Pelargonidin 3-glucoside-enriched strawberry attenuates symptoms of DSS-induced inflammatory bowel disease and diet-induced metabolic syndrome in rats
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To determine whether the anthocyanin, pelargonidin 3-glucoside (P3G), attenuates symptoms of inflammatory bowel disease (IBD) and metabolic syndrome in rats.
We tested P3G-enriched strawberry in two models of chronic inflammation in rats, chronic IBD induced by 0.5% dextran sodium sulphate in the drinking water for 12 weeks (D) and metabolic syndrome induced by a high-carbohydrate, high-fat diet (H) for 16 weeks. P3G-enriched strawberry was added to the diet for the final 6 weeks in IBD rats (DP) or 8 weeks in H rats (HP) to provide a dose of 8 mg P3G/kg/day.
D rats had marked diarrhoea, bloody stools, erosion of mucosal epithelium, crypt atrophy, loss of villi and goblet cells, and inflammatory cell infiltration. These symptoms were reversed by P3G with healthy stools and mucosal lining of ileum and colon including increased villi, crypts and goblet cells and reduced inflammation. H rats developed hypertension, dyslipidaemia, central obesity, increased ventricular stiffness, cardiac and liver inflammation, and steatosis. P3G treatment in H rats improved systolic blood pressure, ventricular stiffness, and cardiac and liver structure, and reduced abdominal fat, abdominal circumference and body weight gain.
Our study indicates that dietary P3G decreased inflammation to decrease the symptoms of IBD, and to improve cardiovascular, liver and metabolic functions in metabolic syndrome.
KeywordsInflammatory bowel disease Metabolic syndrome Anthocyanin Pelargonidin 3-glucoside Inflammation
Rat urine samples were analysed for sugars at the Central Analytical Research Facility (CARF) of the Queensland University of Technology, Gardens Point, Brisbane, with the assistance of Dr. Rajesh Gupta. Gut histology was performed at the CARF, Queensland University of Technology, Kelvin Grove, Brisbane, with the assistance of Ms Felicity Lawrence. We thank Brian Bynon, School of Veterinary Sciences, The University of Queensland, Gatton, for the plasma analyses. This work was supported by funding received from the University of Southern Queensland Research and Innovation Division.
NKRG, SKP and LB developed the original study aims. NKRG and AS conducted the experiments. NKRG and AS analysed the data whereas NKRG, SKP and LB interpreted the data; NKRG, SKP and LB prepared manuscript drafts and contributed to the final version. LB has been the corresponding author throughout the writing process. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflicts of interest
The authors declare no conflicts of interest.
- 4.Bernstein CN, Fried M, Krabshuis JH, Cohen H, Eliakim R, Fedail S, Gearry R, Goh KL, Hamid S, Khan AG, LeMair AW, Malfertheiner Ouyang Q, Rey JF, Sood A, Steinwurz F, Thomsen OO, Thomson A, Watermeyer G (2010) World Gastroenterology Organization practice guidelines for the diagnosis and management of IBD in 2010. Inflamm Bowel Dis 16(1):112–124. https://doi.org/10.1002/ibd.21048 CrossRefPubMedGoogle Scholar
- 6.Naseri R, Farzaei F, Haratipour P, Nabavi SF, Habtemariam S, Farzaei MH, Khodarahmi R, Tewari D, Momtaz S (2018) Anthocyanins in the management of metabolic syndrome: a pharmacological and biopharmaceutical review. Front Pharmacol 9:1310. https://doi.org/10.3389/fphar.2018.01310 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Afrin S, Gasparrini M, Forbes-Hernandez TY, Reboredo-Rodriguez P, Mezzetti B, Varela-Lopez A, Giampieri F, Battino M (2016) Promising health benefits of the strawberry: a focus on clinical studies. J Agric Food Chem 64(22):4435–4449. https://doi.org/10.1021/acs.jafc.6b00857 CrossRefPubMedGoogle Scholar
