Perilla Frutescens leaf-derived exosome-like nanoparticles inhibit ferroptosis in epidermal keratinocytes

Summary: Abstract Body: Plant-derived exosome-like nanoparticles (PDEN) are nano-sized particles extracted from plant cells and are generally composed of proteins, lipids, nucleic acids, and other potential signaling components. Recently, various biological functions such as antioxidant, anti-inflammatory, and immune regulation have been reported for PDENs, along with their low toxicity and high safety profiles. Ferroptosis is a recently identified regulated cell death mechanism characterized by iron ion accumulation and lipid peroxidation. The potential involvement of ferroptosis in various skin diseases and aging processes suggests the potential benefits of ferroptosis inhibitors on skin health. In this study, we examined the inhibitory activity of PDENs on ferroptosis in cultured human epidermal keratinocytes (HaCaT). Treatment with RSL3, a potent inhibitor of glutathione peroxidase 4 (GPX4)-induced ferroptosis, induced significant cytotoxicity in HaCaT cells, and among the various PDENs tested, Perilla frutescens PDENs significantly prevented cell death. Further investigation suggested that changes in antioxidant-related factor expression and lipid peroxidation-related enzyme expression underlie the inhibitory effects of Perilla frutescens PDENs on RSL-3-induced ferroptosis. These results suggest that PDENs have potential as natural product-based therapeutics and cosmetic materials for protecting skin cells against ferroptosis. MyungHo Kor¹, Sekyoo Jeong¹, Hyunjung Kim² 1. Incospharm, Daejeon, Daejeon, Korea (the Republic of). 2. Chungnam National University Sejong Hospital, Sejong, Sejong, Korea (the Republic of). Cell Communication Networks and Stromal Biology