein kinases and subsequent epigenetic modification in a manner that leads to improved outcomes. Even though eating fruits and vegetables is a well-known feature of a healthy dietary pattern, population intakes continue to be below federal recommendations. To encourage consumers to include fruits and vegetables into their diet, an “eat by color” approach is proposed in this review. Although each individual food may have numerous effects based on its constituents, the goal of this simplified approach was to identify general patterns of benefits based on the preponderance of scientific data and known mechanisms of food-based constituents. It is suggested that such a consumer-oriented categorization of these plant-based foods may lead to greater recognition of their importance in the daily diet throughout the lifespan. Other adjunctive strategies to heighten awareness of fruits and vegetables are discussed.
Collapse
|
|
44
|
Li S, Wu B, Fu W, Reddivari L. The Anti-inflammatory Effects of Dietary Anthocyanins against Ulcerative Colitis. Int J Mol Sci 2019; 20:E2588. [PMID: 31137777 PMCID: PMC6567294 DOI: 10.3390/ijms20102588] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 05/21/2019] [Accepted: 05/23/2019] [Indexed: 12/25/2022] Open
Abstract
Ulcerative colitis (UC), which is a major form of inflammatory bowel disease (IBD), is a chronic relapsing disorder of the gastrointestinal tract affecting millions of people worldwide. Alternative natural therapies, including dietary changes, are being investigated to manage or treat UC since current treatment options have serious negative side effects. There is growing evidence from animal studies and human clinical trials that diets rich in anthocyanins, which are pigments in fruits and vegetables, protect against inflammation and increased gut permeability as well as improve colon health through their ability to alter bacterial metabolism and the microbial milieu within the intestines. In this review, the structure and bioactivity of anthocyanins, the role of inflammation and gut bacterial dysbiosis in UC pathogenesis, and their regulation by the dietary anthocyanins are discussed, which suggests the feasibility of dietary strategies for UC mitigation.
Collapse
Affiliation(s)
- Shiyu Li
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA.
| | - Binning Wu
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA.
- Department of Plant Science, Penn State University, University Park, PA 16802, USA.
| | - Wenyi Fu
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA.
| | - Lavanya Reddivari
- Department of Food Science, Purdue University, 745 Agriculture Mall Drive, West Lafayette, IN 47907, USA.
| |
Collapse
|
|
45
|
Xue Y, Du M, Zhu MJ. Raspberry extract prevents NLRP3 inflammasome activation in gut epithelial cells induced by pathogenic Escherichia coli. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
|
|
46
|
Maurer LH, Cazarin CBB, Quatrin A, Minuzzi NM, Costa EL, Morari J, Velloso LA, Leal RF, Rodrigues E, Bochi VC, Júnior MRM, Emanuelli T. Grape peel powder promotes intestinal barrier homeostasis in acute TNBS-colitis: A major role for dietary fiber and fiber-bound polyphenols. Food Res Int 2019; 123:425-439. [PMID: 31284994 DOI: 10.1016/j.foodres.2019.04.068] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 04/28/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases are characterized by impaired intestinal barrier function. This study aimed to evaluate the effects of grape peel powder (GPP) and its bioactive rich-fractions on the barrier function and colonic injury in a model of colitis induced by 2,4,6 trinitrobenzene sulfonic acid (TNBS). Wistar rats received diets supplemented with either GPP (8%), extractable polyphenols (EP), non-extractable polyphenols-rich fraction (NEP-F), or polyphenols-poor, fiber-rich fraction (F) from grapes at amounts equivalent to the GPP group during 15 days before and for 7 days after colitis induction. NEP-F has decreased the extension of colonic lesion but the other grape peel bioactive fractions did not protect against macroscopic or microscopic colonic damage, EP diet increased macroscopic colonic damage. GPP, EP, and NEP-F reduced claudin-2 mRNA expression, whereas GPP and F fraction increased occludin and ZO-1 mRNA expression. All experimental diets reduced the colitis-triggered increase of MMP-9 mRNA expression. Colitis reduced by 30% the production of cecal short-chain fatty acids (SCFA). GPP and NEP-F completely protected against this effect, whereas F fraction was ineffective. Only GPP and NEP-F were able to decrease the upregulation of GRP94 mRNA triggered by colitis. Dietary fiber seems to reestablish the intestinal barrier function, whereas fiber-bound phenolics were able to restore cecal metabolism to produce beneficial metabolites like SCFA and to reduce the activation of the unfolded protein response.
