In this study, we demonstrated that 2
-hydroxy-3,6
-dimethoxychalcone (3,6
-DMC) alleviated
-MSH-induced melanogenesis and lipopolysaccharides (LPS)-induced inflammation in mouse B16F10 and RAW 264.7 cells. In vitro analysis results showed that the melanin content and intracellular tyrosinase activity were significantly decreased by 3,6
-DMC, without cytotoxicity, via decreases in tyrosinase and the tyrosinase-related protein 1 (TRP-1) and TRP-2 melanogenic proteins, as well as the downregulation of microphthalmia-associated transcription factor (MITF) expression through the upregulation of the phosphorylation of extracellular-signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3
(GSK-3
)/catenin, and downregulation of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and protein kinase A (PKA). Furthermore, we investigated the effect of 3,6
-DMC on macrophage RAW264.7 cells with LPS stimulation. 3,6
-DMC significantly inhibited LPS-stimulated nitric oxide production. 3,6
-DMC also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 on the protein level. In addition, 3,6
-DMC decreased the production of the tumor necrosis factor-
and interleukin-6. Successively, our mechanistic studies revealed that 3,6
-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of I
B
, p38MAPK, ERK, and JNK. The Western blot assay results showed that 3,6
-DMC suppresses LPS-induced p65 translocation from cytosol to the nucleus. Finally, the topical applicability of 3,6
-DMC was tested through primary skin irritation, and it was found that 3,6
-DMC, at 5 and 10
M concentrations, did not cause any adverse effects. Therefore, 3,6
-DMC may provide a potential candidate for preventing and treating melanogenic and inflammatory skin diseases.
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