Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the destruction of melanocytes or obstruction of the melanin synthesis pathway. Melanin is a type of skin pigment that determines skin color. The seeds of Vernonia anthelmintica (L.) Willd (Kaliziri) are used for treating skin diseases including vitiligo in traditional Uyghur medicine. 1,5-Dicaffeoylquinic acid (1,5-diCQA) is a natural polyphenolic compound widely distributed in plants and extracted from Kaliziri seeds. Therefore, in the present study, the effect of 1,5-diCQA on melanin synthesis in B16 cell was evaluated, and its molecular mechanism was explored. The results indicated that 1,5-diCQA treatment of B16 cells stimulated an increase of intracellular melanin level and tyrosinase (TYR) activity without cytotoxicity. Reverse transcription quantitative polymerase chain reaction results also indicated that 1,5-diCQA may markedly improve the protein expression and RNA transcription of microphthalmia-associated transcription factor (MITF), melanogenic enzyme Tyr, tyrosinase-related protein 1 (TRP 1) and tyrosinase-related protein 2 (TRP 2). Additional results identified that 1,5-diCQA may promote the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) MAPK. Notably, the increased levels of intracellular melanin synthesis and tyrosinase expression induced by 1,5-diCQA treatment were significantly attenuated by the protein kinase A (PKA) inhibitor H-89. Intracellular cyclic adenosine monophosphate (cAMP) concentration and phosphorylation of cAMP-response element binding protein was increased following 1,5-diCQA treatment. These results indicated that 1,5-diCQA stimulated melanogenesis via the MAPK and cAMP/PKA signaling pathways in B16 cells, which has potential therapeutic implications for vitiligo.

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Isochlorogenic acid A, also called 3,5-dicaffeoylquinic acid (3,5-diCQA), is a widespread phenolic compound in the plant. Recent studies have shown that it has antioxidant and anti-inflammatory activity. In addition, oxidative stress and inflammation induced by solar ultraviolet radiation is a very significant reason for skin depigmentation. Therefore, in this study, we evaluated the effect of 3,5-diCQA on B16 cells and explored its molecular mechanism. Results showed that 3,5-diCQA upregulated intracellular melanin production in a time- and dose-dependent manner. Tyrosinase (TYR) activity was also increased after treatment with 3,5-diCQA in a dose-dependent manner. Expressions of TYR, TYR-related protein1, TYR-related protein2, and microphthalmia-associated transcription factor were upregulated in a dose-dependent manner after 48 h of treatment with 3,5-diCQA. Results also showed that 3,5-diCQA promoted the phosphorylation of Akt at Thr308 and glycogen synthase kinase-3β at Ser 9. Moreover, 3,5-diCQA increased the content of β-catenin in cell cytoplasm and nucleus by reducing the content of phosphorylated β-catenin (p-β-catenin). All these results suggest that 3,5-diCQA may mediate the acceleration of melanin synthesis by the β-catenin signal pathway.

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