Zhang Ziwei, Yang Pu, Sun Yang, Yu Xinhai, Chen Xiangyu, Wang Xiancheng
Medical Aesthetics Department, Changsha Maternal and Child Health Hospital, Changsha, Hunan, 410000, People's Republic of China.
Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People's Republic of China.
Clin Cosmet Investig Dermatol. 2025 Aug 20;18:1971-1983. doi: 10.2147/CCID.S523963. eCollection 2025.
This research seeks to explore the impact of Ellagic Acid (EA) on the aging process of human dermal fibroblasts Hs68 cells and to uncover the mechanisms involved.
Senescence was induced in Hs68 cells with HO, followed by treatment with EA and CSNK2A1 inhibitor (Silmitasertib). Bioinformatics identified EA's downstream targets. Cell viability was assessed by MTT assays, and senescence markers (γH2AX, p16, p19, p53), CSNK2A1, Nrf2, and NF-κB p65 were analyzed by Western blot. Inflammatory cytokines (IL-6, TNF-α, IL-1β) and oxidative stress markers (SOD, MDA, GSH/GSSG) were measured. ROS levels were assessed by fluorescence staining, senescence by SA-β-gal staining, cell cycle by flow cytometry and apoptosis by TUNEL assay.
Senescent cells showed increased γH2AX, p16, p19, and p53 expression, with reduced viability. EA inhibited senescence in a dose-dependent manner, with cytotoxicity at 60 μM. EA upregulated CSNK2A1, decreased β-galactosidase activity, restored cell viability and cycle progression, and reduced apoptosis. EA alleviated oxidative stress by enhancing Nrf2 expression, reducing ROS and MDA, and increasing SOD and GSH/GSSG. Silmitasertib negated these effects. EA also reduced IL-6, TNF-α, and IL-1β, inhibiting NF-κB p65, with anti-inflammatory effects mediated by CSNK2A1.
EA delays dermal fibroblast senescence by modulating CSNK2A1, mitigating oxidative stress and inflammation, and may serve as a potential therapeutic for aging and age-related diseases.
本研究旨在探讨鞣花酸（EA）对人皮肤成纤维细胞Hs68细胞衰老过程的影响，并揭示其中涉及的机制。
用HO诱导Hs68细胞衰老，然后用EA和CSNK2A1抑制剂（西美替尼）处理。生物信息学鉴定了EA的下游靶点。通过MTT法评估细胞活力，通过蛋白质免疫印迹法分析衰老标志物（γH2AX、p16、p19、p53）、CSNK2A1、Nrf2和NF-κB p65。检测炎性细胞因子（IL-6、TNF-α、IL-1β）和氧化应激标志物（SOD、MDA、GSH/GSSG）。通过荧光染色评估ROS水平，通过SA-β-半乳糖苷酶染色评估衰老，通过流式细胞术分析细胞周期，通过TUNEL法检测细胞凋亡。
衰老细胞中γH2AX、p16、p19和p53表达增加，活力降低。EA以剂量依赖性方式抑制衰老，60μM时具有细胞毒性。EA上调CSNK2A1，降低β-半乳糖苷酶活性，恢复细胞活力和细胞周期进程，并减少细胞凋亡。EA通过增强Nrf2表达、降低ROS和MDA以及增加SOD和GSH/GSSG来减轻氧化应激。西美替尼消除了这些作用。EA还降低了IL-6、TNF-α和IL-1β，抑制NF-κB p65，其抗炎作用由CSNK2A1介导。
EA通过调节CSNK2A1、减轻氧化应激和炎症来延缓皮肤成纤维细胞衰老，可能成为衰老及衰老相关疾病的潜在治疗药物。
