Applied Microbiology and Biotechnology

, Volume 91, Issue 3, pp 461–469 | Cite as

Red mold fermented products and Alzheimer's disease: a review

  • Chun-Lin Lee
  • Tzu-Ming PanEmail author


Alzheimer's disease is seen mainly in individuals over the age of 65, and the morbidity rate increases with age. Regarding the health function of Monascus-fermented red mold rice (RMR), besides hypolipidemic and hypotensive effects, other health functions of RMR such as anti-oxidation, cancer prevention, anti-fatigue, and anti-obesity have also been reported. Many published studies have shown the efficacy of RMR in the prevention of Alzheimer's disease. The current article discusses and provides evidence to support the beneficial potential of RMR in the prevention of Alzheimer's disease by discussing the pathogenic factors of Alzheimer's disease and the secondary metabolites of Monascus.


Alzheimer's disease Red mold rice Metabolite 


  1. Akihisa T, Mafune S, Ukiya M, Kimura Y, Yasukawa K, Suzuki T, Tokuda H, Tanabe N, Fukuoka T (2004) (+)- and (−)-syn-2-isobutyl-4-methylazetidine −2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (red-mold rice). J Nat Prod 67:479–480CrossRefGoogle Scholar
  2. Akihisa T, Tokuda H, Yasukawa K, Ukiya M, Kiyota A, Sakamoto N, Suzuki T, Tanabe N, Nishino H (2005) Azaphilones, furanoisophthalides, and amino acids from the extracts of Monascus pilosus-fermented rice (red-mold rice) and their chemopreventive effects. J Agric Food Chem 53:562–565CrossRefGoogle Scholar
  3. Andrews-Zwilling Y, Bien-Ly N, Xu Q, Li G, Bernardo A, Yoon SY, Zwilling D, Yan TX, Chen L, Huang Y (2010) Apolipoprotein E4 causes age- and tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J Neurosci 30:13707–13717CrossRefGoogle Scholar
  4. Aniya Y, Ohtani II, Higa T, Miyagi C, Gibo H, Shimabukuro M, Nakanishi H, Taira J (2000) Dimerumic acid as an antioxidant of the mold, Monascus anka. Free Radic Biol Med 28:999–1004CrossRefGoogle Scholar
  5. Araki W, Kitaguchi N, Tokushima Y, Ishii Y, Aratake K, Shimohama H, Nakamura S, Kimura J (1991) Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181:265–271CrossRefGoogle Scholar
  6. Buxbaum JD, Thinakaran G, Koliatsos V, O'Callahan J, Slunt HH, Price DL, Sisodia SS (1998) Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path. J Neurosci 18:9629–9637Google Scholar
  7. Checler F (1995) Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease. J Neurochem 65:1431–1444CrossRefGoogle Scholar
  8. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE (2000) Inflammatory mechanisms in Alzheimer's disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists. J Neurosci 20:558–567Google Scholar
  9. Cordle A, Koenigsknecht-Talboo J, Wilkinson B, Limpert A, Landreth G (2005) Mechanisms of statin-mediated inhibition of small G-protein function. J Biol Chem 280:34202–34209CrossRefGoogle Scholar
  10. Cordle A, Landreth G (2005) 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors attenuate beta-amyloid-induced microglial inflammatory responses. J Neurosci 25:299–307CrossRefGoogle Scholar
  11. Crisby M, Carlson LA, Winblad B (2002) Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord 16:131–136CrossRefGoogle Scholar
  12. Endo A (1979) Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. The Journal of Antibiot (Tokyo) 32:852–854Google Scholar
  13. Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T (2006) Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 399:91–95CrossRefGoogle Scholar
  14. Fassbender K, Stroick M, Bertsch T, Ragoschke A, Kuehl S, Walter S, Walter J, Brechtel K, Muehlhauser F, Von Bergmann K, Lutjohann D (2002) Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology 59:1257–1258Google Scholar
  15. Frears ER, Stephens DJ, Walters CE, Davies H, Austen BM (1999) The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 10:1699–1705CrossRefGoogle Scholar
