Skip to main content
SpringerLink
Log in

Oleanolic acid from Fragaria ananassa calyx leads to inhibition of α-MSH-induced melanogenesis in B16-F10 melanoma cells

  • Article
  • Published:
Journal of the Korean Society for Applied Biological Chemistry Submit manuscript

Abstract

Natural products with non-toxic and environmentally friendly properties are good sources for skin-whitening and brightening cosmetic agents. Strawberries (Fragaria ananassa), and their parts are used as cosmetic agents, because they contain high levels of bioactive substances. We isolated and identified compounds from F. ananassa calyx. Oleanolic acid has multiple biological activities, including anti-tumor, anti-angiogenic, antiinflammatory, anti-oxidant, and pro-apoptotic effects. However, no study has investigated the influence of oleanolic acid on melanin synthesis in B16-F10 melanoma cells. In the present study, we investigated the effect of oleanolic acid on melanin biosynthesis in B16-F10 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH). Oleanolic acid-mediated melanogenesis inhibition was studied by measuring intracellular and secreted melanin levels and by using Western blot and semiquantitative reverse transcriptase-polymerase chain reaction analyses. Oleanolic acid suppressed melanin release and expression, resulting in a significant dose-dependent decrease in secreted and intracellular melanin levels and cellular tyrosinase activity. Furthermore, it inhibited the expression of melanogenesis-associated factors, including tyrosinase, tyrosinase-related proteins-1 and -2, and microphthalmia-associated transcription factor, in α-MSH-stimulated B16-F10 melanoma cells. The results of the present study can contribute to the development of cosmetic agents utilizing the skin whitening and brightening effect of oleanolic acid, which will likely have a wide range of applications in the cosmetic industry and/or clinical practice in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andersson D, Liu JJ, Nilsson A, and Duan RD (2003) Ursolic acid inhibits proliferation and stimulates apoptosis in HT29 cells following activation of alkaline sphingomyelinase. Anticancer Res 23, 3317–22.

    CAS  Google Scholar 

  • Ando H, Kondoh H, Ichihashi M, and Hearing VJ (2007) Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J Invest Dermatol 127, 751–61.

    Article  CAS  Google Scholar 

  • Baek JH and Lee SH (2010) Isolation and molecular cloning of venom peptides from orancistrocerus drewseni (hymenoptera: Eumenidae). Toxicon 55, 711–8.

    Article  CAS  Google Scholar 

  • Bellei B, Flori E, Izzo E, Maresca V, and Picardo M (2008) GSK3-β inhibition promotes melanogenesis in mouse B16 melanoma cells and normal human melanocytes. Cell Signal 20, 1750–61.

    Article  CAS  Google Scholar 

  • Cijo George V, Naveen Kumar D, Suresh P, and Kumar RA (2014) Oleanolic acid inhibits cell growth and induces apoptosis in A375 melanoma cells. Biomedicine & Preventive Nutrition 4, 95–9.

    Article  Google Scholar 

  • Cui T, Li J, Kayahara H, Ma L, Wu L, and Nakamura K (2006) Quantification of the polyphenols and triterpene acids in chinese hawthorn fruit by high-performance liquid chromatography. J Agric Food Chem 54, 4574–81.

    Article  CAS  Google Scholar 

  • Del Marmol V and Beermann F (1996) Tyrosinase and related proteins in mammalian pigmentation. FEBS Lett 381, 165–8.

    Article  Google Scholar 

  • Giampieri F, Tulipani S, Alvarez-Suarez JM, Quiles JL, Mezzetti B, and Battino M (2012) The strawberry: Composition, nutritional quality, and impact on human health. Nutrition 28, 9–19.

    Article  CAS  Google Scholar 

  • Gillbro J and Olsson M (2011) The melanogenesis and mechanisms of skinlightening agents-existing and new approaches. Int J Cosmetic Sci 33, 210–21.

    Article  CAS  Google Scholar 

  • Hearing VJ and Jiménez M (1987) Mammalian tyrosinase- the critical regulatory control point in melanocyte pigmentation. Int J Biochem 19, 1141–7.

    Article  CAS  Google Scholar 

  • Hearing VJ, Korner AM, and Pawelek JM (1982) New regulators of melanogenesis are associated with purified tyrosinase isozymes. J Invest Dermatol 79, 16–8.

    Article  CAS  Google Scholar 

  • Jang S, Yee S, Choi J, Choi M, Do G, Jeon S, Yeo J, Kim M, Seo K, and Lee M (2009) Ursolic acid enhances the cellular immune system and pancreatic -β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol 9, 113–9.

    Article  CAS  Google Scholar 

  • Karlund A, Salminen JP, Koskinen P, Ahern JR, Karonen M, Tiilikkala K, and Karjalainen RO (2014) Polyphenols in strawberry (fragaria × ananassa) leaves induced by plant activators. J Agric Food Chem 62, 4592–600.

    Article  CAS  Google Scholar 

  • Kim D, Baek JH, Kang C, Yoo M, Sung J, Kim D, Chung H, Kim ND, Choi YH, and Lee S (2000) Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication. Int J Cancer 87, 629–36.

    Article  CAS  Google Scholar 

  • Kuzumaki T, Matsuda A, Wakamatsu K, Ito S, and Ishikawa K (1993) Eumelanin biosynthesis is regulated by coordinate expression of tyrosinase and tyrosinase-related protein-1 genes. Exp Cell Res 207, 33–40.

    Article  CAS  Google Scholar 

  • Langan E, Nie Z, and Rhodes L (2010) Melanotropic peptides: More than just ‘Barbie drugs’ and ‘suntan jabs’? Br J Dermatol 163, 451–5.

    Article  CAS  Google Scholar 

  • Levy C, Khaled M, and Fisher DE (2006) MITF: Master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12, 406–14.

