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Paeonol Attenuates UVB-Induced Premature Senescence in Human Dermal Fibroblasts to Promote Skin Longevity

Year: 2026

Type: article

Abstract: Skin photoaging is largely driven by ultraviolet (UV) irradiation, which contributes to chronic inflammation and extracellular matrix (ECM) degradation. This study investigated the protective effects of paeonol against UVB-induced cellular senescence in human dermal fibroblasts (HDFn). Repeated UVB irradiation was used to induce premature senescence. Paeonol treatment reduced the senescence-associated β-galactosidase (SA-β-gal) positive cells and intracellular reactive oxygen species (ROS) accumulation. Paeonol also reduced the expression of senescence-associated cell cycle regulators, including p21 and p16 at the mRNA level and the protein level. In addition, paeonol suppressed matrix metalloproteinase-1 (MMP-1) production but did not significantly restore type I procollagen secretion. Paeonol also attenuated the expression and secretion of the senescence-associated secretory phenotype (SASP) factors inter-leukin-6 (IL-6) and interleukin-8 (IL-8). These effects were accompanied by reduced phosphorylation of JNK and c-Jun. Furthermore, activation of JNK signaling with anisomycin partially reversed the paeonol-mediated suppression of MMP-1 mRNA expression, supporting the involvement of JNK signaling in the regulation of MMP-1. Collectively, these findings suggest that paeonol attenuates multiple features of UVB-induced cellular senescence in HDFn cells, with JNK signaling potentially contributing to its inhibitory effect on MMP-1 expression. Further studies are needed to clarify the mechanisms underlying these effects and establish their physiological relevance in UVA-based and in vivo models.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27209352