Background: Isoquercitrin (IQ), a flavonoid with anticancer, antioxidant, anti-inflammatory, and antiallergic properties, exhibits dual effects on B16F10 melanoma cells by suppressing cell viability and inducing hyperpigmentation. This study investigated the molecular mechanisms underlying IQ-induced melanogenesis in vitro and in vivo, highlighting the potential of IQ in the treatment of vitiligo. Methods: B16F10 melanoma cells and zebrafish were treated with various IQ concentrations and melanogenesis was evaluated using western blotting, a tyrosinase activity assay, and microscopic observation. In addition, signaling pathway modulators and IQ were used to confirm the signaling pathways involved in IQ-induced melanogenesis. Results: IQ treatment of B16F10 melanoma cells enhanced tyrosinase activity and upregulated melanogenesis-associated proteins, including microphthalmia-associated transcription factor and tyrosinase, via the p38 and protein kinase A (PKA)/cyclic AMP response element-binding protein (CREB) signaling pathways. Cotreatment with pathway-specific inhibitors (SB203580 for p38 and H89 for PKA/CREB) attenuated melanogenesis, whereas forskolin (a PKA/CREB activator) enhanced melanogenesis, confirming the involvement of these signaling pathways. In zebrafish, IQ treatment significantly increased melanophore production in the dorsal region following hypopigmentation induction with 1-phenyl-2-thiourea. Similar to that in B16F10 melanoma cells, SB203580 and H89 suppressed IQ-induced pigmentation, whereas forskolin enhanced it. Conclusion These findings demonstrate that IQ promotes melanogenesis in vitro and in vivo through activation of the p38 and PKA/CREB signaling pathways, supporting its potential as a therapeutic agent for vitiligo.

Loss of posterior bite support might cause unstable occlusal relationship and when the mandible slides forward in the centric or habitual occlusion, excessive load is applied to the anterior region followed by causing the occlusal plane to collapse or leading to a decrease in occlusal vertical dimension. In addition, disorder of temporomandibular joint function may occur. The inter-dental arch discrepancy causes a mismatch in the vertical and horizontal overlap of the anterior and posterior regions. The deep bite in the anterior region and the scissor bite in the posterior region cause unstable occlusal contact and insufficient occlusal contact area. This report was to rehabilitate a patient with above-mentioned complex problems. Physiologic adaptation to increased vertical dimension and new occlusal plane were evaluated using provisional prostheses, and definitive prostheses was fabricated using cross-mounting technique. Stable occlusion, harmonious teeth overlap and adequate occlusal plane were established, so functionally and aesthetically satisfactory results are obtained.