Casearia sylvestris extract and hymenaea courbaril extract (Jatobá) suppresses UVB inducted premature cellular senescence in human dermal fibroblasts

Summary: Abstract Body: The skin is the organ constantly exposed to various stimuli that influences its morphology and function. Skin aging can be categorized as intrinsic, a natural process driven by chronological time, and extrinsic, influenced by environmental factors such as sun exposure. UV radiation is the primary accelerator of premature aging, causing oxidative damage and DNA harm, which induces cellular senescence. Senescent cells are characterized by reduced proliferation, resistance to apoptosis, and the secretion of factors that promote inflammation and tissue deterioration, known as senescence-associated secretory phenotype (SASP). These cells accumulate with age, contributing to the changes in the skin associated with aging. The SASP plays a pivotal role in chronic skin inflammation, as it exhibits a modified secretome that includes pro-inflammatory cytokines, chemokines, proteinases, and growth factors, which significantly alter the skin microenvironment. In the present study, 44 molecular targets were evaluated for their capacity to identify the senescent state in prematurely aged cells. Primary human dermal fibroblasts were irradiated for 4 consecutive days with UVB radiation, totaling 1J/cm2. A real-time RT-PCR assay, followed by protein quantification, was conducted to assess the potential of the ingredients in preventing premature senescence within this in vitro model. Gene expression analysis was performed using IPA (Ingenuity Pathway Analysis) software, and the activation of biological pathways was evaluated. The results demonstrated that the Casearia and Jatobá extracts effectively inhibited the activation of the Senescence pathway, as well as the signaling pathways of IL6, IL8, and STAT3, by suppressing the gene expression of their key markers: CDKN1A, CDKN2A, IL1α, IL1β, IL6, and IL8. This effect was corroborated by protein expression analysis, revealing a gene expression profile similar to those non-senescent cells when compared to UVB-induced senescent cells. Juliana C. Lago-Nold¹, Ana Luisa Dias¹, Melissa D. Ganzerla¹, Kelen F. Arroteia¹ 1. Natura Cosmeticos SA, Cajamar, SP, Brazil. Translational Studies: Cell and Molecular Biology