AAPS PharmSciTech

, Volume 15, Issue 5, pp 1252–1262 | Cite as

The Melanogenesis-Inhibitory Effect and the Percutaneous Formulation of Ginsenoside Rb1

  • Lin Wang
  • Ai-Ping Lu
  • Zhi-Ling Yu
  • Ricky N. S. Wong
  • Zhao-Xiang Bian
  • Hoi-Hin Kwok
  • Patrick Ying-Kit Yue
  • Li-Min Zhou
  • HuBiao Chen
  • Min Xu
  • Zhijun YangEmail author
Research Article


Ginsenoside Rb1 (Rb1) is the most predominant ginsenoside isolated from the roots of ginseng (Panax ginseng C. A. Meyer). This compound is active in various human biological pathways that are involved in human collagen synthesis and inhibition of cell apoptosis. In this study, the skin-whitening effects of Rb1 were investigated in B16 melanoma cells. Our results showed that Rb1 inhibited melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 cells in a dose-dependent manner, which collectively indicated that Rb1 may have skin-whitening effects and may be formulated into skin-whitening products for skin care. Accordingly, a ginsenoside collagen transdermal patch was developed as a vehicle to topically deliver Rb1 into pig skin. The percutaneous permeation, retention within skin, and release in vitro of Rb1 from seven transdermal patch formulas were studied. It was determined that the best formula for ginsenoside collagen transdermal patch is made of protein collagen hydrolysate powder (PCHP) 2.0% (w/w), methyl cellulose (MC) 0.5% (w/w), polyethyleneglycol 6000 (PEG6000) 0.5% (w/w), ginsenoside 0.036% (w/w), azone 0.4% (v/w), menthol 0.20% (w/w), and water.


ginsenoside rb1 melanin permeation skin whitening transdermal patch 



This work was supported by Jiangsu Overseas Research and Training Program for University Prominent Young and Middle-aged Teachers and Presidents sponsored by Jiangsu Provincial Department of Education, and also by Hong Kong Baptist University FRG2/08-09/089. The authors also would like to greatly thank Mulin Yang for his proof reading and English correction and Dr. Yu Hua and Yuen Tsz-kin from the Center for Cancer and Inflammation Research of Hong Kong Baptist University for their patient technical guidance in B16 cell culture test.

Conflict of Interest

The authors declare no conflict of interest.


