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Agaricus brasiliensis (sun mushroom) affects the expression of genes related to cholesterol homeostasis

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Abstract

Purpose

The sun mushroom (Agaricus brasiliensis) is considered a major source of bioactive compounds with potential health benefits. Mushrooms typically act as lipid-lowering agents; however, little is known about the mechanisms of action of A. brasiliensis in biological systems. This study aimed to determine the underlying mechanism involved in the cholesterol-lowering effect of A. brasiliensis through the assessment of fecal and serum lipid profiles in addition to gene expression analysis of specific transcription factors, enzymes, and transporters involved in cholesterol homeostasis.

Methods

Twenty-four albino Fischer rats approximately 90 days old, with an average weight of 205 g, were divided into four groups of 6 each and fed a standard AIN-93 M diet (C), hypercholesterolemic diet (H), hypercholesterolemic diet +1 % A. brasiliensis (HAb), or hypercholesterolemic diet +0.008 % simvastatin (HS) for 6 weeks. Simvastatin was used as a positive control, as it is a typical drug prescribed for lipid disorders. Subsequently, blood, liver, and feces samples were collected for lipid profile and quantitative real-time polymerase chain reaction gene expression analyses.

Results

Diet supplementation with A. brasiliensis significantly improved serum lipid profiles, comparable to the effect observed for simvastatin. In addition, A. brasiliensis dietary supplementation markedly promoted fecal cholesterol excretion. Increased expression of 7α-hydroxylase (CYP7A1), ATP-binding cassette subfamily G-transporters (ABCG5/G8), and low-density lipoprotein receptor (LDLR) was observed following A. brasiliensis administration.

Conclusions

Our results suggest that consumption of A. brasiliensis improves the serum lipid profile in hypercholesterolemic rats by modulating the expression of key genes involved in hepatic cholesterol metabolism.

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References

  1. World Health Organization (WHO) (2013) Cardiovascular diseases (CVDs). Geneva, Switzerland. Fact Sheet No. 317, 2013. http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed 15 Jan 2015

  2. Hu X, Wang T, Li W, Jin F, Wang L (2013) Effects of NS Lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet. Lipids Health Dis 12:67

    Article  CAS  Google Scholar 

  3. Nguyen T, Kang JH, Lee MS (2007) Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterol-lowering effects. Int J Food Microbiol 113:358–361

    Article  CAS  Google Scholar 

  4. Gennari JL, Gennari MS, Felipe Jr J, Percário S, Barros IC (2004) Cogumelos medicinais na prevenção e no combate às doenças. In: II International symposium on mushrooms in Brazil, 2004, Brasília, DF. Proceedings. Brasília, 2004, p170–175

  5. Guillamón E, García-Lafuente A, Lozano M, D’Arrigo M, Rostagno MA, Villares A, Martínez JA (2010) Edible mushrooms: role in the prevention of cardiovascular diseases. Fitoterapia 81:715–723

    Article  Google Scholar 

  6. Lakshmi B, Ajith TA, Sheena N, Gunapalan N, Janardhanan KK (2003) Antiperoxidative, anti-inflammatory and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India. Teratog Carcinog Mutagen Suppl 1:85–97

    Article  Google Scholar 

  7. Oliveira OM, Vellosa JC, Fernandes AS, Buffa-Filho W, Hakime-Silva RA, Furlan M, Brunetti IL (2007) Antioxidant activity of Agaricus blazei. Fitoterapia 78:263–264

    Article  CAS  Google Scholar 

  8. Savoie J-M, MinviellE N, Largeteau LM (2008) Radical-scavenging properties of extracts from the white button mushroom, Agaricus bisporus. J Sci Food Agric 88:970–975

    Article  CAS  Google Scholar 

  9. Tsai SY, Tsai HL, Mau JL (2007) Antioxidant properties of Agaricus blazei, Agrocybe cylindracea, and Boletus edulis. LWT Food Sci Technol 40:1392–1402

    Article  CAS  Google Scholar 

  10. Song HH, Chae HS, Oh SR, Lee HK, Chin YW (2012) Anti-inflammatory and anti-allergic effect of Agaricus blazei extract in bone marrow-derived mast cells. Am J Chin Med 40:1073–1084

    Article  CAS  Google Scholar 

  11. Kimura Y, Kido T, Takaku T, Sumiyoshi M, Baba K (2004) Isolation of an anti-angiogenic substance from A. blazei Murill: Its antitumor and antimetastatic actions. Cancer Sci 95:758–764

