Abstract
Background: Liquiritin (LQ) and its aglycone, liquiritigenin (LQG), are major flavonoids in licorice root (Glycyrrhiza spp.). Our preliminary screening identified LQ and LQG, which promote melanin synthesis in the melanoma cells. In this study, we investigated the molecular mechanism of melanin synthesis activated by LQ and LQG. Methods: Murine (B16-F1) and human (HMVII) melanoma cell lines were treated with LQ or LQG. After incubation, melanin contents, intracellular tyrosinase activity, and cell viability were evaluated. Protein levels were determined using Western blotting. Results: LQ and LQG activated melanin synthesis and intracellular tyrosinase activity. The induction of melanin and intracellular tyrosinase activity by LQG was higher than that by LQ. LQ and LQG induced the expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. LQ and LQG also enhanced microphthalmia-associated transcription factor (MITF) expression, and cyclic AMP-responsive element-binding protein (CREB) phosphorylation. The phosphorylation of p38 and extracellular signal-regulated kinase (ERK), but not Akt, was significantly increased by LQ or LQG. Furthermore, LQ- or LQG-mediated melanin synthesis was partially blocked by p38 inhibitor (SB203580) and protein kinase A (PKA) inhibitor (H-89); however, ERK kinase (MEK) inhibitor (U0126) and phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002) had no effect. Conclusions: The results suggest that LQ and LQG enhance melanin synthesis by upregulating the expression of melanogenic enzymes, which were activated by p38 and PKA signaling pathways, leading to MITF expression and CREB phosphorylation.
Highlights
Melanin is synthesized in the melanosomes of melanocytes in the basal layer of the skin epidermis [1,2]
The results suggest that LQ and LQG enhance melanin synthesis by upregulating the expression of melanogenic enzymes, which were activated by p38 and protein kinase A (PKA) signaling pathways, leading to microphthalmia-associated transcription factor (MITF)
We demonstrated that LQ and LQG have the property of melanin induction in phosphorylation and MITF expression, leading to melanogenesis [8,46,53,54,55]
Summary
Melanin is synthesized in the melanosomes of melanocytes in the basal layer of the skin epidermis [1,2]. Melanin plays an important role in determining the color of human skin and hair [1,2]. Hypopigmentation, which is the result of a reduction in melanin production in skin, causes pigmentary disorders such as vitiligo, albinism, and abnormal hair problems [5,6]. Inducers of melanin synthesis are used as tanning agents or in the treatment of hair depigmentation, and several of them are used for the treatment of pigmentary disorders, such as vitiligo [7]. Our preliminary screening identified LQ and LQG, which promote melanin synthesis in the melanoma cells. Melanin contents, intracellular tyrosinase activity, and cell viability were evaluated. Results: LQ and LQG activated melanin synthesis and intracellular tyrosinase activity
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