Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Development of an Improved Menopausal Symptom-Alleviating Licorice (Glycyrrhiza uralensis) by Biotransformation Using Monascus albidulus

  • Kim, Kang Uk (Department of Bio and Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University) ;
  • Lee, Sung-Jin (Food R&D Center, SK Bioland Co., Ltd.) ;
  • Lee, Inhyung (Department of Bio and Fermentation Convergence Technology, BK21 PLUS Project, Kookmin University)
  • Received : 2019.09.20
  • Accepted : 2019.11.18
  • Published : 2020.02.28
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Abstract

Licorice (Glycyrrhiza uralensis) contains several compounds that have been reported to alleviate menopausal symptoms via interacting with estrogen receptors (ERs). The compounds exist mainly in the form of glycosides, which exhibit low bioavailability and function. To bioconvert liquiritin and isoliquiritin, the major estrogenic compounds, to the corresponding deglycosylated liquiritigenin and isoliquiritigenin, respectively, licorice was fermented with Monascus, which has been demonstrated to deglycosylate other substances. The contents of liquiritigenin and isoliquiritigenin in Monascus-fermented licorice increased by 10.46-fold (from 38.03 μM to 379.75 μM) and 12.50-fold (from 5.53 μM to 69.14 μM), respectively, compared with their contents in non-fermented licorice. Monascus-fermented licorice exhibited 82.5% of the ERβ binding activity of that observed in the positive control (17 β-estradiol), whereas the non-fermented licorice exhibited 54.1% of the binding activity in an in vivo ER binding assay. The increase in the ERβ binding activity was associated with increases in liquiritigenin and isoliquiritigenin contents. Liquiritigenin acts as a selective ligand for ERβ, which alleviates menopausal symptoms with fewer side effects, such as heart disease and hypertension, compared with a ligand for ERα. In addition, Monascus-fermented licorice contained 731 mg/kg of monacolin K, one of the metabolites produced by Monascus that reduces serum cholesterol. Therefore, Monascus-fermented licorice is a promising material for the prevention and treatment of menopausal syndrome with fewer side effects.