    Article  CAS  Google Scholar 

  12. Hegele RA (2009) Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet 10:109–121

    Article  CAS  Google Scholar 

  13. Chen J, Zhao H, Ma X, Han X, Luo L, Wang L, Han J, Liu B, Wang W (2012) The effects of jiang-zhi-ning and its main components on cholesterol metabolism. Evid Based Complement Alternat Med 2012:928234

    Google Scholar 

  14. Reena MB, Gowda LR, Lokesh BR (2011) Enhanced hypocholesterolemic effects of interesterified oils are mediated by upregulating LDL receptor and cholesterol 7-α- hydroxylase gene expression in rats. J Nutr 141:24–30

    Article  CAS  Google Scholar 

  15. Brown AJ, Sun L, Feramisco JD, Brown M, Goldstein JL (2002) Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Mol Cell 10:237–245

    Article  CAS  Google Scholar 

  16. Miranda AM, Ribeiro GM, Cunha AC, Silva LS, dos Santos RC, Pedrosa ML, Silva ME (2014) Hypolipidemic effect of the edible mushroom Agaricus blazei in rats subjected to a hypercholesterolemic diet. J Physiol Biochem 70:215–244

    Article  CAS  Google Scholar 

  17. Kerrigan RW (2007) Inclusive and exclusive concepts of Agaricus subrufescens peck: a reply to Wasser. Int J Med Mushrooms 9:79–84

    Article  Google Scholar 

  18. Wasser SP, Didukh MY, de Amazonas MA, Stamets P, da Eira AF (2005) Is a widely cultivated culinary–medicinal royal sun Agaricus (champignon do Brazil, or the Himematsutake mushroom) Agaricus brasiliensis S. Wasser et al. indeed a synonym of A. subrufescens Peck? Int J Med Mushrooms 7:507–511

    Article  Google Scholar 

  19. Wasser SP (2007) Molecular identification of species of the genus Agaricus. Why should we look at morphology? Int J Med Mushrooms 9:85–88

    Article  Google Scholar 

  20. Aira AF, Didukh MY, Stamets PE, Wasser SP, de Amazones MA (2002) Is a widely cultivated culinary-medicinal royal sun Agaricus (the Himematsutake mushroom) indeed Agaricus blazei Murrill? Int J Med Mushrooms 4:267–290

    Google Scholar 

  21. de Siqueira FG, Dias ES, Silva R, da Silva R, Martos ET, Rinker DL (2009) Cultivation of Agaricus blazei ss. Heinemann using different soils as source of casing materials. Sci Agric 66:827–830

    Article  Google Scholar 

  22. Wiliams S (1984) Official methods of analysis of the Association of Official Analytical Chemists. 14th ed. Association of Official Analytical Chemists (AOAC), Arlington

  23. George S, Brat P, Alter P, Amiot MJ (2005) Rapid determination of polyphenols and vitamin C in plants-derived products. J Agric Food Chem 53:1370–1373

    Article  CAS  Google Scholar 

  24. Toor RK, Savage GP (2006) Effect of semi-drying on the antioxidant components of tomatoes. Food Chem 94:90–97

    Article  CAS  Google Scholar 

  25. Brand-Willians W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Techol 28:25–30

    Article  Google Scholar 

  26. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939–1951

    CAS  Google Scholar 

  27. Matos SL, De Paula H, Pedrosa ML, Santos RC, Oliveira EL, Chianca-Júnior DA, Silva ME (2005) Dietary models for inducing hypercholesterolemia in rats. Braz Arch Biol Technol 48:203–209

    Article  CAS  Google Scholar 

  28. Folch J, Lees M, Sloan-Stanley GH (1957) A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    CAS  Google Scholar 

  29. Li G, Liu X, Zhu H, Huang L, Liu Y, Ma C, Qin C (2009) Insulin resistance in insulin-resistant and diabetic hamsters (Mesocricetus auratus) is associated with abnormal hepatic expression of genes involved in lipid and glucose metabolism. Comp Med 59:449–458

    CAS  Google Scholar 

  30. Palou M, Priego T, Sánchez J, Villegas E, Rodríguez AM, Palou A, Picó C (2008) Sequential changes in the expression of genes involved in lipid metabolism in adipose tissue and liver in response to fasting. Pflugers Arch 456:825–836

    Article  CAS  Google Scholar 

  31. Scoggan KA, Gruber H, Chen Q, Plouffe LJ, Lefebvre JM, Wang B, Bertinato J, L’Abbé MR, Hayward S, Ratnayake WM (2009) Increased incorporation of dietary plant sterols and cholesterol correlates with decreased expression of hepatic and intestinal Abcg5 and Abcg8 in diabetic BB rats. J Nutr Biochem 20:177–186

