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

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.

[1]  Shoshi Mizuta,et al.  Enzymatic solubilization of collagen in the skin of diamond squid Thysanoteuthis rhombus: application of a fungal acid protease , 2013, Fisheries Science.

[2]  C. Longo,et al.  Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy , 2013, Lasers in Medical Science.

[3]  Majella E Lane,et al.  Skin penetration enhancers. , 2013, International journal of pharmaceutics.

[4]  R. Wong,et al.  Ginsenoside Rb₁ induces type I collagen expression through peroxisome proliferator-activated receptor-delta. , 2012, Biochemical pharmacology.

[5]  Te-Sheng Chang,et al.  Inhibitory effect of homochlorcyclizine on melanogenesis in α-melanocyte stimulating hormone-stimulated mouse B16 melanoma cells , 2012, Archives of pharmacal research.

[6]  Taijun Yin,et al.  Enhancement of Oral Bioavailability of 20(S)-Ginsenoside Rh2 through Improved Understanding of Its Absorption and Efflux Mechanisms , 2011, Drug Metabolism and Disposition.

[7]  J. Leyden,et al.  Natural options for the management of hyperpigmentation , 2011, Journal of the European Academy of Dermatology and Venereology : JEADV.

[8]  M. Braun,et al.  The percutaneous permeation of a combination of 0.1% octenidine dihydrochloride and 2% 2-phenoxyethanol (octenisept®) through skin of different species in vitro , 2011, BMC veterinary research.

[9]  D. Monti,et al.  Permeation and Distribution of Ferulic Acid and Its α-Cyclodextrin Complex from Different Formulations in Hairless Rat Skin , 2011, AAPS PharmSciTech.

[10]  Zhi-Ling Yu,et al.  Flavonoids, apigenin and icariin exert potent melanogenic activities in murine B16 melanoma cells. , 2010, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[11]  Yung-Hyun Choi,et al.  Curcumin suppresses α-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells , 2010 .

[12]  H. Min,et al.  The expressions of carbonic anhydrase 9 and vascular endothelial growth factor in astrocytic tumors predict a poor prognosis. , 2010, International journal of molecular medicine.

[13]  Jinfeng Xing,et al.  In vitro Enhancement of Lactate Esters on the Percutaneous Penetration of Drugs with Different Lipophilicity , 2010, AAPS PharmSciTech.

[14]  Hatem Fessi,et al.  Topical delivery of cosmetics and drugs. Molecular aspects of percutaneous absorption and delivery. , 2009, European journal of dermatology : EJD.

[15]  H. Park,et al.  Effects of red ginseng extract on UVB irradiation-induced skin aging in hairless mice. , 2009, Journal of ethnopharmacology.

[16]  Mi Kyeong Lee,et al.  Torilin from Torilis japonica inhibits melanin production in alpha-melanocyte stimulating hormone-activated B16 melanoma cells. , 2009, Planta medica.

[17]  D. Luo,et al.  Ginsenoside Rb1 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. , 2009, Biological & pharmaceutical bulletin.

[18]  E. Jaenicke,et al.  A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations. , 2007, Pigment cell research.

[19]  Jongsung Lee,et al.  Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling. , 2007, Journal of ethnopharmacology.

[20]  Xiao-ling Fang,et al.  Oral Absorption of Ginsenoside Rb1 using in vitro and in vivo Models , 2006, Planta medica.

[21]  J. Bos,et al.  The 500 Dalton rule for the skin penetration of chemical compounds and drugs , 2000, Experimental dermatology.

[22]  F. Solano,et al.  Mechanisms of melanogenesis inhibition by tumor necrosis factor-alpha in B16/F10 mouse melanoma cells. , 1998, European journal of biochemistry.

[23]  A. Bunge.  Release rates from topical formulations containing drugs in suspension. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[24]  Brian W. Barry,et al.  A lamellar matrix model for stratum corneum intercellular lipids. II. Effect of geometry of the stratum corneum on permeation of model drugs 5-fluorouracil and oestradiol , 1996 .

[25]  J. Bouwstra,et al.  Modes of action of terpene penetration enhancers in human skin; Differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies , 1996 .

[26]  Russell O. Potts,et al.  Evidence that Oleic Acid Exists in a Separate Phase Within Stratum Corneum Lipids , 1991, Pharmaceutical Research.

[27]  J. Brussee,et al.  Effect of N-alkyl-azocycloheptan-2-ones including azone on the thermal behaviour of human stratum corneum , 1989 .

[28]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[29]  Xue-song Liu,et al.  Penetration effect of ostrich oil as a promising vehicle on transdermal delivery of sinomenine. , 2013, Journal of oleo science.

[30]  Feng Yu-jing.  Effects of different penetration enhancers on transdermal behavior of L-carnitine in vitro , 2012 .

[31]  J. Riviere,et al.  Predicting skin permeability from complex chemical mixtures: dependency of quantitative structure permeation relationships on biology of skin model used. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  Lin Ya-zhu.  UPLC determination of ginsenoside Rg_1,ginsenoside Rb_1 and notoginsenoside R_1 in Panax Notoginseng , 2011 .

[33]  Yung-Hyun Choi,et al.  Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells. , 2010, International journal of molecular medicine.

[34]  Wu Wei-bao.  A rapid method for the simultaneous determination of five saponins in Xueshuantong injection with ultra performance liquid chromatography , 2008 .

[35]  X. Gu,et al.  In vitro percutaneous permeation of the repellent DEET and the sunscreen oxybenzone across human skin. , 2007, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[36]  J. Wang,et al.  Chin. J. Pharm. Anal. , 2007 .

[37]  Adrian C. Williams,et al.  Penetration enhancers. , 2004, Advanced drug delivery reviews.

[38]  H. Moghimi,et al.  A lamellar matrix model for stratum corneum intercellular lipids. V. Effects of terpene penetration enhancers on the structure and thermal behaviour of the matrix , 1997 .

[39]  A. Thody,et al.  Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes. , 1994, Journal of cell science.

[40]  G. K. Wong,et al.  DEVELOPMENT AND VALIDATION OF IN VITRO RELEASE TESTING METHODS FOR SEMISOLID FORMULATIONS , 1993 .

[41]  C. C. Collins,et al.  Comparison of Diffusion Studies of Hydrocortisone Between the Franz Cell and the Enhancer Cell , 1993 .

[42]  John Crank,et al.  The Mathematics Of Diffusion , 1956 .