Keywords

References

  1. Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. 2001. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 61: 5045-5050.
  2. Aura A-M. 2008. Microbial metabolism of dietary phenolic compounds in the colon. Phytochem. Rev. 7: 407-429. https://doi.org/10.1007/s11101-008-9095-3
  3. Avis NE, Stellato R, Crawford S, Bromberger J, Ganz P, Cain V, et al. 2001. Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic groups. Soc. Sci. Med. 52: 345-356. https://doi.org/10.1016/S0277-9536(00)00147-7
  4. Blanc PJ, Laussac J, Le Bars J, Le Bars P, Loret M, Pareilleux A, et al. 1995. Characterization of monascidin A from Monascus as citrinin. Int. J. Food Microbiol. 27: 201-213. https://doi.org/10.1016/0168-1605(94)00167-5
  5. Boonmuen N, Gong P, Ali Z, Chittiboyina AG, Khan I, Doerge DR, et al. 2016. Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities. Steroids 105: 42-49. https://doi.org/10.1016/j.steroids.2015.11.006
  6. De Boever P, Demare W, Vanderperren E, Cooreman K, Bossier P, Verstraete W. 2001. Optimization of a yeast estrogen screen and its applicability to study the release of estrogenic isoflavones from a soygerm powder. Environ. Health Perspect. 109: 691-697. https://doi.org/10.1289/ehp.01109691
  7. Depypere HT, Comhaire FH. 2014. Herbal preparations for the menopause: beyond isoflavones and black cohosh. Maturitas 77: 191-194. https://doi.org/10.1016/j.maturitas.2013.11.001
  8. Endo A. 1979. Monacolin K, a new hypocholesteroemic agent produced by a Monascus species. J. Antibiot. (Tokyo). 32: 852-854. https://doi.org/10.7164/antibiotics.32.852
  9. Erdogrul L. 2004. Review of the studies on the red yeast rice (Monascus purpureus). Turkish Electro. J. Biotechnol. 2: 37-49.
  10. Ettinger B. 1998. Overview of estrogen replacement therapy: a historical perspective. Proc. Soc. Exp. Biol. Med. 217: 2-5. https://doi.org/10.3181/00379727-217-44198
  11. Fox JE, Burow ME, McLachlan JA, Miller III CA. 2008. Detecting ligands and dissecting nuclear receptor-signaling pathways using recombinant strains of the yeast Saccharomyces cerevisiae. Nat. Protoc. 3: 637-645. https://doi.org/10.1038/nprot.2008.33
  12. Gong P, Madak-Erdogan Z, Li J, Cheng J, Greenlief CM, Helferich W, et al. 2014. Transcriptomic analysis identifies gene networks regulated by estrogen receptor $\alpha$ ( $ER{\alpha}$) and $ER{\beta}$ that control distinct effects of different botanical estrogens. Nucl. Recept. Signal. 12: e001.
  13. Hankinson SE, Eliassen AH. 2007. Endogenous estrogen, testosterone and progesterone levels in relation to breast cancer risk. J. Steroid Biochem. Mol. Biol. 106: 24-30. https://doi.org/10.1016/j.jsbmb.2007.05.012
  14. Hong S-Y, Oh J-H, Lee I. 2011. Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in red ginseng by fermentation with Monascus pilosus. Biosci. Biotechnol. Biochem. 75: 1490-1495. https://doi.org/10.1271/bbb.110195
  15. Hsieh C-Y, Santell RC, Haslam SZ, Helferich WG. 1998. Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58: 3833-3838.
  16. Hwang HJ, Jeong SC, Park JP. 2015. Production of liquiritigenin with cell-based biotrasformation and its antiaging activity. Kor. Soc. Biotechnol. Bioeng. J. 30: 166-174.
  17. Writing Groups for the Women's Health Initiative Investigators. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288: 321-333. https://doi.org/10.1001/jama.288.3.321
  18. Kao T-C, Wu C-H, Yen G-C. 2014. Bioactivity and potential helth benefits of licorice. J. Agric. Food Chem. 62: 542-553. https://doi.org/10.1021/jf404939f
  19. Kim H-J, Ji GE, Lee I. 2007. Natural occuring levels of citrinin and monacolin K in Korean Monascus fermentation products. Food Sci. Biotechnol. 16: 142-145.
  20. Kim JY, Kim H-J, Oh J-H, Lee I. 2010. Characteristics of Monascus sp. isolated from Monascus fermentation products. Food Sci. Biotechnol. 19: 1151-1157. https://doi.org/10.1007/s10068-010-0164-1
  21. Kondo K, Shiba M, Nakamura R, Morota T, Shoyama Y. 2007. Constituent properties of licorices derived from Glycyrrhiza uralensis, G. glabra, or G. inflata identified by genetic information. Biol. Pharm. Bull. 30: 1271-1277. https://doi.org/10.1248/bpb.30.1271
  22. Krejci ME, Bretz NS, Koechel DA. 1996. Citrinin produces acute adverse changes in renal function and ultrastructure in pentobarbital-anesthetized dogs without concomitant reductions in [potassium] plasma. Toxicology 106: 167-177. https://doi.org/10.1016/0300-483X(95)03183-G
  23. Kuba-Miyara M, Yasuda M. 2012. Bioorganic compounds produced by the fungus Monascus and their use in health sciences ans medicine. Mini-Rev. Org. Chem. 9: 11-19. https://doi.org/10.2174/157019312799080071
