Ginsenosides exhibit potential therapeutic potential in photoaging by regulating keratinocyte ferroptosis

IF 7.5 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2026-05-01 Epub Date: 2025-11-05 DOI:10.1016/j.jgr.2025.11.002

Lulu Tang , Xianjie Chen , Keyue Chen , Xinlei Zheng , Min Ye , Zhongqiu Liu , Wang Li , Xiaoyi Liu

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引用次数: 0

Abstract

Background

Skin photoaging is a chronic inflammatory state induced by ultraviolet (UV) radiation. Ferroptosis has recently emerged as a critical mechanism implicated in the pathogenesis of photoaging. Ginsenosides, active compounds in ginseng, hold potential for treating skin photoaging, but their molecular mechanisms in regulating ferroptosis remain unclear.

Methods

We utilized single-cell RNA sequencing (scRNA-seq) to analyze murine skin after UVB irradiation, focusing on keratinocyte subpopulations and ferroptosis-related genes. Molecular docking assessed ginsenoside binding to ferroptosis regulators. Embryotoxicity of ginsenosides was evaluated using zebrafish embryos. Ferroptosis gene expression in UVB-exposed keratinocytes with or without ginsenoside treatment was analyzed by Western blot and RT-qPCR.

Results

scRNA-seq revealed a significant increase in keratinocyte numbers and ferroptosis signals following UVB irradiation. We observed that UVB exposure reduced SLC7A11 and GPX4 expression while increasing HMGB1 in keratinocytes. Molecular docking experiments further indicated that ginsenosides C-K and C-Mc can target ferroptosis-related proteins, and are non-toxic in zebrafish embryos. Treatment with ginsenosides effectively attenuated skin photoaging by modulating the SLC7A11/GPX4 axis and suppressing HMGB1 expression, thereby reducing UVB-induced reactive oxygen species levels and restoring keratinocyte viability. Additionally, we also identified three differentiation trajectories of keratinocytes and found that bone marrow-derived cell Gas6 signaling may influence ferroptosis via the Axl/Tyro3 pathway.

Conclusion

Our findings suggest that ginsenosides may represent promising therapeutic candidates for alleviating UVB-induced skin photoaging via modulation of the ferroptosis-associated SLC7A11/GPX4 axis and HMGB1 expression, providing novel mechanistic insights and therapeutic strategies against skin photoaging.

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人参皂苷通过调节角化细胞铁下垂在光老化中表现出潜在的治疗潜力

皮肤光老化是一种由紫外线辐射引起的慢性炎症状态。铁下垂最近被认为是光老化发病机制中的一个关键机制。人参皂苷是人参中的活性物质，具有治疗皮肤光老化的潜力，但其调控铁下垂的分子机制尚不清楚。方法采用单细胞RNA测序（scRNA-seq）技术对UVB照射后小鼠皮肤进行分析，重点分析角化细胞亚群和凋亡相关基因。分子对接评估了人参皂苷与铁下垂调节因子的结合。用斑马鱼胚胎评价了人参皂苷的胚胎毒性。采用Western blot和RT-qPCR分析uvb暴露的角质形成细胞在人参皂苷处理或不处理下的凋亡基因表达。结果scrna -seq结果显示，UVB照射后角质形成细胞数量和铁凋亡信号明显增加。我们观察到UVB暴露降低了角化细胞中SLC7A11和GPX4的表达，同时增加了HMGB1的表达。分子对接实验进一步表明，人参皂苷C-K和C-Mc可以靶向铁中毒相关蛋白，且对斑马鱼胚胎无毒。人参皂苷通过调节SLC7A11/GPX4轴和抑制HMGB1表达，有效地减缓皮肤光老化，从而降低uvb诱导的活性氧水平，恢复角质细胞活力。此外，我们还确定了角质形成细胞的三种分化轨迹，并发现骨髓源性细胞Gas6信号可能通过Axl/Tyro3途径影响铁凋亡。结论人参皂苷可能通过调控死铁相关的SLC7A11/GPX4轴和HMGB1表达来缓解uvb诱导的皮肤光老化，为皮肤光老化提供了新的机制见解和治疗策略。

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来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.