Ann Dermatol.  2015 Jun;27(3):250-256. 10.5021/ad.2015.27.3.250.

Tranexamic Acid Diminishes Laser-Induced Melanogenesis

• Kim MS
• Bang SH
• Kim JH
• Shin HJ
• Choi JH
• Chang SE

• KMID: 2352494
• DOI: http://doi.org/10.5021/ad.2015.27.3.250

Abstract

BACKGROUND
The treatment of post-inflammatory hyperpigmentation (PIH) remains challenging. Tranexamic acid, a well-known anti-fibrinolytic drug, has recently demonstrated a curative effect towards melasma and ultraviolet-induced PIH in Asian countries. However, the precise mechanism of its inhibitory effect on melanogenesis is not fully understood.
OBJECTIVE
In order to clarify the inhibitory effect of tranexamic acid on PIH, we investigated its effects on mouse melanocytes (i.e., melan-a cells) and human melanocytes.
METHODS
Melan-a cells and human melanocytes were cultured with fractional CO2 laser-treated keratinocyte-conditioned media. Melanin content and tyrosinase activity were evaluated in cells treated with or without tranexamic acid. Protein levels of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were evaluated in melan-a cells. Signaling pathway molecules involved in melanogenesis in melanoma cells were also investigated.
RESULTS
Tranexamic acid-treated melanocytes exhibited reduced melanin content and tyrosinase activity. Tranexamic acid also decreased tyrosinase, TRP-1, and TRP-2 protein levels. This inhibitory effect on melanogenesis was considered to be involved in extracellular signal-regulated kinase signaling pathways and subsequently microphthalmia-associated transcription factor degradation.
CONCLUSION
Tranexamic acid may be an attractive candidate for the treatment of PIH.

Keyword

Hyperpigmentation; Melanocytes; Tranexamic acid

MeSH Terms

Animals
Asian Continental Ancestry Group
Humans
Hyperpigmentation
MART-1 Antigen
Melanins
Melanocytes
Melanoma
Melanosis
Mice
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase
Phosphotransferases
Tranexamic Acid*
MART-1 Antigen
Melanins
Microphthalmia-Associated Transcription Factor
Monophenol Monooxygenase
Phosphotransferases
Tranexamic Acid

Figure

• 

  Fig. 1 Laser-treated keratinocyte-conditioned medium induced significant increases of inflammatory mediators. Inflammatory mediators including interleukin (IL)-1, IL-8, and prostaglandin E2 (PGE2) were significantly higher in laser-treated keratinocyteconditioned medium (blue) than non-treated keratinocyteconditioned medium (red). Data are mean±standard deviation. **p<0.01; Student's t-test.

• 

  Fig. 2 Laser-treated keratinocyte-conditioned medium (LT-KCM) induced increased melanin content and tyrosinase activity. Melan-a cells and human melanocytes were cultured in the presence of LT-KCM. The melanin contents (% of control) in both melan-a cells (A) and human melanocytes (B) are shown. Tyrosinase activity (% of control) in cultured melan-a cells (C) is shown. Data are mean±standard deviation. *p<0.05, **p<0.01; Student's t-test.

• 

  Fig. 3 Tranexamic acid (TA) decreased melanin content in melan-a cells. Melan-a cells were cultured in the presence of laser-treated keratinocyte-conditioned medium (LT-KCM). Arbutin and tranexamic acid inhibited melanin content in cultured melan-a cells. Data are mean±standard deviation. *p<0.05, **p<0.01; Student's t-test.

• 

  Fig. 4 Tranexamic acid (TA) decreased melanin content in human melanocytes. Human melanocytes were cultured in the presence of laser-treated keratinocyte-conditioned medium (LT-KCM). Data are mean±standard deviation.

• 

  Fig. 5 Tranexamic acid (TA) reduced tyrosinase activity in melan-a cells. Melan-a cells were cultured in the presence of laser-treated keratinocyte-conditioned medium (LT-KCM). Arbutin and tranexamic acid reduced tyrosinase activity (% of control) in cultured melan-a cells. Data are mean±standard deviation. *p<0.05, **p<0.01; Student's t-test.

• 

  Fig. 6 Tranexamic acid (TA) decreased protein levels of melanogenesis-related enzymes. Protein levels of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were higher in melan-a cells cultured with laser-treated keratinocyte-conditioned medium (LT-KCM) than keratinocyte conditioned medium (KCM) (CTL1 vs. CTL2) in western blot analysis. However, after TA treatment, their protein levels decreased in a dose-dependent manner. Arbutin (A100) was used as a positive control, and equal protein loading was confirmed by using β-actin. CTL1: control 1 (KCM without laser treatment), CTL2: control 2 (LT-KCM), A100: arbutin 100 mg/L, T10: 10 mg/L TA, T50: 50 mg/L TA, T100: 100 mg/L TA.

• 

  Fig. 7 Tranexamic acid (TA) stimulated the extracellular signal-regulated kinase (ERK) signaling pathway and decreased protein levels of microphthalmia-associated transcription factor (MITF). Protein levels of ERK, phosphorylated ERK (p-ERK), and MITF after TA treatment were evaluated by western blot analysis using B16F10 cells. Sustained activation of ERK was observed; in particular, p-ERK was elevated until 24 hours after TA treatment. MITF protein level decreased in a time-dependent manner.

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