Skip to main content

Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase inhibition


Mulberroside A, a glycosylated stilbene, was isolated and identified from the ethanol extract of the roots of Morus alba. Oxyresveratrol, the aglycone of mulberroside A, was produced by enzymatic hydrolysis of mulberroside A using the commercial enzyme Pectinex®. Mulberroside A and oxyresveratrol showed inhibitory activity against mushroom tyrosinase with an IC50 of 53.6 and 0.49 μM, respectively. The tyrosinase inhibitory activity of oxyresveratrol was thus approximately 110-fold higher than that of mulberroside A. Inhibition kinetics showed mulberroside A to be a competitive inhibitor of mushroom tyrosinase with l-tyrosine and l-DOPA as substrate. Oxyresveratrol showed mixed inhibition and noncompetitive inhibition against l-tyrosine and l-DOPA, respectively, as substrate. The results indicate that the tyrosinase inhibitory activity of mulberroside A was greatly enhanced by the bioconversion process.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. Andrabi SA, Spina MG, Lorenz P, Ebmeyer U, Wolf G, Horn TF (2004) Oxyresveratrol (trans-2, 3′, 4, 5′-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. Brain Res 1017:98–107

    Article  CAS  PubMed  Google Scholar 

  2. Bajpai VK, Kim HR, Hou CT, Kang SC (2009) Bioconverted products of essential fatty acids as potential antimicrobial agents. N Biotechnol 26:122–130

    Article  CAS  PubMed  Google Scholar 

  3. Chen JS, Wei C, Rolle RS, Otwell WS, Balaban MO, Marshall MR (1991) Inhibitory effect of kojic acid on some plant and crustacean polyphenol oxidases. J Agric Food Chem 39:1396–1401

    Article  CAS  Google Scholar 

  4. Choi SY, Kim S, Kim H, Suk K, Hwang JS, Lee BG, Kim AJ, Kim SY (2002) (4-Methoxy-benzylidene)-(3-methoxy-phenyl)-amine, a nitrogen analog of stilbene as a potent inhibitor of melanin production. Chem Pharm Bull 50:450–452

    Article  CAS  PubMed  Google Scholar 

  5. Chung KO, Kim BY, Lee MH, Kim YR, Chung HY, Park JH, Moon JO (2003) In vitro and in vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol 55:1695–1700

    Article  CAS  PubMed  Google Scholar 

  6. El-Beshbishy HA, Singab ANB, Sinkkonen J, Pihlaja K (2006) Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats. Life Sci 78:2724–2733

    Article  CAS  PubMed  Google Scholar 

  7. Feng X, Zhang L, Zhu H (2009) Comparative anticancer and antioxidant activities of different ingredients of Ginkgo biloba extract (EGb 761). Planta Med 75:792–796

    Article  CAS  PubMed  Google Scholar 

  8. Habauzit V, Nielsen IL, Gil-Izquierdo A, Trzeciakiewicz A, Morand C, Chee W, Barron D, Lebecque P, Davicco MJ, Williamson G, Offord E, Coxam V, Horcajada MN (2009) Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats. Br J Nutr 102:976–984

    Article  CAS  PubMed  Google Scholar 

  9. Hirakura K, Fujimoto Y, Fukai T, Nomura T (1986) Two phenolic glycosides from the root bark of the cultivated Mulberry tree (Morus lhou). J Nat Prod 49:218–224

    Article  CAS  Google Scholar 

  10. Kim DH, Kim JH, Baek SH, Seo JH, Kho YH, Oh TK, Lee CH (2004) Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase. Biotechnol Bioeng 87:849–854

    Article  CAS  PubMed  Google Scholar 

  11. Kim YM, Yun J, Lee CK, Lee H, Min KR, Kim Y (2002) Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J Biol Chem 277:16340–16344

    Article  CAS  PubMed  Google Scholar 

  12. Körner AM, Pawelek J (1982) Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science 217:1163–1165

    Article  PubMed  Google Scholar 

  13. Kubo I, Hori IK (1999) Flavonols from Saffron flower: tyrosinase inhibitory activity and inhibition mechanism. J Agric Food Chem 47:4121–4125

    Article  CAS  PubMed  Google Scholar 

  14. Li H, Cheng KW, Cho CH, He Z, Wang M (2007) Oxyresveratrol as an antibrowning agent cloudy apple juices and fresh-cut apples. J Agric Food Chem 55:2604–2610

