The Anti-Vitiligo Effects of Feshurin In Vitro from Ferula samarcandica and the Mechanism of Action.

BACKGROUND: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves ß-catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. Ferula has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented. METHODS: CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1. RESULTS: The sesquiterpene coumarin feshurin was separated from Ferula samarcandica. Feshurin was shown to induce GSK-3ß phosphorylation, resulting in the translocation of ß-catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking. CONCLUSIONS: Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics.

Quercetin 3-O-(6″-O-E-caffeoyl)-ß-D-glucopyranoside, a Flavonoid Compound, Promotes Melanogenesis through the Upregulation of MAPKs and Akt/GSK3ß/ß-Catenin Signaling Pathways.

Quercetin 3-O-(6″-O-E-caffeoyl)-ß-D-glucopyranoside is a flavonoid compound produced by various plants with reported antiprotozoal potential against E. histolytica and G. lamblia; however, its effects on skin pigment regulation have not been studied in detail. In this investigation, we discovered that quercetin 3-O-(6″-O-E-caffeoyl)-D-glucopyranoside (coded as CC7) demonstrated a more increased melanogenesis effect in B16 cells. CC7 exhibited no cytotoxicity or effective stimulating melanin content or intracellular tyrosinase activity. This melanogenic-promoting effect was accompanied by activated expression levels of microphthalmia-associated transcription factor (MITF), a key melanogenic regulatory factor, melanogenic enzymes, and tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) and 2 (TRP-2) in the CC7-treated cells. Mechanistically, we found that CC7 exerted melanogenic effects by upregulating the phosphorylation of stress-regulated protein kinase (p38) and c-Jun N-terminal kinase (JNK). Moreover, the CC7 upregulation of phosphor-protein kinase B (Akt) and Glycogen synthase kinase-3 beta (GSK-3ß) increased the content of ß-catenin in the cell cytoplasm, and subsequently, it translocated into the nucleus, resulting in melanogenesis. Specific inhibitors of P38, JNK, and Akt validated that CC7 promotes melanin synthesis and tyrosinase activity by regulating the GSK3ß/ß-catenin signaling pathways. Our results support that the CC7 regulation of melanogenesis involves MAPKs and Akt/GSK3ß/ß-catenin signaling pathways.

Chemical constituents of Ruta graveolens L. and their melanogenic effects and action mechanism.

Ruta graveolens L. has been widely used to treat various skin ailments, especially vitiligo. In this study, we isolated a new furanocoumarin named Rutagrarin (1) along with 14 known compounds (2-15) from the aerial parts of R. graveolens and elucidated their chemical structures via various spectroscopy. We found that compound 5 promoted melanogenesis and tyrosinase activity in B16 cells. Further investigation on underlying mechanisms revealed that compound 5 activated the transcription of microtia-related transcription factors and promoted the production of melanin in B16 cells via the Akt/GSK-3ß/ß-catenin pathway. Therefore, we confirmed the traditional efficacy of R. graveolens and speculated that compound 5 could be used as a natural drug to treat vitiligo.