Collapse
Affiliation(s)
- Luana Haselein Maurer
- Graduate Program on Food Science and Technology, Center of Rural Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, Rio Grande do Sul, Brazil; Federal Institute of Education, Science, and Technology Farroupilha, 97555-000 Alegrete, Rio Grande do Sul, Brazil
| | - Cinthia Baú Betim Cazarin
- School of Food Engineering, Department of Food and Nutrition, University of Campinas, Campinas, São Paulo 13083-862, Brazil
| | - Andréia Quatrin
- Federal Institute of Education, Science, and Technology Farroupilha, 97555-000 Alegrete, Rio Grande do Sul, Brazil
| | - Natália Machado Minuzzi
- Integrated Center for Laboratory Analysis Development (NIDAL), Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, Rio Grande do Sul, Brazil
| | - Eduarda Lasch Costa
- Integrated Center for Laboratory Analysis Development (NIDAL), Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, Rio Grande do Sul, Brazil
| | - Joseane Morari
- School of Medical Sciences, Laboratory of Cell Signaling, University of Campinas, Campinas, São Paulo 13084-970, Brazil
| | - Lício Augusto Velloso
- School of Medical Sciences, Laboratory of Cell Signaling, University of Campinas, Campinas, São Paulo 13084-970, Brazil
| | - Raquel Franco Leal
- School of Medical Sciences, Department of Surgery, University of Campinas, Campinas, São Paulo 13083-887, Brazil
| | - Eliseu Rodrigues
- Federal University of Rio Grande do Sul, Institute of Food Science and Technology, 91501-970 Porto Alegre, RS, Brazil
| | - Vivian Caetano Bochi
- Federal University of Health Sciences of Porto Alegre, Department of Nutrition, 90050-170 Porto Alegre, RS, Brazil
| | - Mário Roberto Maróstica Júnior
- School of Food Engineering, Department of Food and Nutrition, University of Campinas, Campinas, São Paulo 13083-862, Brazil
| | - Tatiana Emanuelli
- Graduate Program on Food Science and Technology, Center of Rural Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, Rio Grande do Sul, Brazil; Integrated Center for Laboratory Analysis Development (NIDAL), Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, 97105-900 Santa Maria, Rio Grande do Sul, Brazil.
| |
Collapse
|
|
47
|
Chen Y, Wang JC, Yang CM, Fan Q, Zheng J, Liu H. Positive acceleration adaptive training attenuates gastric ischemia-reperfusion injury through COX-2 and PGE2 expression. Exp Ther Med 2019; 17:2901-2906. [PMID: 30930978 PMCID: PMC6425289 DOI: 10.3892/etm.2019.7288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 03/02/2018] [Indexed: 12/19/2022] Open
Abstract
The mechanism involved in the effects of positive acceleration adaptive training (PAAT) on gastric ischemia-reperfusion injury (GI-RI) has not been fully characterized. The aim of the present study was to investigate the effects of PAAT in attenuating GI-RI in a rat model. The inflammatory factor and caspase-3 levels were measured using ELISA kits. A western blot assay was used to analyze tumor necrosis factor-α (TNF)-α, tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor-related apoptosis inducing ligand (TRAIL), death receptor (DR) 4, DR5, cyclooxygenase (COX)-2, COX-1 and prostaglandin E2 (PGE2) protein expression levels. It was revealed that PAAT could alleviate GI-RI and inflammatory factor levels in a rat model. PAAT suppressed TNF-α and TNFR1 protein expression levels, inhibited TRAIL, DR4, DR5, COX-2 and PGE2 protein expression levels; however, it did not have an effect on COX-1 protein expression in the model of GI-RI. The data indicated that the effects of PAAT attenuated GI-RI through the downregulation of COX-2 and PGE2 expression.