- 14.Sodagari HR, Farzaei MH, Bahramsoltani R, Abdolghaffari AH, Mahmoudi M, Rezaei N (2015) Dietary anthocyanins as a complementary medicinal approach for management of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 9(6):807–820. https://doi.org/10.1586/17474124.2015.1002086 CrossRefPubMedGoogle Scholar
- 19.Ichiyanagi T, Kashiwada Y, Shida Y, Sekiya M, Hatano Y, Takaishi Y, Ikeshiro Y (2013) Structural elucidation and biological fate of two glucuronyl metabolites of pelargonidin 3-O-β-d-glucopyranoside in rats. J Agric Food Chem 61(3):569–578. https://doi.org/10.1021/jf3032793 CrossRefPubMedGoogle Scholar
- 22.Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, Kauter K, Sernia C, Campbell F, Ward L, Gobe G, Fenning A, Brown L (2011) High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57(5):611–624. https://doi.org/10.1097/FJC.0b013e31821b1379 CrossRefPubMedGoogle Scholar
- 25.Parlee SD, Lentz SI, Mori H, MacDougald OA (2014) Quantifying size and number of adipocytes in adipose tissue. Methods Enzymol 537:93–122. https://doi.org/10.1016/B978-0-12-411619-1.00006-9s CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Vasina V, Broccoli M, Ursino MG, Canistro D, Valgimigli L, Soleti A, Paolini M, De Ponti F (2010) Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats. World J Gastroenterol 16(29):3642–3650. https://doi.org/10.3748/wjg.v16.i29.3642 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Farzaei MH, Bahramsoltani R, Abdolghaffari AH, Sodagari HR, Esfahani SA, Rezaei N (2016) A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 10(6):745–758. https://doi.org/10.1586/17474124.2016.1145546 CrossRefPubMedGoogle Scholar
- 31.Alipour M, Zaidi D, Valcheva R, Jovel J, Martinez I, Sergi C, Walter J, Mason AL, Wong GK, Dieleman LA, Carroll MW, Huynh HQ, Wine E (2016) Mucosal barrier depletion and loss of bacterial diversity are primary abnormalities in paediatric ulcerative colitis. J Crohns Colitis 10(4):462–471. https://doi.org/10.1093/ecco-jcc/jjv223 CrossRefPubMedGoogle Scholar
- 32.Moran CJ, Walters TD, Guo CH, Kugathasan S, Klein C, Turner D, Wolters VM, Bandsma RH, Mouzaki M, Zachos M, Langer JC, Cutz E, Benseler SM, Roifman CM, Silverberg MS, Griffiths AM, Snapper SB, Muise AM (2013) IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis 19(1):115–123. https://doi.org/10.1002/ibd.22974 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Farzaei MH, El-Senduny FF, Momtaz S, Parvizi F, Iranpanah A, Tewari D, Naseri R, Abdolghaffari AH, Rezaei N (2018) An update on dietary consideration in inflammatory bowel disease: anthocyanins and more. Expert Rev Gastroenterol Hepatol 12(10):1007–1024. https://doi.org/10.1080/17474124.2018.1513322 CrossRefPubMedGoogle Scholar
- 37.Biagioli M, Carino A, Fiorucci C, Annunziato G, Marchiano S, Bordoni M, Roselli R, Giorgio CD, Castiglione F, Ricci P, Bruno A, Faccini A, Distrutti E, Baldoni M, Costantino G, Fiorucci S (2019) The aryl hydrocarbon receptor (AhR) mediates the counter-regulatory effects of pelargonidins in models of inflammation and metabolic dysfunctions. Nutrients 11(8):1820. https://doi.org/10.3390/nu11081820 CrossRefPubMedCentralGoogle Scholar
- 38.Putta S, Yarla NS, Kumar EK, Lakkappa DB, Kamal MA, Scotti L, Scotti MT, Ashraf GM, Barreto GE, Rao BSB, Kumari DS, Reddy GV, Tarasov VV, Imandi SB, Aliev G (2017) Preventive and therapeutic potentials of anthocyanins in diabetes and associated complications. Curr Med Chem 25(39):5347–5371. https://doi.org/10.2174/0929867325666171206101945 CrossRefGoogle Scholar
