Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

Linarin enhances melanogenesis in B16F10 cells via MAPK and PI3K/AKT signaling pathways

  • Oh, So-Yeon (Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University) ;
  • Kang, Jin Kyu (Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University) ;
  • Hyun, Chang-Gu (Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University)
  • Received : 2021.10.24
  • Accepted : 2021.11.16
  • Published : 2021.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, we discovered for the first time that linarin, a flavonoid compound, enhances melanin biosynthesis in B16F10 cells, and subsequently elucidated the underlying mechanism of linarin-induced melanogenesis. Linarin showed no cytotoxicity at a concentration of 42 μM and significantly increased intracellular tyrosinase activity and melanin content in B16F10 cells. Mechanistic analysis showed that linarin increased the expression of tyrosinase, tyrosinase-related protein 1 (TRP-1), and microphthalmia-associated transcription factor (MITF) that are related to melanogenesis. Moreover, linarin decreased the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT). Finally, we evaluated the effect of the structure-activity relationship of linarin and its aglycone on melanogenesis. The results indicated that linarin enhances the expression of melanogenic proteins by activating MITF expression via the modulation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B signaling pathways in B16F10 cells, thereby enhancing melanogenesis.

Keywords

Acknowledgement

This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Industry Innovation Foundation Project (P0018139).

References

  1. Qu Y, Zhan Q, Du S, Ding Y, Fang B, Du W, Wu Q, Yu H, Li L, Huang W (2020) Catalysis-based specific detection and inhibition of tyrosinase and their application. J Pharm Anal 10: 414-425. doi: 10.1016/j.jpha.2020.07.004.
  2. Agarwal K, Podder I, Kassir M, Vojvodic A, Schwartz RA, Wollina U, Valle Y, Lotti T, Rokni GR, Grabbe S, Goldust M (2020) Therapeutic options in vitiligo with special emphasis on immunomodulators: A comprehensive update with review of literature. Dermatol Ther 33: e13215. doi: 10.1111/dth.13215
  3. Lv J, An X, Jiang S, Yang Y, Song G, Gao R (2020) Protoporphyrin IX Stimulates Melanogenesis, melanocyte dendricity, and melanosome transport through the cGMP/PKG pathway. Front Pharmacol 11: 569368. doi: 10.3389/fphar.2020.569368
  4. Qi W, Chen Y, Sun S, Xu X, Zhan J, Yan Z, Shang P, Pan X, Liu H (2021) Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis. Aging (Albany NY) 13: 5369-5382. doi: 10.18632/aging.202469
  5. Pan H, Zhang J, Wang Y, Cui K, Cao Y, Wang L, Wu Y (2019) Linarin improves the dyskinesia recovery in Alzheimer's disease zebrafish by inhibiting the acetylcholinesterase activity. Life Sci 222: 112-116. doi: 10.1016/j.lfs.2019.02.046
  6. Nugroho A, Lim SC, Choi J, Park HJ (2013) Identification and quantification of the sedative and anticonvulsant flavone glycoside from Chrysanthemum boreale. Arch Pharm Res 36: 51-60. doi: 10.1007/s12272-013-0015-8
  7. Fernandez S, Wasowski C, Paladini AC, Marder M (2004) Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharmacol Biochem Behav 77: 399-404. doi: 10.1016/j.pbb.2003.12.003
  8. Fu T, Chai B, Shi Y, Dang Y, Ye X (2019) Fargesin inhibits melanin synthesis in murine malignant and immortalized melanocytes by regulating PKA/CREB and P38/MAPK signaling pathways. J Dermatol Sci 94: 213-219. doi: 10.1016/j.jdermsci.2019.03.004
  9. Hwang YS, Oh SW, Park SH, Lee J, Yoo JA, Kwon K, Park SJ, Kim J, Yu E, Cho JY, Lee J (2019) Melanogenic effects of maclurin are mediated through the activation of cAMP/PKA/CREB and p38 MAPK/CREB signaling pathways. Oxid Med Cell Longev 2019: 9827519. doi: 10.1155/2019/9827519
  10. Ko JH, Lee N, Kang HK, Kim BS, Lee JN, Hyun CG (2020) Anti-melanogenic effects of hot-water extracts from Torreya nucifera via MAPKs and cAMP signaling pathway on B16F10 cells. Pharmazie 75: 565-570. doi: 10.1691/ph.2020.0522
  11. Sangkaew O, Yompakdee C (2020). Fermented unpolished black rice (Oryza sativa L.) inhibits melanogenesis via ERK, p38, and AKT phosphorylation in B16F10 melanoma cells. J Microbiol Biotechnol 30: 1184-1194. doi : 10.4014/jmb.2003.03019