  1. 1.
    Martinez-Esparza M, Jimenez-Cervantes C, Solano F, Lozano JA, Garcia-Borron JC. Mechanisms of melanogenesis inhibition by tumor necrosis factor-alpha in B16/F10 mouse melanoma cells. Eur J Biochem. 1998;255(1):139–46.PubMedCrossRefGoogle Scholar
  2. 2.
    Leyden JJ, Shergill B, Micali G, Downie J, Wallo W. Natural options for the management of hyperpigmentation. J Eur Acad Dermatol Venereol. 2011;25(10):1140–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Callender VD, St Surin-Lord S, Davis EC, Maclin M. Postinflammatory hyperpigmentation: etiologic and therapeutic considerations. Am J Clin Dermatol. 2011;12(2):87–99.PubMedCrossRefGoogle Scholar
  4. 4.
    Cai BX, Jin SL, Luo D, Lin XF, Gao J. Ginsenoside Rb1 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. Biol Pharm Bull. 2009;32(5):837–41.PubMedCrossRefGoogle Scholar
  5. 5.
    Kang TH, Park HM, Kim YB, Kim H, Kim N, Do JH, et al. Effects of red ginseng extract on UVB irradiation-induced skin aging in hairless mice. J Ethnopharmacol. 2009;123(3):446–51.PubMedCrossRefGoogle Scholar
  6. 6.
    Lee J, Jung E, Lee J, Huh S, Kim J, Park M, et al. Panax ginseng induces human type I collagen synthesis through activation of Smad signaling. J Ethnopharmacol. 2007;109(1):29–34.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoi-Hin K, Ying-Kit YP, Nai-Ki M, Ngok-Shun WR. Ginsenoside Rb1 induces type I collagen expression through peroxisome proliferator-activated receptor-delta. Biochem Pharmacol. 2012;84:532–9.CrossRefGoogle Scholar
  8. 8.
    Longo C, Galimberti M, De Pace B, Pellacani G, Bencini PL. Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy. Laser Med Sci. 2013;28(3):769–76.CrossRefGoogle Scholar
  9. 9.
    Mizuta S, Nishizawa M, Sekiguchi F, Matsuo K, Yokoyama Y, Yoshinaka R. Enzymatic solubilization of collagen in the skin of diamond squid Thysanoteuthis rhombus: application of a fungal acid protease. Fish Sci. 2013;79(5):841–8.CrossRefGoogle Scholar
  10. 10.
    Han M, Sha X, Wu Y, Fang X. Oral absorption of ginsenoside Rb1 using in vitro and in vivo models. Planta Med. 2006;72(5):398–404.PubMedCrossRefGoogle Scholar
  11. 11.
    Moghimi HR, Williams AC, Barry BW. A lamellar matrix model for stratum corneum intercellular lipids. 5. Effects of terpene penetration enhancers on the structure and thermal behaviour of the matrix. Int J Pharm. 1997;146(1):41–54.CrossRefGoogle Scholar
  12. 12.
    Chang TS, Chen CT. Inhibitory effect of homochlorcyclizine on melanogenesis in alpha-melanocyte stimulating hormone-stimulated mouse B16 melanoma cells. Arch Pharm Res. 2012;35(1):119–27.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee JH, Jang JY, Park C, Kim BW, Choi YH, Choi BT. Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells. Int J Mol Med. 2010;26(1):101–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Ye Y, Chou GX, Wang H, Chu JH, Yu ZL. Flavonoids, apigenin and icariin exert potent melanogenic activities in murine B16 melanoma cells. Phytomedicine. 2010;18(1):32–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Yun CY, Kim D, Lee WH, Park YM, Lee SH, Na M, et al. Torilin from torilis japonica inhibits melanin production in alpha-melanocyte stimulating hormone-activated B16 melanoma cells. Planta Med. 2009;75(14):1505–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Hunt G, Todd C, Cresswell JE, Thody AJ. Alpha-melanocyte-stimulating hormone and its analog Nle(4)Dphe(7)alpha-Msh affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes. J Cell Sci. 1994;107:205–11.PubMedGoogle Scholar
  17. 17.
    Liu X, Chen T, Liu XS, Chen Y, Wang LH. Penetration effect of ostrich oil as a promising vehicle on transdermal delivery of sinomenine. J Oleo Sci. 2013;62(9):657–64.PubMedCrossRefGoogle Scholar
  18. 18.
    TangJun W-b W. A rapid method for the simultaneous determination of five saponins in Xueshuaotong injection with ultra performance liquid chromatography. Chin J Pharm Anal. 2008;28(1):97–9.Google Scholar
  19. 19.
    Yao-xuan X, Ya-zhu L. UPLC determination of ginsenoside Rg1, ginsenoside Rb1and notoginsenoside R1 in Panax Notoginseng. J Guangdong Pharmaceutical Univ. 2011;27(5):489–92.Google Scholar
  20. 20.
