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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Experimental Pharmacology and Drug Discovery

Donkey Milk-derived Exosomes Protect Against UVB Irradiation-Induced Ferroptosis in Skin Cells: In Vitro and In Vivo Evidence

Provisionally accepted
Hang  TieHang Tie1*Jie  YuJie Yu2Jie  ChengJie Cheng2Guangyuan  LiuGuangyuan Liu2Zhijie  ChengZhijie Cheng2Pengxiang  NiuPengxiang Niu3Derui  XuDerui Xu3Xinyun  PeiXinyun Pei3Cong  WangCong Wang1
  • 1Chinese Academy of Inspection & Quarantine Greater Bay Area, Zhongshan, Guangdong, People's Republic of China, Zhongshan, China
  • 2Dong E E Jiao Co Ltd, Liaocheng, China
  • 3Tianjin Normal University, Tianjin, China

The final, formatted version of the article will be published soon.

UVB irradiation can induce ferroptosis and accelerates skin photoaging. However, the role of donkey milk-derived exosomes (DM-Exos) on UVB induced ferroptosis was unclear. In this study, using HaCaT keratinocytes and CCC-ESF-1 fibroblasts exposed to UVB irradiation (60–100 mJ/cm²), we found that UVB irradiation significantly reduced skin cell viability, while DM-Exos treatment effectively reversed this decline. To investigate the underlying mechanism, we assessed key markers of ferroptosis, including ROS, lipid peroxides (LipoROS), malondialdehyde (MDA), glutathione (GSH), 4-hydroxynonenal (4-HNE), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) and the results showed that UVB irradiation increased the levels of ferroptosis-related biomarkers. DM-Exos treatment reversed these changes, suggesting its role in mitigating ferroptosis. Furthermore, in a UVB-induced photoaging mouse model, subcutaneous administration of DM-Exos ameliorated skin damage, improved hydration, and reduced ferroptosis biomarkers in dorsal skin. These findings establish DM-Exos as a novel biological agent against UVB-induced skin injury and delineate a previously unrecognized mechanism linking milk-derived exosomes to ferroptosis regulation.

Keywords: donkey milk-derived exosomes, ferroptosis, ROS, Skin damage, UVB

Received: 12 Aug 2025; Accepted: 08 Dec 2025.

Copyright: © 2025 Tie, Yu, Cheng, Liu, Cheng, Niu, Xu, Pei and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hang Tie

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