    Article  CAS  Google Scholar 

  • Liu J (1995) Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 49, 57–68.

    Article  CAS  Google Scholar 

  • Liu J (2005) Oleanolic acid and ursolic acid: Research perspectives. J Ethnopharmacol 100, 92–4.

    Article  CAS  Google Scholar 

  • Mishima Y (1994) Molecular and biological control of melanogenesis through tyrosinase genes and intrinsic and extrinsic regulatory factors. Pigment Cell Res 7, 376–87.

    Article  CAS  Google Scholar 

  • Mitani K, Takano F, Kawabata T, Allam AE, Ota M, Takahashi T, Yahagi N, Sakurada C, Fushiya S, and Ohta T (2013) Suppression of melanin synthesis by the phenolic constituents of sappanwood (caesalpinia sappan). Planta Med 79, 37–44.

    CAS  Google Scholar 

  • Mountjoy KG, Robbins LS, Mortrud MT, and Cone RD (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248–51.

    Article  CAS  Google Scholar 

  • Munoz C, Hoffmann T, Escobar NM, Ludemann F, Botella MA, Valpuesta V, and Schwab W (2010) The strawberry fruit fra a allergen functions in flavonoid biosynthesis. Mol Plant 3, 113–24.

    Article  CAS  Google Scholar 

  • Niikawa M, Hayashi H, Sato T, Nagase H, and Kito H (1993) Isolation of substances from glossy privet (Ligustrum lucidum Ait.) inhibiting the mutagenicity of benzo[a]pyrene in bacteria. Mutation Research/Genetic Toxicology 319, 1–9.

    Article  CAS  Google Scholar 

  • Ovesna Z, Vachalkova A, Horvathova K, and Tothova D (2004) Pentacyclic triterpenoic acids: New chemoprotective compounds. minireview Neoplasma 51, 327–33.

    CAS  Google Scholar 

  • Parvez S, Kang M, Chung H, Cho C, Hong M, Shin M, and Bae H (2006) Survey and mechanism of skin depigmenting and lightening agents. Phytother Res 20, 921–34.

    Article  CAS  Google Scholar 

  • Perez-Bernal A, Muñoz-Pérez MA, and Camacho F (2000) Management of facial hyperpigmentation. Am J Clin Dermatol 1, 261–8.

    Article  CAS  Google Scholar 

  • Plonka PM and Grabacka M (2006) Melanin synthesis in microorganisms-biotechnological and medical aspects. Acta Biochim Pol 53, 429–43.

    CAS  Google Scholar 

  • Prota G (1988) Progress in the chemistry of melanins and related metabolites. Med Res Rev 8, 525–56.

    Article  CAS  Google Scholar 

  • Scott MC, Wakamatsu K, Ito S, Kadekaro AL, Kobayashi N, Groden J, Kavanagh R, Takakuwa T, Virador V, Hearing VJ, and Abdel-Malek ZA (2002) Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation. J Cell Sci 115, 2349–55.

    CAS  Google Scholar 

  • Shigeta Y, Imanaka H, Ando H, Ryu A, Oku N, Baba N, and Makino T (2004) Skin whitening effect of linoleic acid is enhanced by liposomal formulations. Biol Pharm Bull 27, 591–4.

    Article  CAS  Google Scholar 

  • Takada K, Nakane T, Masuda K, and Ishii H (2010) Ursolic acid and oleanolic acid, members of pentacyclic triterpenoid acids, suppress TNF- a-induced E-selectin expression by cultured umbilical vein endothelial cells. Phytomedicine 17, 1114–9.

    Article  CAS  Google Scholar 

  • Tuerxuntayi A, Liu Y, Tulake A, Kabas M, Aiden E, and Aisa HA (2014) Kaliziri extract upregulates tyrosinase, TRP-1, TRP-2 and MITF expression in murine B16 melanoma cells. BMC Complementary and Alternative Medicine 14, 166.

    Article  Google Scholar 

  • Virador V, Matsunaga N, Matsunaga J, Valencia J, Oldham RJ, Kameyama K, Peck GL, Ferrans VJ, Vieira WD, and AbdelMalek ZA (2001) Production of MelanocyteSpecific antibodies to human melanosomal proteins: Expression patterns in normal human skin and in cutaneous pigmented lesions. Pigment Cell Res 14, 289–97.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Skin Research Institute, Korea Kolmar Corporation, 12-11, Dukgogae-gil, Sejong, Republic of Korea

    Sang Keun Han

  2. GFC. Co., Ltd, #309, Tower-Dong, Heungdeok IT valley, 13, Heungdeok 1-Ro, Giheung-Gu, Yongin-City, Gyeonggi-Do, 446-908, Republic of Korea

    Yun Gi Kim, Hee Cheol Kang, Jeong Ran Huh, Ji Yeoung Kim & Dong-Geol Lee

  3. Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin-City, Gyeonggi-Do, 446-701, Republic of Korea

    Nam-In Baek

  4. Department of Industrial Engineering Chemistry, College of Engineering, Chungbuk National University, Cheongju, Chungcheongbuk-do, 362-763, Republic of Korea

    Dong-Kyu Lee

Authors
  1. Sang Keun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun Gi Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hee Cheol Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeong Ran Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ji Yeoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nam-In Baek
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dong-Kyu Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dong-Geol Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong-Kyu Lee or Dong-Geol Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Han, S.K., Kim, Y.G., Kang, H.C. et al. Oleanolic acid from Fragaria ananassa calyx leads to inhibition of α-MSH-induced melanogenesis in B16-F10 melanoma cells. J Korean Soc Appl Biol Chem 57, 735–742 (2014). https://doi.org/10.1007/s13765-014-4225-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13765-014-4225-7

Keywords

Search

Navigation