Salicylic acid in ginseng root alleviates skin hyperpigmentation disorders by inhibiting melanogenesis and melanosome transport

Eur J Pharmacol. 2021 Nov 5;910:174458. doi: 10.1016/j.ejphar.2021.174458. Epub 2021 Sep 1.


Abnormal melanogenesis and melanosome transport can cause skin pigmentation disorders that are often treated using ginseng-based formulation. We previously found that phenolic acid compounds in ginseng root could inhibit melanin production and as a skin-whitening agents. However, mechanisms of action underlying effects of ginseng phenolic acid monomers on melanogenesis remain unclear. This study was conducted to investigate effects of salicylic acid, a main ginseng root phenolic acid component, on melanogenesis and melanosome functions in melanocytes of zebrafish and other species. Salicylic acid exhibited no cytotoxicity and reduced melanin levels and tyrosinase activity in B16F10 murine melanoma cells and normal human epidermal melanocytes regardless of prior cell stimulation with α-melanocyte stimulating hormone. Additionally, salicylic acid treatment reduced expression of melanogenic enzymes tyrosinase, tyrosinase-related protein 1 and tyrosinase-related protein 2, while reducing expression of their master transcriptional regulator, microphthalmia-associated transcription factor. Moreover, reduced phosphorylation of cAMP response-element binding protein was observed due to reduced cAMP levels resulting from salicylic acid inhibition of upstream signal regulators (adenylyl cyclase and protein kinase A). Furthermore, salicylic acid treatment suppressed expression of transport complex-associated proteins melanophilin and myosin Va in two UVB-treated melanocytic cell lines, suppressed phagocytosis of fluorescent microspheres by UVB-stimulated human keratinocytes (HaCaT), inhibited protease-activated receptor 2 activation by reducing both Ca2+ release and activation of phosphoinositide 3 kinase/AKT and mitogen-activated protein kinases and induced anti-melanogenic effects in zebrafish. Collectively, these results indicate that salicylic acid within ginseng root can inhibit melanocyte melanogenesis and melanin transport, while also suppressing keratinocyte phagocytic function.

Keywords: Ginseng roots; Melanogenesis; Melanosome transport; Pigmentation; Salicylic acid.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Line
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Humans
  • Hyperpigmentation / drug therapy*
  • Intramolecular Oxidoreductases / metabolism
  • Keratinocytes / drug effects
  • Melanins / antagonists & inhibitors
  • Melanins / metabolism*
  • Melanocytes / drug effects
  • Melanosomes / drug effects
  • Melanosomes / metabolism*
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / metabolism
  • Panax / chemistry*
  • Phagocytosis / drug effects
  • Protein Transport / drug effects
  • Receptor, PAR-2 / metabolism
  • Salicylic Acid / pharmacology*
  • Signal Transduction / drug effects
  • Ultraviolet Rays
  • Zebrafish
  • alpha-MSH / pharmacology


  • F2RL1 protein, human
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Receptor, PAR-2
  • alpha-MSH
  • Cyclic AMP
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • Cyclic AMP-Dependent Protein Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
  • Salicylic Acid
  • Calcium