Archives of Pharmacal Research

, Volume 42, Issue 11, pp 977–989 | Cite as

Synthesis of arbutin–gold nanoparticle complexes and their enhanced performance for whitening

  • Jin Ju Park
  • Su Jung Hwang
  • Yu Sun Kang
  • Jisung Jung
  • Suryeon Park
  • Jee Eun Hong
  • Yohan ParkEmail author
  • Hyo-Jong LeeEmail author
Research Article


Arbutin, a natural polyphenol, possesses numerous biological activities including whitening, anti-oxidant, anti-cancer, anti-inflammatory activities, as well as strong reducing power, making it an ideal bioactive ingredient for preparing gold nanoparticles (GNPs). Previously, we developed a novel green, mild synthetic method for GNPs using glycosides such as arbutin as reducing agents and stabilizers. Herein, we optimized the synthetic method for glycoside–GNPs using arbutin, methyl β-d-glucoside, and phenyl β-d-glucoside and validated their whitening efficacy in vitro and in vivo. The resulting glycoside–GNPs were predominantly mono-dispersed and spherical (10.30–17.13 nm diameter). Compared with arbutin itself, arbutin–GNP complexes (GNP-A1 and GNP-P2) displayed enhanced whitening capabilities. Furthermore, GNP-P2 exhibited enhanced anti-inflammatory activity and lacked the toxicity associated with arbutin. Bioactive glycoside–GNP complexes may open new directions for cosmeceuticals, and GNP-P2 may serve as a useful whitening ingredient in future cosmeceutical applications.


Arbutin–gold nanoparticles Whitening Polyphenolic compounds Glycoside–GNPs Anti-inflammatory activity Cosmeceuticals 



This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2012270, NRF-2019R1C1C1003558) and the Ministry of Education, Science and Technology (2016R1D1A1B04930774).

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.


