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. 2022 Jan 11:2022:9574473.
doi: 10.1155/2022/9574473. eCollection 2022.

Assessing the Potential Value and Mechanism of Kaji-Ichigoside F1 on Arsenite-Induced Skin Cell Senescence

Affiliations

Assessing the Potential Value and Mechanism of Kaji-Ichigoside F1 on Arsenite-Induced Skin Cell Senescence

Qibing Zeng et al. Oxid Med Cell Longev. .

Abstract

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, p16INK4a), 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 (P < 0.05), while the activity of antioxidant enzyme (SOD, GSH-Px, and CAT) was significantly decreased (P < 0.05), and an increased number of cells accumulated in the G1 phase (P < 0.05). 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 (P < 0.05), but the indicators of ERK/CEBPB signaling pathway, cell cycle-related genes, and SASP were significantly decreased (P < 0.05), and the cell cycle arrest relieved to a certain extent (P < 0.05). 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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Conflict of interest statement

The authors declare that they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Arsenic can induce the skin cell senescence by promoting the level of SASP secretion and cell cycle arrest in cells. The in vitro results were based on 6 independent experiments. All data are presented as mean ± standard deviation. P < 0.05. (a) The concentration of inflammatory factors. (b) The concentration of matrix remodeling factors and growth factors. (c) The cell cycle for each group. (d) The cell cycle analysis of flow cytometry. (e) The relative mRNA expression of p21 and p16INK4a to cell cycle regulation. (f) The relative protein expression of p21 and p16INK4a to cell cycle regulation. (g) The western blot for p21 and p16INK4a.
Figure 2
Figure 2
The ERK/CEBPB signaling pathway participates in arsenic-induced skin cell senescence through regulating oxidative stress. The in vitro results were based on 6 independent experiments. All data are presented as mean ± standard deviation. P < 0.05. (a) The relative mRNA expression of genes related to the ERK/CEBPB signaling pathway. (b) The relative protein expression related to the ERK/CEBPB signaling pathway. (c) The concentration of oxidative stress indicators. (d) The western blot for the indicators of the ERK/CEBPB signaling pathway.
Figure 3
Figure 3
Kaji-ichigoside F1 can downregulate the ERK/CEBPB signaling pathway and regulate the balance between oxidation and antioxidation, alleviating arsenic-induced skin cell senescence. The in vitro results were based on 6 independent experiments. All data are presented as mean ± standard deviation. P < 0.05. (a) The relative mRNA expression of genes related to the ERK/CEBPB signaling pathway. (b) The relative protein expression related to the ERK/CEBPB signaling pathway. (c) The relative mRNA expression of p21 and p16INK4a to cell cycle regulation. (d) The relative protein expression of p21 and p16INK4a to cell cycle regulation. (e) The concentration of SASP. (f) The cell cycle for each group. (g) The concentration of oxidative stress indicators. (h) The western blot for the indicators of the ERK/CEBPB signaling pathway. (i) The western blot for p21 and p16INK4a. (j) The cell cycle analysis of flow cytometry.
Figure 4
Figure 4
Assessing the potential value and mechanism of Kaji-ichigoside F1 on arsenite-induced skin cell senescence. Overall, 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.

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