- 39.Petersen C, Bharat D, Cutler BR, Gholami S, Denetso C, Mueller JE, Cho JM, Kim JS, Symons JD, Anandh Babu PV (2018) Circulating metabolites of strawberry mediate reductions in vascular inflammation and endothelial dysfunction in db/db mice. Int J Cardiol 263:111–117. https://doi.org/10.1016/j.ijcard.2018.04.040 CrossRefPubMedPubMedCentralGoogle Scholar
- 42.Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB (2013) High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 127(2):188–196. https://doi.org/10.1161/CIRCULATIONAHA.112.122408 CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Ellis CL, Edirisinghe I, Kappagoda T, Burton-Freeman B (2011) Attenuation of meal-induced inflammatory and thrombotic responses in overweight men and women after 6-week daily strawberry (Fragaria) intake. A randomized placebo-controlled trial. J Atheroscler Thromb 18(4):318–327. https://doi.org/10.5551/jat.6114 CrossRefPubMedGoogle Scholar
- 44.Aranaz P, Romo-Hualde A, Zabala M, Navarro-Herrera D, Ruiz de Galarreta M, Gil AG, Martinez JA, Milagro FI, Gonzalez-Navarro CJ (2017) Freeze-dried strawberry and blueberry attenuates diet-induced obesity and insulin resistance in rats by inhibiting adipogenesis and lipogenesis. Food Funct 8(11):3999–4013. https://doi.org/10.1039/c7fo00996h CrossRefPubMedGoogle Scholar
- 47.Arjinajarn P, Chueakula N, Pongchaidecha A, Jaikumkao K, Chatsudthipong V, Mahatheeranont S, Norkaew O, Chattipakorn N, Lungkaphin A (2017) Anthocyanin-rich riceberry bran extract attenuates gentamicin-induced hepatotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Biomed Pharmacother 92:412–420. https://doi.org/10.1016/j.biopha.2017.05.100 CrossRefPubMedGoogle Scholar
- 49.Alvarez-Suarez JM, Giampieri F, Tulipani S, Casoli T, Di Stefano G, Gonzalez-Paramas AM, Santos-Buelga C, Busco F, Quiles JL, Cordero MD, Bompadre S, Mezzetti B, Battino M (2014) One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans. J Nutr Biochem 25(3):289–294. https://doi.org/10.1016/j.jnutbio.2013.11.002 CrossRefPubMedGoogle Scholar
- 52.Park E, Edirisinghe I, Wei H, Vijayakumar LP, Banaszewski K, Cappozzo JC, Burton-Freeman B (2016) A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin resistance in a randomized, single-blinded, diet-controlled crossover trial. Mol Nutr Food Res 60(5):1099–1109. https://doi.org/10.1002/mnfr.201500845 CrossRefPubMedGoogle Scholar
- 53.Paquette M, Medina Larque AS, Weisnagel SJ, Desjardins Y, Marois J, Pilon G, Dudonne S, Marette A, Jacques H (2017) Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial. Br J Nutr 117(4):519–531. https://doi.org/10.1017/S0007114517000393 CrossRefPubMedPubMedCentralGoogle Scholar
- 60.Warner EF, Rodriguez-Ramiro I, O’Connell MA, Kay CD (2018) Cardiovascular mechanisms of action of anthocyanins may be associated with the impact of microbial metabolites on heme oxygenase-1 in vascular smooth muscle cells. Molecules 23(4):898. https://doi.org/10.3390/molecules23040898 CrossRefPubMedCentralGoogle Scholar
- 61.Krga I, Tamaian R, Mercier S, Boby C, Monfoulet LE, Glibetic M, Morand C, Milenkovic D (2018) Anthocyanins and their gut metabolites attenuate monocyte adhesion and transendothelial migration through nutrigenomic mechanisms regulating endothelial cell permeability. Free Radic Biol Med 124:364–379. https://doi.org/10.1016/j.freeradbiomed.2018.06.027 CrossRefPubMedGoogle Scholar