  24. Lee DS, Lee I. 2012. Development of monacolin K-enriched ganghwayakssuk (Artemisia princeps Pamp.) by fermentation with Monascus pilosus. J. Microbiol. Biotechnol. 22: 975-980. https://doi.org/10.4014/jmb.1201.01016
  25. Lim JY, Kim JJ, Lee DS, Kim GH, Shim JY, Lee I, Imm JY. 2010. Physicochemical characteristics and production of whole soymilk from Monascus fermented soybeans. Food Chem. 120: 255-260. https://doi.org/10.1016/j.foodchem.2009.10.017
  26. Lin YL. 2008. Biologically active components and nutraceuticals in the Monascus-fermented rice: a review. Appl. Microbiol. Biotechnol. 77: 965-973. https://doi.org/10.1007/s00253-007-1256-6
  27. Lo R, Matthews J. 2010. A new class of estrogen receptor beta-selective activators. Mol. Interv. 10: 133-136. https://doi.org/10.1124/mi.10.3.3
  28. Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, et al. 2000. Constituents of red yeast rice, a traditional Chinese food and medicine. J. Agric. Food Chem. 48: 5220-5225. https://doi.org/10.1021/jf000338c
  29. Mazur W, Adlercreutz H. 2000. Overview of naturally occuringendocrine-active substances in the human diet in relation to human health. Nutrition 16: 654-687. https://doi.org/10.1016/S0899-9007(00)00333-6
  30. Mersereau JE, Levy N, Staub RE, Baggett LF, Leitman DC. 2008. Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol. Cell. Endocrinol. 283: 49-57. https://doi.org/10.1016/j.mce.2007.11.020
  31. Miller III CA, Tan X, Wilson M, Bhattacharyya S, Ludwig S. 2010. Single plasmids expressing human steroid hormone receptors and a reporter gene for use in yeast signaling assays. Plasmid 63: 73-78. https://doi.org/10.1016/j.plasmid.2009.11.003
  32. Nilsson S, Koehler KF, Gustafsson JA. 2011. Development of subtype-selective oestrogen receptor-based therapeutics. Nat. Rev. Drug Discov. 10: 778-792. https://doi.org/10.1038/nrd3551
  33. Oldenhave A, Jaszmann LJ, Haspels AA, Everaerd WTA. 1993. Impact of climacteric on well-being: a survey based on 5213 women 39 to 60 years old. Am. J. Obstet. Gynecol. 168: 772-780. https://doi.org/10.1016/s0002-9378(12)90817-0
  34. Paruthiyil S, Cvoro A, Zhao X, Wu Z, Sui Y, Staub RE, et al. 2009. Drug and cell type-specific regulation of genes with different classes of estrogen receptor $\beta$-selective agonists. PLoS One 4: e6271. https://doi.org/10.1371/journal.pone.0006271
  35. Pisareva E, Savov V, Kujumdzieva A. 2005. Pigments and citrinin biosynthesis by fungi belonging to genus Monascus. Z. Naturforsch. C J. Biosci. 60: 116-120. https://doi.org/10.1515/znc-2005-1-221
  36. Roepke TA, Ronnekleiv OK, Kelly MJ. 2011. Physiological consequences of membrane-initiated estrogen signaling in the brain. Front. Biosci. 16: 1560-1573. https://doi.org/10.2741/3805
  37. Sato Y, He J-X, Nagai H, Tani T, Akao T. 2007. Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis roots, acts in the lower part of intestine. Biol. Pharm. Bull. 30: 145-149. https://doi.org/10.1248/bpb.30.145
  38. Simmler C, Hajirahimkhan A, Lankin DC, Bolton JL, Jones T, Soejarto DD, et al. 2013. Dynamic residual complexity of the isoliquiritigenin-liquiritigenin interconversion during bioassay. J. Agric. Food Chem. 61: 2146-2157. https://doi.org/10.1021/jf304445p
  39. Song J, Luo J, Ma Z, Sun Q, Wu C-H, Li X. 2019. Quality and authenticity conttrol of functional red yeast rice- a review. Molecules 24(10). pii: E19.
  40. Song W, Qiao X, Chen K, Wang Y, Ji S, Feng J, et al. 2017. Biosynthesis-based quantitative analysis of 151 secondary metabolites of licorice to differentiate medicinal Glycyrrhiza species and their hybrids. Anal. Chem. 89: 3146-3153. https://doi.org/10.1021/acs.analchem.6b04919
  41. Su Y-C, Wang J-J, Lin T-T, Pan T-M. 2003. Production of the secondary metabolites $\gamma$-aminobutyric acid and monacolin K by Monascus. J. Ind. Microbiol. Biotechnol. 30: 41-46. https://doi.org/10.1007/s10295-002-0001-5
  42. Tamir S, Eizenberg M, Somjen D, Izrael S, Vaya J. 2001. Estrogen-like activity of glabrene and other constituents isolated from licorice root. J. Steroid Biochem. Mol. Biol. 78: 291-298. https://doi.org/10.1016/S0960-0760(01)00093-0
  43. van Patten CL, Olivotto IA, Chambers GK, Gelmon KA, Hislop TG, Templeton E, et al. 2002. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J. Clin. Oncol. 20: 1449-1455. https://doi.org/10.1200/JCO.20.6.1449
  44. Wang ZY, Nixon DW. 2001. Licorice and cancer. Nutr. Cancer. 39: 1-11. https://doi.org/10.1207/S15327914nc391_1
  45. Zhang W, Jiang S, Qian D, Shang Ex, Duan Ja. 2014. Effect of liquiritin on human intestinal bacteria growth: metabolism and modulation. Biomed. Chromatogr. 28: 1271-1277. https://doi.org/10.1002/bmc.3160