    Article  CAS  Google Scholar 

  32. Shibata S, Hayakawa K, Egashira Y, Sanada H (2007) Roles of nuclear receptors in the up-regulation of hepatic cholesterol 7α-hydroxylase by cholestyramine in rats. Life Sci 80:546–553

    Article  CAS  Google Scholar 

  33. Xiong Q, Xie P, Li H, Hao L, Li G, Qiu T, Liu Y (2010) Acute effects of exposure on the transcription of antioxidant enzyme genes in three organs (liver, kidney, and testis) of male Wistar rats. J Biochem Mol Toxicol 24:361–367

    Article  CAS  Google Scholar 

  34. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2ΔΔCT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  35. Chen ZY, Jiao R, Ma KY (2008) Cholesterol-lowering nutraceuticals and functional foods. J Agric Food Chem 56:8761–8773

    Article  CAS  Google Scholar 

  36. Chavez-Santoscoy RA, Gutierrez-Uribe JA, Granados O, Torre-Villalvazo I, Serna-Saldivar SO, Torres N, Palacios-González B, Tovar AR (2014) Flavonoids and saponins extracted from black bean (Phaseolus vulgaris L.) seed coats modulate lipid metabolism and biliary cholesterol secretion in C57BL/6 mice. Br J Nutr 112:886–899

    Article  CAS  Google Scholar 

  37. Abidi P, Zhou Y, Jiang JD, Liu J (2005) Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler Thromb Vasc Biol 25:2170–2176

    Article  CAS  Google Scholar 

  38. Gunde-Cimerman N, Cimerman A (1995) Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin. Exp Mycol 19:1–6

    Article  CAS  Google Scholar 

  39. Bobek P, Ginter E, Ozdín L (1993) Oyster mushroom (Pleurotus ostreatus) accelerates the plasma clearance of low-density and high-density lipoproteins in rats. Nutr Res 13:885–890

    Article  Google Scholar 

  40. Sugiyama K, Akachi T, Yamakawa A (1995) Hypocholesterolemic action of eritadenine is mediated by a modification of hepatic phospholipid-metabolism in rats. J Nutr 125:2134–2144

    CAS  Google Scholar 

  41. Turkoglu A, Duru ME, Mercan N, Kivrak I, Gezer K (2007) Antioxidant and antimicrobial activities of Laetiporus sulphureus (Bull.) Murrill. Food Chem 101:267–273

    Article  CAS  Google Scholar 

  42. Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS (2008) The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat–fed mice. J Nutr 138:1677–1683

    CAS  Google Scholar 

  43. Naissides M, Mamo JC, James AP, Pal S (2004) The effect of acute red wine polyphenol consumption on post prandial lipaemia in postmenopausal women. Atherosclerosis 177:401–408

    Article  CAS  Google Scholar 

  44. Hardin-Fanning F (2008) The effects of a Mediterranean-style dietary pattern on cardiovascular disease risk. Nurs Clin North Am 43:105–115

    Article  Google Scholar 

  45. Löest HB, Noh SK, Koo SI (2002) Green tea extract inhibits the lymphatic absorption of cholesterol and alpha-tocopherol in ovariectomized rats. J Nutr 132:1282–1288

    Google Scholar 

  46. Raederstorff DG, Schlachter MF, Elste V, Weber P (2003) Effect of EGCG on lipid absorption and plasma lipid levels in rats. J Nutr Biochem 14:326–332

    Article  CAS  Google Scholar 

  47. Fukushima M, Nakano M, Mori Y, Ohashi T, Fujiwara Y, Sonoyama K (2000) Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber. J Nutr 130:2151–2156

    CAS  Google Scholar 

  48. Di Donna L, Iacopetta D, Cappello AR, Galluci G, Martello E, Fiorillo M, Dolce V, Sindona G (2014) Hypocholesterolaemic activity of 3-hydroxy-3-methyl-glutaryl flavanones enriched fraction from bergamot fruit (Citrus bergamia): “In vivo” studies. J Funct Foods 7:558–568

    Article  Google Scholar 

  49. Pullinger CR, Eng C, Salen G, Shefer S, Batta AK, Erickson SK, Verhagen A, Rivera CR, Mulvihill SJ, Malloy MJ, Kane JP (2002) Human cholesterol 7α-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype. J Clin Invest 110:109–117

    Article  CAS  Google Scholar 

  50. Matsui S, Yamane T, Takita T, Oishi Y, Kobayashi-Hattori K (2013) The hypocholesterolemic activity of Momordica charantia fruit is mediated by the altered cholesterol-and bile acid-regulating gene expression in rat liver. Nutr Res 33:580–585

