Chronic exposure to inorganic arsenic is a major environmental public health issue worldwide affecting more than 220 million of people. Previous studies have shown the correlation between arsenic poisoning and cellular senescence; however, knowledge regarding the mechanism and effective prevention measures has not been fully studied. First, the associations among the ERK/CEBPB signaling pathway, oxidative stress, and arsenic-induced skin cell senescence were confirmed using the HaCaT cell model. In the arsenic-exposed group, the relative mRNA and protein expressions of ERK/CEBPB signaling pathway indicators (ERK1, ERK2, and CEBPB), cell cycle-related genes (p21, p16^INK4a), and the secretion of SASP (IL-1α, IL-6, IL-8, TGF-β1, MMP-1, MMP-3, EGF, and VEGF) and the lipid peroxidation product (MDA) were significantly increased in cells (), while the activity of antioxidant enzyme (SOD, GSH-Px, and CAT) was significantly decreased (), and an increased number of cells accumulated in the G1 phase (). Further Kaji-ichigoside F1 intervention experiments showed that compared to that in the arsenic-exposed group, the expression level of the activity of antioxidant enzyme was significantly increased in the Kaji-ichigoside F1 intervention group (), but the indicators of ERK/CEBPB signaling pathway, cell cycle-related genes, and SASP were significantly decreased (), and the cell cycle arrest relieved to a certain extent (). Our study provides some limited evidence that the ERK/CEBPB signaling pathway is involved in low-dose arsenic-induced skin cell senescence, through regulating oxidative stress. The second major finding was that Kaji-ichigoside F1 can downregulate the ERK/CEBPB signaling pathway and regulate the balance between oxidation and antioxidation, alleviating arsenic-induced skin cell senescence. This study provides experimental evidence for further understanding of Kaji-ichigoside F1, a natural medicinal plant that may be more effective in preventing and controlling arsenic poisoning.

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评估 Kaji-Ichigoside F1 对亚砷酸盐诱导的皮肤细胞衰老的潜在价值和机制

长期接触无机砷是全球影响超过 2.2 亿人的主要环境公共卫生问题。以前的研究表明砷中毒与细胞衰老之间存在相关性；然而，有关机制和有效预防措施的知识尚未得到充分研究。首先，使用 HaCaT 细胞模型证实了 ERK/CEBPB 信号通路、氧化应激和砷诱导的皮肤细胞衰老之间的关联。砷暴露组ERK/CEBPB信号通路指标（ERK1、ERK2、CEBPB）、细胞周期相关基因（p21、p16 ^INK4a）、SASP（IL-1 α、IL-6、IL-8、TGF-β1、MMP-1、MMP-3、EGF 和 VEGF）和脂质过氧化产物（MDA）在细胞中显着增加（），而抗氧化酶（SOD、GSH-Px 和 CAT）的活性显着降低（），并且在 G1 期积累的细胞数量增加（）。进一步的Kaji-ichigoside F1干预实验表明，与砷暴露组相比， Kaji-ichigoside F1干预组），但ERK/CEBPB信号通路、细胞周期相关基因、SASP等指标显着下降（），细胞周期停滞在一定程度上得到缓解（）。我们的研究提供了一些有限的证据表明 ERK/CEBPB 信号通路通过调节氧化应激参与了低剂量砷诱导的皮肤细胞衰老。第二个主要发现是Kaji-ichigoside F1可以下调 ERK/CEBPB 信号通路，调节氧化和抗氧化之间的平衡，缓解砷诱导的皮肤细胞衰老。本研究为进一步认识可能更有效防治砷中毒的天然药用植物栀子苷F1提供了实验证据。