Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Caffeic Acid Protects Keratinocytes from PM2.5 by Regulating ROS, Mitochondrial Integrity, and JNK Activation

  • Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna (College of Medicine and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Mei Jing Piao (College of Medicine and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Kyoung Ah Kang (College of Medicine and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Mahadurage Pasindu Laksara Madhuwantha (College of Medicine and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Jinny Park (Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine) ;
  • Jin Won Hyun (College of Medicine and Jeju Research Center for Natural Medicine, Jeju National University)
  • Received : 2025.12.09
  • Accepted : 2026.02.12
  • Published : 2026.05.01
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Abstract

Caffeic acid (CA) is a naturally occurring phenolic compound known for its strong antioxidant and cytoprotective properties. Particulate matter (PM) with an aerodynamic diameter of 2.5 ㎛ (PM2.5) or less is a major atmospheric pollutant that induces excessive oxidative stress and apoptosis in human skin cells, contributing to various adverse effects on the skin. In this study, we investigated the protective role of CA against PM2.5-induced cellular injury in human HaCaT keratinocytes. CA reduced PM2.5-induced reactive oxygen species (ROS) accumulation and mitigated oxidative damage, including lipid peroxidation, protein carbonyl formation, mitochondrial membrane depolarization, and intracellular calcium overload. In addition, CA attenuated PM2.5-induced apoptosis by upregulating B-cell lymphoma 2 (Bcl-2) and suppressing Bcl-2-associated X protein (Bax), caspase-3, caspase-9, and phosphorylated c-Jun N-terminal kinase (phospho-JNK). Collectively, these findings demonstrate that CA protects HaCaT keratinocytes from PM2.5-induced oxidative stress and apoptosis by regulating the Bcl-2/Bax axis and inhibiting JNK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for preventing pollutant-induced skin damage.

Keywords

Acknowledgement

This research was funded by the National Research Foundation of Korea (NRF) through the Basic Science Research Program, under the Ministry of Education (RS-2023-00270936).

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