  16. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63:1402–1408CrossRefGoogle Scholar
  17. Ghribi O, Larsen B, Schrag M, Herman MM (2006) High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol 200:460–467CrossRefGoogle Scholar
  18. Giacobini E, Mori F, Lai CC (1996) The effect of cholinesterase inhibitors on the secretion of APPS from rat brain cortex. Ann N Y Acad Sci 777:393–398CrossRefGoogle Scholar
  19. Hashimoto M, Hossain S, Agdul H, Shido O (2005) Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions. Biochim Biophys Acta 1738:91–98Google Scholar
  20. Hauss-Wegrzyniak B, Dobrzanski P, Stoehr JD, Wenk GL (1998) Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease. Brain Res 780:294–303CrossRefGoogle Scholar
  21. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356:1627–1631CrossRefGoogle Scholar
  22. Juzlova PM, Martinkova L, Kren V (1996) Secondary metabolites of the fungus Monascus: a review. J Ind Microbiol 16:163–170CrossRefGoogle Scholar
  23. Kirsch C, Eckert GP, Mueller WE (2003) Statin effects on cholesterol micro-domains in brain plasma membranes. Biochem Pharmacol 65:843–856CrossRefGoogle Scholar
  24. Kuo YM, Emmerling MR, Bisgaier CL, Essenburg AD, Lampert HC, Drumm D, Roher AE (1998) Elevated low-density lipoprotein in Alzheimer's disease correlates with brain abeta 1–42 levels. Biochem Biophys Res Commun 252:711–715CrossRefGoogle Scholar
  25. Lee CL, Kuo TF, Wang JJ, Pan TM (2007) Red mold rice ameliorates impairment of memory and learning ability in intracerebroventricular amyloid beta-infused rat by repressing amyloid beta accumulation. J Neurosci Res 85:3171–3182CrossRefGoogle Scholar
  26. Lee CL, Kuo TF, Wu CL, Wang JJ, Pan TM (2010) Red mold rice promotes neuroprotective sAPPalpha secretion instead of Alzheimer's risk factors and amyloid beta expression in hyperlipidemic Abeta40-infused rats. J Agric Food Chem 58:2230–2238CrossRefGoogle Scholar
  27. Lee CL, Tsai TY, Wang JJ, Pan TM (2006a) In vivo hypolipidemic effects and safety of low dosage Monascus powder in a hamster model of hyperlipidemia. Appl Microbiol Biotechnol 70:533–540CrossRefGoogle Scholar
  28. Lee CL, Wang JJ, Pan TM (2008) Red mold rice extract represses amyloid beta peptide-induced neurotoxicity via potent synergism of anti-inflammatory and antioxidative effect. Appl Microbiol Biotechnol 79:829–841CrossRefGoogle Scholar
  29. Lee CL, Wang JJ, Kuo SL, Pan TM (2006b) Monascus fermentation of dioscorea for increasing the production of cholesterol-lowering agent-monacolin K and antiinflammation agent-monascin. Appl Microbiol Biotechnol 72:1254–1262CrossRefGoogle Scholar
  30. Li L, Cao D, Kim H, Lester R, Fukuchi K (2006) Simvastatin enhances learning and memory independent of amyloid load in mice. Ann Neurol 60:729–739CrossRefGoogle Scholar
  31. Liao JK (2002) Isoprenoids as mediators of the biological effects of statins. J Clin Invest 110:285–288Google Scholar
  32. Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118CrossRefGoogle Scholar
  33. Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, Zhang D, Cooper R, Chang M (2000) Constituents of red yeast rice, a traditional Chinese food and medicine. J Agric Food Chem 48:5220–5225CrossRefGoogle Scholar
  34. Mackenzie IR, Munoz DG (1998) Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology 50:986–990Google Scholar
  35. Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Kohsaka S (1998) Involvement of amyloid precursor protein in functional synapse formation in cultured hippocampal neurons. J Neurosci Res 51:185–195CrossRefGoogle Scholar
  36. Naidu A, Xu Q, Catalano R, Cordell B (2002) Secretion of apolipoprotein E by brain glia requires protein prenylation and is suppressed by statins. Brain Res 958:100–111CrossRefGoogle Scholar
