Study on the Mechanism of Paeoniflorin, an Active Component of Paeonia lactiflora Pall., in Improving Skin Pigmentation by Inhibiting the TNF-α Signaling Pathway

<b>Background/Objectives</b>: This article employs both in vivo and in vitro experiments. <b>Methods</b>: The core targets and key pathways of <i>Paeoniflorin</i> were predicted using a PPI network analysis, GO analysis, and KEGG analysis. Subsequently, molecular docking analysis and molecular simulation dynamics were performed on the core effector. In vitro experiments employed a UVB-irradiated B16F10 cell model. The effects of Paeoniflorin on melanin content and tyrosinase activity were evaluated. Apoptosis and inflammatory cytokine levels were also assessed in vitro. In vivo experiments used a model combining progesterone injection with UV irradiation. Histopathological skin changes and melanin granule distribution were examined using HE staining. Skin melanin content, tyrosinase activity, and expression levels of related proteins were measured. Additionally, ELISA assays measured serum IL-6 and TNF-α inflammatory cytokines in mice. <b>Results</b>: Rese screening identified 69 targets involved in Paeoniflorin's effects on melanogenesis, including TNF-α, IL-6, TP53, MAPK3, HIF1A and BCL2. Molecular docking and molecular dynamics simulations indicate that Paeoniflorin exhibits strong affinity for tumor necrosis factor-α. In in vitro experiments, Paeoniflorin significantly reduced UVB-induced melanin content and tyrosinase activity in B16F10 cells. It also promoted melanocyte apoptosis and a dose-dependent decrease in IL-6 and TNF-α levels. In vivo, Paeoniflorin significantly reduced epidermal and dermal thickness and inhibited inflammatory infiltration. It decreased melanin granules, melanin content, tyrosinase activity, and IL-6 and TNF-α levels in mouse skin tissue. <b>Conclusions</b>: This research indicates that Paeoniflorin can significantly suppress UVB-induced cellular inflammatory responses by inhibiting the TNF signaling pathway, thereby reducing hyperpigmentation.