  1. Ahn EY, Hwang SJ, Choi MJ, Cho S, Lee HJ, Park Y (2018) Upcycling of jellyfish (Nemopilema nomurai) sea wastes as highly valuable reducing agents for green synthesis of gold nanoparticles and their antitumor and anti-inflammatory activity. Artif Cells Nanomed Biotechnol 46:1127–1136CrossRefGoogle Scholar
  2. Chen XJ, Zhang XQ, Liu Q, Zhang J, Zhou G (2018) Nanotechnology: a promising method for oral cancer detection and diagnosis. J Nanobiotechnol 16:52CrossRefGoogle Scholar
  3. Davis EC, Callender VD (2010) Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol 3:20–31PubMedPubMedCentralGoogle Scholar
  4. Draelos ZD (2007) Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 20:308–313CrossRefGoogle Scholar
  5. Elahi N, Kamali M, Baghersad MH (2018) Recent biomedical applications of gold nanoparticles: a review. Talanta 184:537–556CrossRefGoogle Scholar
  6. Ertam I, Mutlu B, Unal I, Alper S, Kivcak B, Ozer O (2008) Efficiency of ellagic acid and arbutin in melasma: a randomized, prospective, open-label study. J Dermatol 35:570–574CrossRefGoogle Scholar
  7. Hulkoti NI, Taranath TC (2014) Biosynthesis of nanoparticles using microbes—a review. Colloids Surf B 121:474–483CrossRefGoogle Scholar
  8. Hwang SJ, Lee HJ (2015) Phenyl-beta-D-glucopyranoside exhibits anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells. Inflammation 38:1071–1079CrossRefGoogle Scholar
  9. Hwang SJ, Kim YW, Park Y, Lee HJ, Kim KW (2014) Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm Res 63:81–90CrossRefGoogle Scholar
  10. Hwang SJ, Jun SH, Park Y, Cha SH, Yoon M, Cho S, Lee HJ, Park Y (2015) Green synthesis of gold nanoparticles using chlorogenic acid and their enhanced performance for inflammation. Nanomedicine 11:1677–1688CrossRefGoogle Scholar
  11. Inoue Y, Hasegawa S, Yamada T, Date Y, Mizutani H, Nakata S, Matsunaga K, Akamatsu H (2013) Analysis of the effects of hydroquinone and arbutin on the differentiation of melanocytes. Biol Pharm Bull 36:1722–1730CrossRefGoogle Scholar
  12. Jiang L, Wang D, Zhang Y, Li J, Wu Z, Wang Z, Wang D (2018) Investigation of the pro-apoptotic effects of arbutin and its acetylated derivative on murine melanoma cells. Int J Mol Med 41:1048–1054PubMedGoogle Scholar
  13. Jung J, Park S, Hong S, Ha MW, Park HG, Park Y, Lee HJ, Park Y (2014) Synthesis of gold nanoparticles with glycosides: synthetic trends based on the structures of glycones and aglycones. Carbohydr 386:57–61CrossRefGoogle Scholar
  14. Khan MS, Vishakante GD, Siddaramaiah H (2013) Gold nanoparticles: a paradigm shift in biomedical applications. Adv Colloid Interface Sci 199–200:44–58CrossRefGoogle Scholar
  15. Kwon SJ, Hwang SJ, Jung Y, Park HG, Kim MH, Park Y, Lee HJ (2017) A synthetic Nitraria alkaloid, isonitramine protects pancreatic beta-cell and attenuates postprandial hyperglycemia. Metabolism 70:107–115CrossRefGoogle Scholar
  16. Lee HJ, Kim KW (2012) Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells. Inflamm Res 61:817–825CrossRefGoogle Scholar
  17. Logan DW, Burn SF, Jackson IJ (2006) Regulation of pigmentation in zebrafish melanophores. Pigment Cell Res 19:206–213CrossRefGoogle Scholar
  18. Maeda K, Fukuda M (1996) Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 276:765–769PubMedGoogle Scholar
  19. Mittal AK, Chisti Y, Banerjee UC (2013) Synthesis of metallic nanoparticles using plant extracts. Biotechnol Adv 31:346–356CrossRefGoogle Scholar
  20. Nihei K, Kubo I (2003) Identification of oxidation product of arbutin in mushroom tyrosinase assay system. Bioorg Med Chem Lett 13:2409–2412CrossRefGoogle Scholar
  21. Ning L, Zhu B, Gao T (2017) Gold nanoparticles: promising agent to improve the diagnosis and therapy of cancer. Curr Drug 18:1055–1067CrossRefGoogle Scholar
  22. Polnikorn N (2010) Treatment of refractory melasma with the MedLite C6 Q-switched Nd:YAG laser and alpha arbutin: a prospective study. J Cosmet Laser Ther 12:126–131CrossRefGoogle Scholar
  23. Simon-Yarza T, Mielcarek A, Couvreur P, Serre C (2018) Nanoparticles of metal-organic frameworks: on the road to in vivo efficacy in biomedicine. Adv Mater 30:e1707365CrossRefGoogle Scholar
  24. Tada M, Kohno M, Niwano Y (2014) Alleviation effect of arbutin on oxidative stress generated through tyrosinase reaction with l-tyrosine and L-DOPA. BMC Biochem 15:23CrossRefGoogle Scholar
  25. Wu LH, Li P, Zhao QL, Piao JL, Jiao YF, Kadowaki M, Kondo T (2014) Arbutin, an intracellular hydroxyl radical scavenger, protects radiation-induced apoptosis in human lymphoma U937 cells. Apoptosis 19:1654–1663CrossRefGoogle Scholar
  26. Wu H, Zhao Y, Huang Q, Cai M, Pan Q, Fu M, An X, Xia Z, Liu M, Jin Y, He L, Shang J (2018) NK1R/5-HT1AR interaction is related to the regulation of melanogenesis. FASEB J 32:3193–3214CrossRefGoogle Scholar
  27. Yousefi F, Mahjoub S, Pouramir M, Khadir F (2013) Hypoglycemic activity of Pyrus biossieriana Buhse leaf extract and arbutin: inhibitory effects on alpha amylase and alpha glucosidase. Caspian J Intern Med 4:763–767PubMedPubMedCentralGoogle Scholar
  28. Yuan Q, Wang Y, Zhao L, Liu R, Gao F, Gao L, Gao X (2016) Peptide protected gold clusters: chemical synthesis and biomedical applications. Nanoscale 8:12095–12104CrossRefGoogle Scholar
  29. Zhang J, Chambers I, Yun S, Phillips J, Krause M, Hamza I (2018) Hrg1 promotes heme-iron recycling during hemolysis in the zebrafish kidney. PLoS Genet 14:e1007665CrossRefGoogle Scholar
  30. Zhou L, Fu X, Jiang L, Wang L, Bai S, Jiao Y, Xing S, Li W, Ma J (2017) Arbutin increases Caenorhabditis elegans longevity and stress resistance. PeerJ 5:e4170CrossRefGoogle Scholar
  31. Zhu W, Gao J (2008) The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders. J Investig Dermatol Symp Proc 13:20–24CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.College of Pharmacy and Inje Institute of Pharmaceutical Sciences and ResearchInje UniversityGimhaeSouth Korea

Personalised recommendations