The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation
In this study, we demonstrated that 2<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-hydro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10393 |
| _version_ | 1797594242619539456 |
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| author | Sungmin Bae Chang-Gu Hyun |
| author_facet | Sungmin Bae Chang-Gu Hyun |
| author_sort | Sungmin Bae |
| collection | DOAJ |
| description | In this study, we demonstrated that 2<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-hydroxy-3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-dimethoxychalcone (3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC) alleviated <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>-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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula> (GSK-3<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>)/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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC on macrophage RAW264.7 cells with LPS stimulation. 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC significantly inhibited LPS-stimulated nitric oxide production. 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 on the protein level. In addition, 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC decreased the production of the tumor necrosis factor-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula> and interleukin-6. Successively, our mechanistic studies revealed that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of I<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">κ</mi></semantics></math></inline-formula>B<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>, p38MAPK, ERK, and JNK. The Western blot assay results showed that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC suppresses LPS-induced p65 translocation from cytosol to the nucleus. Finally, the topical applicability of 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC was tested through primary skin irritation, and it was found that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC, at 5 and 10 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">μ</mi></semantics></math></inline-formula>M concentrations, did not cause any adverse effects. Therefore, 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC may provide a potential candidate for preventing and treating melanogenic and inflammatory skin diseases. |
| first_indexed | 2024-03-11T02:20:48Z |
| format | Article |
| id | doaj.art-e00e80f429a7499298b571cb847ceefd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:20:48Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e00e80f429a7499298b571cb847ceefd2023-11-18T10:52:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121039310.3390/ijms241210393The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and InflammationSungmin Bae0Chang-Gu Hyun1Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of KoreaJeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Republic of KoreaIn this study, we demonstrated that 2<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-hydroxy-3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-dimethoxychalcone (3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC) alleviated <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>-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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula> (GSK-3<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">β</mi></semantics></math></inline-formula>)/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<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC on macrophage RAW264.7 cells with LPS stimulation. 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC significantly inhibited LPS-stimulated nitric oxide production. 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 on the protein level. In addition, 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC decreased the production of the tumor necrosis factor-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula> and interleukin-6. Successively, our mechanistic studies revealed that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of I<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">κ</mi></semantics></math></inline-formula>B<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>, p38MAPK, ERK, and JNK. The Western blot assay results showed that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC suppresses LPS-induced p65 translocation from cytosol to the nucleus. Finally, the topical applicability of 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC was tested through primary skin irritation, and it was found that 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC, at 5 and 10 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">μ</mi></semantics></math></inline-formula>M concentrations, did not cause any adverse effects. Therefore, 3,6<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><msup><mrow></mrow><mo>′</mo></msup></semantics></math></inline-formula>-DMC may provide a potential candidate for preventing and treating melanogenic and inflammatory skin diseases.https://www.mdpi.com/1422-0067/24/12/10393B16F102′-hydroxy-3,6′-dimethoxychalconeinflammationmelanogenesisRAW 264.7 |
| spellingShingle | Sungmin Bae Chang-Gu Hyun The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation International Journal of Molecular Sciences B16F10 2′-hydroxy-3,6′-dimethoxychalcone inflammation melanogenesis RAW 264.7 |
| title | The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation |
| title_full | The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation |
| title_fullStr | The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation |
| title_full_unstemmed | The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation |
| title_short | The Effects of 2<sup>′</sup>-Hydroxy-3,6<sup>′</sup>-Dimethoxychalcone on Melanogenesis and Inflammation |
| title_sort | effects of 2 sup sup hydroxy 3 6 sup sup dimethoxychalcone on melanogenesis and inflammation |
| topic | B16F10 2′-hydroxy-3,6′-dimethoxychalcone inflammation melanogenesis RAW 264.7 |
| url | https://www.mdpi.com/1422-0067/24/12/10393 |
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