Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo

  • Mei Jing Piao (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Pattage Madushan Dilhara Jayatissa Fernando (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Kyoung Ah Kang (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Pincha Devage Sameera Madushan Fernando (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Herath Mudiyanselage Udari Lakmini Herath (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University) ;
  • Young Ree Kim (Department of Laboratory Medicine, Jeju National University Hospital, and College of Medicine, Jeju National University) ;
  • Jin Won Hyun (Department of Biochemistry, College of Medicine, and Jeju Research Center for Natural Medicine, Jeju National University)
  • Received : 2023.10.13
  • Accepted : 2023.11.16
  • Published : 2024.01.01
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Abstract

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2023-00270936). This work was supported by a research grant from Jeju National University Hospital in 2023.

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