Collapse
Affiliation(s)
- Ying Chen
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| | - Jian-Chang Wang
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| | - Chun-Min Yang
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| | - Qin Fan
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| | - Jun Zheng
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| | - Hao Liu
- Department of Gastroenterology and Research Center of Aeropathy, General Hospital of The Air Force, People's Liberation Army, Beijing 100036, P.R. China
| |
Collapse
|
|
48
|
Yin J, Sheng B, Yang K, Sun L, Xiao W, Yang H. The protective roles of NLRP6 in intestinal epithelial cells. Cell Prolif 2018; 52:e12555. [PMID: 30515917 PMCID: PMC6496424 DOI: 10.1111/cpr.12555] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 10/11/2018] [Accepted: 10/17/2018] [Indexed: 12/12/2022] Open
Abstract
The evolution of chronic inflammatory diseases is thought to be due to a combination of host genetic variations and environmental factors that include the alteration of intestinal flora, termed "dysbiosis." The intestinal mucosal barrier includes a chemical barrier and physical barrier that have important roles in protecting the intestine against inflammatory injury. The chemical barrier includes antimicrobial peptides (AMPs), and the physical barrier includes a mucous layer, a monolayer of intestinal epithelial cells and cell junctions. The intestinal mucosal barrier is not a static barrier, but rather, it strongly interacts with the gut microbiome and cells of the immune system. Correct expression of AMPs, together with mucus and balanced epithelial cell proliferation, prevents the occurrence of disease. NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, participates in the progression of intestinal inflammation and enteric pathogen infections. It has become apparent in recent years that NLRP6 is important in disease pathogenesis, as it responds to internal ligands that lead to the release of AMPs and mucus, thus regulating the regeneration of intestinal epithelial cells. This review summarizes the activation of NLRP6 and its protective role in the intestinal epithelial cell.
Collapse
Affiliation(s)
- Jiuheng Yin
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Baifa Sheng
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Kunqiu Yang
- Department of General Surgery, Navy General Hospital, Beijing, China
| | - Lihua Sun
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Weidong Xiao
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Hua Yang
- Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| |
Collapse
|
|
49
|
Kawabata A, Van Hung T, Nagata Y, Fukuda N, Suzuki T. Citrus kawachiensis Peel Powder Reduces Intestinal Barrier Defects and Inflammation in Colitic Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:10991-10999. [PMID: 30277770 DOI: 10.1021/acs.jafc.8b03511] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
The anti-inflammatory effect of Citrus kawachiensis peel powder was examined in a murine model of dextran sodium sulfate (DSS)-induced colitic mice. In addition to the whole powder, its ethanol extract rich in polyphenolic compounds and ethanol extraction residue rich in dietary fibers were used. The whole powder ameliorated the DSS-induced body weight loss (body weight changes on day 9, Control 108 ± 2, DSS 91 ± 4, DSS+whole peel powder 106 ± 1%, p < 0.05), colon shortening (colon length, Control 5.0 ± 0.1, DSS 3.9 ± 0.1, DSS+whole peel powder 4.7 ± 0.1 cm, p < 0.05), increased expression of pro-inflammatory cytokines (e.g., TNF-α, Control 1.0 ± 0.1, DSS 22.2 ± 5.8, DSS+whole peel powder 4.3 ± 1.5 arbitrary unit, p < 0.05), and decreased expression of colonic tight junctions (TJs) (e.g., occludin, Control 1.00 ± 0.07, DSS 0.21 ± 0.07, DSS+whole peel powder 0.70 ± 0.06 arbitrary unit, p < 0.05). The resolution of abnormalities barring the decreased expression of zonula occludens-2, junctional adhesion molecule-A, and claudin-7 by the extraction residue was comparable to that achieved using the powder (body weight change 107 ± 1%; colon length 4.7 ± 0.1 cm; TNF-α 4.1 ± 0.7; occludin 0.58 ± 0.06 arbitrary unit, p < 0.05). The ethanol extract alone did not have any influence on these abnormalities (body weight change 94 ± 2%; colon length 4.1 ± 0.1 cm; TNF-α 40.5 ± 9.0 arbitrary unit; occludin 0.18 ± 0.02 arbitrary unit, p < 0.05). The powder and ethanol extraction residue, but not ethanol extract, increased fecal acetic acid concentration (Control 4.9 ± 0.6, DSS 5.0 ± 0.9, DSS+whole peel powder 8.8 ± 1.8, DSS+ethanol extract 5.3 ± 0.8, DSS+ethanol extraction residue 12.5 ± 1.1 mmol/L, p < 0.05). Taken together, DFs in the ethanol extraction residue largely contributed to the peel powder-mediated reduction of TJ barrier defect and inflammation in colitic mice.
