The Effects of 2 ' -Hydroxy-3,6 ' -Dimethoxychalcone on Melanogenesis and Inflammation

• Published in: International journal of molecular sciences 2023-06, Vol.24 (12), p.10393
• Main Authors: Bae, Sungmin, Hyun, Chang-Gu
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 2′-hydroxy-3,6′-dimethoxychalcone; AKT protein; Analysis; Animals; B16F10; c-Jun protein; Cyclooxygenase-2; Cytosol; Cytotoxicity; Down-regulation; Enzymes; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Glycogens; Inflammation; Interleukin 6; Intermedin; Investigations; Irritation; JNK protein; Kinases; Lipopolysaccharides; Lipopolysaccharides - toxicity; Macrophages; Melanin; Melanins - metabolism; melanogenesis; Melanoma; Mice; Microphthalmia-associated transcription factor; Monophenol Monooxygenase - metabolism; Natural products; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Polyphenols; Prostaglandin endoperoxide synthase; Protein expression; Protein kinase A; Protein kinases; Proteins; Radiation; RAW 264.7; Skin; Skin diseases; Skin tests; Synthesis; Transcription factors; Tyrosinase; Tyrosinase-related protein 1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241210393

In this study, we demonstrated that 2'-hydroxy-3,6'-dimethoxychalcone (3,6'-DMC) alleviated α-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-3β (GSK-3β)/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-α and interleukin-6. Successively, our mechanistic studies revealed that 3,6'-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of IκBα, 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 μM 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.