    Article  CAS  Google Scholar 

  51. Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, Hobbs HH (2003) ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem 278:48275–48282

    Article  CAS  Google Scholar 

  52. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ (2002) Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 277:18793–18800

    Article  CAS  Google Scholar 

  53. Cheung PCK (2013) Mini-review on edible mushrooms as source of dietary fiber: preparation and health benefits. Food Sci Hum Wellness 2:162–166

    Article  Google Scholar 

  54. Sato M, Tokuji Y, Yoneyama S, Fujii-Akiyama K, Kinoshita M, Chiji H, Ohnishi M (2013) Effect of dietary Maitake (Grifola frondosa) mushrooms on plasma cholesterol and hepatic gene expression in cholesterol-fed mice. J Oleo Sci 62:1049–1058

    Article  CAS  Google Scholar 

  55. Caz V, Gil-Ramírez A, Largo C, Taberero M, Santamaría M, Martin-Hernández R, Marin FR, Regiero G, Soler-Rivas C (2015) Modulation of cholesterol-related gene expression by dietary fiber fractions from edible mushrooms. J Agric Food Chem 63:7371–7380

    Article  CAS  Google Scholar 

  56. Gil-Ramírez A, Caz V, Martin-Herandez R, Marin FR, Largo C, Rodríguez-Casado A, Tabernero M, Ruiz-Rodriguez A, Regiero G, Soler-Rivas C (2015) Modulation of cholesterol‑related gene expression by ergosterol and ergosterol‑enriched extracts obtained from Agaricus bisporus. Eur J Nutr 1–17

  57. Kim YW, Kim KH, Choi HJ, Lee DS (2005) Anti-diabetic activity of β-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett 27:483–487

    Article  CAS  Google Scholar 

  58. Rideout TC, Fan MZ (2008) Guar gum consumption enhances hepatic ABCG5/G8 expression and increases ileal cholesterol excretion in pigs. FASEB J 22(1092):13

    Google Scholar 

  59. Després JP, Lemieux I, Prud’homme D (2001) Treatment of obesity: need to focus on high risk abdominally obese patients. BMJ 322:716–720

    Article  Google Scholar 

  60. Jung JH, Kim HS (2013) The inhibitory effect of black soybean on hepatic cholesterol accumulation in high cholesterol and high fat diet-induced non-alcoholic fatty liver disease. Food Chem Toxicol 60:404–412

    Article  CAS  Google Scholar 

  61. Tailleux A, Wouters K, Staels B (2012) Roles of PPARs in NAFLD: potential therapeutic targets. Biochim Biophys Acta 1821:809–818

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank the Federal University of Ouro Preto and acknowledge the financial support provided by the following Brazilian government agencies: Foundation for Research Support of the State of Minas Gerais (FAPEMIG), National Council of Scientific and Technological Development (CNPq), and Higher Education Personnel Training Foundation (CAPES/Brazil). The authors thank the Laboratory of Edible Fungi, Federal University of Lavras, Minas Gerais, Brazil, especially Dr. Eustáquio Souza Dias, who kindly provided the mushrooms, which are fundamental to the realization of this work.

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Authors and Affiliations

  1. Research Center in Biological Sciences (NUPEB), Federal University of Ouro Preto, Minas Gerais, Brazil

    Aline Mayrink de Miranda, Joamyr Victor Rossoni Júnior, Lorena Souza e Silva, Marcelo Eustáquio Silva & Maria Lúcia Pedrosa

  2. Department of Foods, School of Nutrition, Federal University of Ouro Preto, Minas Gerais, Brazil

    Rinaldo Cardoso dos Santos & Marcelo Eustáquio Silva

  3. Department of Biological Sciences (DECBI), Federal University of Ouro Preto, Morro do Cruzeiro Campus, Bauxita., Ouro Preto, MG, 35400-000, Brazil

    Maria Lúcia Pedrosa

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  1. Aline Mayrink de Miranda
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  2. Joamyr Victor Rossoni Júnior
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  3. Lorena Souza e Silva
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  4. Rinaldo Cardoso dos Santos
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  5. Marcelo Eustáquio Silva
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  6. Maria Lúcia Pedrosa
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Correspondence to Maria Lúcia Pedrosa.

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de Miranda, A.M., Rossoni Júnior, J.V., Souza e Silva, L. et al. Agaricus brasiliensis (sun mushroom) affects the expression of genes related to cholesterol homeostasis. Eur J Nutr 56, 1707–1717 (2017). https://doi.org/10.1007/s00394-016-1217-x

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