  37. Perez‐Severiano F, Rodriguez‐Perez M, Pedraza‐Chaverri J, Maldonado PD, Medina‐Campos ON, Ortiz‐Plata A, Sanchez‐Garcia A, Villeda‐Hernandez J, Galvan‐Arzate S, Aguilera P, Santamaria A (2004) S‐Allylcysteine, a garlic‐derived antioxidant, ameliorates quinolinic acid‐induced neurotoxicity and oxidative damage in rats. Neurochem Int 45:1175–1183Google Scholar
  38. Poirier J (2003) Apolipoprotein E and cholesterol metabolism in the pathogenesis and treatment of Alzheimer's disease. Trends Mol Med 9:94–101CrossRefGoogle Scholar
  39. Pollen DA, Baker S, Hinerfeld D, Swearer J, Evans BA, Evans JE, Caselli R, Rogaeva E, St George-Hyslop P, Moonis M (2010) Prevention of Alzheimer's disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E epsilon 4. Alzheimers Res Ther 2:31CrossRefGoogle Scholar
  40. Rockwood K, Kirkland S, Hogan DB, MacKnight C, Merry H, Verreault R, Wolfson C, McDowell I (2002) Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 59:223–227CrossRefGoogle Scholar
  41. Roher AE, Kuo YM (1999) Isolation of amyloid deposits from brain. Methods Enzymol 309:58–67CrossRefGoogle Scholar
  42. Sastre M, Klockgether T, Heneka MT (2006) Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms. Int J Dev Neurosci 24:167–176CrossRefGoogle Scholar
  43. Schubert D, Behl C (1993) The expression of amyloid beta protein precursor protects nerve cells from beta-amyloid and glutamate toxicity and alters their interaction with the extracellular matrix. Brain Res 629:275–282CrossRefGoogle Scholar
  44. Schubert D, Behl C, Lesley R, Brack A, Dargusch R, Sagara Y, Kimura H (1995) Amyloid peptides are toxic via a common oxidative mechanism. Proc Natl Acad Sci USA 92:1989–1993CrossRefGoogle Scholar
  45. Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, Masters CL (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 14:2117–2127Google Scholar
  46. Stewart R (1998) Cardiovascular factors in Alzheimer's disease. J Neurol Neurosurg Psychiatry 65:143–147CrossRefGoogle Scholar
  47. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90:1977–1981CrossRefGoogle Scholar
  48. Su YC, Wang JJ, Lin TT, Pan TM (2003) Production of the secondary metabolites gamma-amino butyric acid and monacolin K by Monascus. J Ind Microbiol Biotechnol 30:41–46Google Scholar
  49. Tang F, Nag S, Shiu SY, Pang SF (2002) The effects of melatonin and Ginkgo biloba extract on memory loss and choline acetyltransferase activities in the brain of rats infused intracerebroventricularly with beta-amyloid 1–40. Life Sci 71:2625–2631CrossRefGoogle Scholar
  50. Townsend KP, Pratico D (2005) Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J 19:1592–1601CrossRefGoogle Scholar
  51. Wang R, Zhang HY, Tang XC (2001) Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1–40) in rat. Eur J Pharmacol 421:149–156CrossRefGoogle Scholar
  52. Wolozin B, Kellman W, Ruosseau P, Celesia GG, Siegel G (2000) Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 57:1439–1443CrossRefGoogle Scholar
  53. Wong HC, Bau YS (1977) Pigmentation and antibacterial activity of fast neutron- and x-ray-induced strains of Monascus purpureus Went. Plant Physiol 60:578–581CrossRefGoogle Scholar
  54. Yamada K, Ren X, Nabeshima T (1999) Perspectives of pharmacotherapy in Alzheimer’s disease. Jpn J Pharmacol 80:9–14Google Scholar
  55. Yamaguchi Y, Miyashita H, Tsunekawa H, Mouri A, Kim HC, Saito K, Matsuno T, Kawashima S, Nabeshima T (2006) Effects of a novel cognitive enhancer, spiro[imidazo‐[1,2‐a]pyridine‐3,2‐indan]‐2(3H)‐one (ZSET1446), on learning impairments induced by amyloid‐beta1‐40 in the rat. J Pharmacol Exp Ther 317:1079–1087Google Scholar
  56. Zhao B (2005) Natural antioxidants for neurodegenerative diseases. Mol Neurobiol 31:283–293CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Life ScienceNational Taitung UniversityTaitungTaiwan, ROC
  2. 2.Department of Biochemical Science and Technology, College of Life ScienceNational Taiwan UniversityTaipeiTaiwan, ROC

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