    Yang Z, Gao S, Wang JR, Yin TJ, Teng Y, Wu BJ, et al. Enhancement of oral bioavailability of 20(S)-ginsenoside Rh2 through improved understanding of its absorption and efflux mechanisms. Drug Metab Dispos. 2011;39(10):1866–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang JH, Liu M, Jin HJ, Deng LD, Xing JF, Dong AJ. In vitro enhancement of lactate esters on the percutaneous penetration of drugs with different lipophilicity. AAPS PharmSciTech. 2010;11(2):894–903.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Wang T, Gu XC. In vitro percutaneous permeation of the repellent DEET and the sunscreen oxybenzone across human skin. J Pharm Pharm Sci. 2007;10(1):17–25.PubMedGoogle Scholar
  23. 23.
    Yao-Dong Y. Design and development of sustained-released preparation and controlled-released preparation (Huan shi kong shi zhi ji de she ji yu kai fa). Beijing: China Medical Science and Technology Press; 2006.Google Scholar
  24. 24.
    Monti D, Tampucci S, Chetoni P, Burgalassi S, Saino V, Centini M, et al. Permeation and distribution of ferulic acid and its alpha-cyclodextrin complex from different formulations in hairless rat skin. Aaps Pharmscitech. 2011;12(2):514–20.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Stahl J, Braun M, Siebert J, Kietzmann M. The percutaneous permeation of a combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol (octenisept (R)) through skin of different species in vitro. BMC Vet Res. 2011;7.Google Scholar
  26. 26.
    Fares H, Zatz J. Measurement of drug release from topical gels using two types of apparatus. J Pharm Technol. 1995;1:52–6.Google Scholar
  27. 27.
    Bunge AL. Release rates from topical formulations containing drugs in suspension. J Control Release. 1998;52(1–2):141–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Schweikardt T, Olivares C, Solano F, Jaenicke E, Garcia-Borron JC, Decker H. A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations. Pigment Cell Res. 2007;20(5):394–401.PubMedCrossRefGoogle Scholar
  29. 29.
    Bos JD, Meinardi MMHM. The 500 dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Riviere JE, Brooks JD. Predicting skin permeability from complex chemical mixtures: dependency of quantitative structure permeation relationships on biology of skin model used. Toxicol Sci. 2011;119(1):224–32.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Forster M, Bolzinger MA, Fessi H, Briancon S. Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery. Eur J Dermatol. 2009;19(4):309–23.PubMedGoogle Scholar
  32. 32.
    Sanghvi P, Collins C. Comparison of diffusion studies of hydrocortisone between the Franz cell and the enhancer cell. Drug Dev Ind Pharm. 1993;19(13):1573–85.CrossRefGoogle Scholar
  33. 33.
    Corbo M, Schultz T, Wong G, Buskirk GV. Development and validation of in vitro release testing methods for semisolid formulations. Pharm Technol. 1993;17(9):112–28.Google Scholar
  34. 34.
    Korsmeyer R, Gurny R, Doelker E, Buri P, Peppas N. Mechanism of solute release from porous hydro-matrices and other factors may be responsible. Int J Pharm. 1983;15:25–35.CrossRefGoogle Scholar
  35. 35.
    Crank J. The mathematics of diffusion. London: Oxford University Press; 1979.Google Scholar
  36. 36.
    Ling Z, Zi-ping Y, Li Z, Li C, Yu-jing F. Effects of different penetration enhancers on transdermal behavior of L-carnitine in vitro. Chin J New Drugs. 2012;21(5):559–62.Google Scholar
  37. 37.
    Cornwell PA, Barry BW, Bouwstra JA, Gooris GS. Modes of action of terpene penetration enhancers in human skin differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies. Int J Pharm. 1996;127(1):9–26.CrossRefGoogle Scholar
  38. 38.
    Ongpipattanakul B, Burnette R, Potts R, Francoeur M. Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm Res. 1991;8:350–4.PubMedCrossRefGoogle Scholar
  39. 39.
    Bouwstra J, Peschier L, Brussee J, Bodde H. Effect of nalkyl-azocycloheptan-2-ones including azone on the thermal behaviour of human stratum corneum. Int J Pharm. 1989;52:47–54.CrossRefGoogle Scholar
  40. 40.
    Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004;56(5):603–18.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Lin Wang
    • 1
    • 2
  • Ai-Ping Lu
    • 1
  • Zhi-Ling Yu
    • 1
  • Ricky N. S. Wong
    • 3
  • Zhao-Xiang Bian
    • 1
  • Hoi-Hin Kwok
    • 3
  • Patrick Ying-Kit Yue
    • 3
  • Li-Min Zhou
    • 1
  • HuBiao Chen
    • 1
  • Min Xu
    • 1
  • Zhijun Yang
    • 1
    Email author
  1. 1.School of Chinese MedicineHong Kong Baptist UniversityHong KongChina
  2. 2.College of PharmacySuzhou Health CollegeSuzhouChina
  3. 3.Department of Biology, Faculty of ScienceHong Kong Baptist UniversityHong KongChina

Personalised recommendations