    Article  CAS  PubMed  Google Scholar 

  15. Liederer BM, Borchardt RT (2006) Enzymes involved in the bioconversion of ester-based prodrugs. J Pharm Sci 95:1177–1195

    Article  CAS  PubMed  Google Scholar 

  16. Likhitwitayawuid K, Sornsute A, Sritularak B, Ploypradith P (2006) Chemical transformations of oxyresveratrol (trans-2, 4, 3′, 5′-tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent. Bioorg Med Chem Lett 16:5650–5653

    Article  CAS  PubMed  Google Scholar 

  17. Lorenz P, Roychowdhury S, Engelmann M, Wolf G, Horn TF (2003) Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 9:64–76

    Article  CAS  PubMed  Google Scholar 

  18. Marotti I, Bonetti A, Biavati B, Catizone P, Dinelli G (2007) Biotransformation of common bean (Phaseolus vulgaris L.) flavonoid glycosides by bifidobacterium species from human intestinal origin. J Agric Food Chem 55:3913–3919

    Article  CAS  PubMed  Google Scholar 

  19. Mayer AM (1987) Polyphenol oxidases in plants: recent progress. Phytochemistry 26:11–20

    Article  Google Scholar 

  20. Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, Ogawa S, Inoue S, Muramatsu M, Masamune Y (2001) Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol Pharm Bull 24:351–356

    Article  CAS  PubMed  Google Scholar 

  21. Nielsen IL, Chee WS, Poulsen L, Offord-Cavin E, Rasmussen SE, Frederiksen H, Enslen M, Barron D, Horcajada MN, Williamson G (2006) Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial. J Nutr 136:404–408

    CAS  PubMed  Google Scholar 

  22. Otieno DO, Shah NP (2007) A comparison of changes in the transformation of isoflavones in soymilk using varying concentrations of exogenous and probiotic-derived endogenous β-glucosidases. J Appl Microbiol 103:601–612

    Article  CAS  PubMed  Google Scholar 

  23. Pereira JA, Pereira AP, Ferreira IC, Valentão P, Andrade PB, Seabra R, Estevinho L, Bento A (2006) Table olives from Portugal: phenolic compounds, antioxidant potential, and antimicrobial activity. J Agric Food Chem 54:8425–8431

    Article  CAS  PubMed  Google Scholar 

  24. Qiu F, Komatsu K, Kawasaki K, Saito K, Yao X, Kano Y (1996) A novel stilbene glycoside, oxyresveratrol 3′-O-β-glucopyranoside, from the root bark of Morus alba. Planta Med 62:559–561

    Article  CAS  PubMed  Google Scholar 

  25. Rooseboom M, Commandeur JN, Vermeulen NP (2004) Enzyme-catalyzed activation of anticancer prodrugs. Parmacol Rev 56:53–102

    CAS  Google Scholar 

  26. Ryu SY, Han YN, Han BH (1988) Monoamine oxidase-A inhibitors from medicinal plants. Arch Pharm Res 11:230–239

    Article  CAS  Google Scholar 

  27. Schweikardt T, Olivares C, Solano F, Jaenicke E, García-Borrón JC, Decker H (2007) A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations. Pigment Cell Res 20:394–401

    CAS  PubMed  Google Scholar 

  28. Shimizu K, Kondo R, Sakai K (2000) Inhibition of tyrosinase by flavonoids, stilbenes and related 4-substituted resorcinols: structure-activity investigations. Planta Med 66:11–15

    Article  CAS  PubMed  Google Scholar 

  29. Shin NH, Ryu SY, Choi EJ, Kang SH, Chang IM, Min KR, Kim Y (1998) Oxyresveratrol as the potent inhibitor on Dopa oxidase activity of mushroom tyrosinase. Biochem Biophys Res Commun 243:801–803

    Article  CAS  PubMed  Google Scholar 

  30. Tsuchihashi R, Kodera M, Sakamoto S, Nakajima Y, Yamazaki T, Niiho Y, Nohara T, Kinjo J (2009) Microbial transformation and bioactivation of isoflavones from Pueraria flowers by human intestinal bacterial strains. J Nat Med 63:254–260

    Article  CAS  PubMed  Google Scholar 

Download references


This study was supported by the Technology Development Program for Agriculture and Forestry, Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Young-Hee Lim.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 1344 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, JK., Kim, M., Cho, SG. et al. Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase inhibition. J Ind Microbiol Biotechnol 37, 631–637 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Biotransformation
  • Mulberroside A
  • Oxyresveratrol
  • Tyrosinase inhibitor