Collapse
Affiliation(s)
- Ayami Kawabata
- Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , 1-4-4 Kagamiyama , Higashi-Hiroshima 739-8528 , Japan
| | - Tran Van Hung
- Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , 1-4-4 Kagamiyama , Higashi-Hiroshima 739-8528 , Japan
- Ho Chi Minh University of Food Industry , 140 Le Trong Tan, Tay Thanh Ward, Tan Phu District , Ho Chi Minh 700000 , Vietnam
| | - Yoko Nagata
- Food Industrial Technolegy Center , Ehime Institute of Industrial Technology , 487-2, Kume-Kubotamachi , Matsuyama 791-1101 , Japan
| | - Naohiro Fukuda
- Department of Planning and Development , Ehime Institute of Industrial Technology , 487-2, Kume-Kubotamachi , Matsuyama 791-1101 , Japan
| | - Takuya Suzuki
- Department of Biofunctional Science and Technology, Graduate School of Biosphere Science , Hiroshima University , 1-4-4 Kagamiyama , Higashi-Hiroshima 739-8528 , Japan
| |
Collapse
|
|
50
|
Farzaei MH, El-Senduny FF, Momtaz S, Parvizi F, Iranpanah A, Tewari D, Naseri R, Abdolghaffari AH, Rezaei N. An update on dietary consideration in inflammatory bowel disease: anthocyanins and more. Expert Rev Gastroenterol Hepatol 2018; 12:1007-1024. [PMID: 30136591 DOI: 10.1080/17474124.2018.1513322] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder. A wealth of data pointed out that various aspects of chronic inflammation may be affected by several specific dietary factors. This paper calls attention to anthocyanins enriched plant food and anthocyanin dietary supplements, whose role in the management of IBD and its associated oncogenesis deems crucial. Area covered: We updated the most relevant dietary anthocyanins with potential anti-colitis and preventive effect on inflammatory associated colorectal cancer based on the recent animal and human researches along with revealing the major cellular and molecular mechanisms of action. Mounting evidence reported that anthocyanins enriched plant foods perform their protective role on IBD and inflammatory-induced colorectal cancer via different cellular transduction signaling pathways, including inflammatory transcription factors, SAPK/JNK and p38 MAPK cascade, JAK/STAT signaling, NF-kB/pERK/MAPK, Wnt signaling pathway, Nrf2 cytoprotective pathway as well as AMPK pathway and autophagy. Expert commentary: Combination of anthocyanins enriched dietary supplements with existing medications can provide new therapeutic options for IBD patients. Further, well-designed randomized control trials (RCTs) are essential to evaluate the role of anthocyanins enriched medicinal foods as well as isolated anthocyanin components as promising preventive and therapeutic dietary agents for IBD and its associated oncogenesis.
Collapse
Affiliation(s)
- Mohammad Hosein Farzaei
- a Pharmaceutical Sciences Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran
| | - Fardous F El-Senduny
- b Biochemistry division, Chemistry Department , Mansoura University , Mansoura , Egypt
| | - Saeideh Momtaz
- c Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran
- d Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran
| | - Fatemeh Parvizi
- e Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran
| | - Amin Iranpanah
- f Students research Committee, Faculty of Pharmacy , Kermanshah University of Medical Sciences , Kermanshah , Iran
- g PhytoPharmacology Interest Group (PPIG) , Universal Scientific Education and Research Network (USERN) , Kermanshah , Iran
| | - Devesh Tewari
- h Department of Pharmaceutical Sciences, Faculty of Technology, Bhimtal Campus , Kumaun University , Nainital , Uttarakhand , India
| | - Rozita Naseri
- a Pharmaceutical Sciences Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran
| | - Amir Hossein Abdolghaffari
- c Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran
- d Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center , Tehran University of Medical Sciences , Tehran , Iran
- i Department of Pharmacology, Pharmaceutical Sciences Branch , Islamic Azad University , Tehran , Iran
- j Gastrointestinal Pharmacology Interest Group (GPIG) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| | - Nima Rezaei
- k Research Center for Immunodeficiencies, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran
- l Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran
- m Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA) , Universal Scientific Education and Research Network (USERN) , Tehran , Iran
| |
Collapse
|