Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matter

Shikonin, an herbal naphthoquinone, demonstrates a broad spectrum of pharmacological properties. Owing to increasingly adverse environmental conditions, human skin is vulnerable to harmful influences from dust particles. This study explored the antioxidant capabilities of shikonin and its ability to protect human keratinocytes from oxidative stress induced by fine particulate matter (PM_2.5). We found that shikonin at a concentration of 3 µM was nontoxic to human keratinocytes and effectively scavenged reactive oxygen species (ROS) while increasing the production of reduced glutathione (GSH). Furthermore, shikonin enhanced GSH level by upregulating glutamate-cysteine ligase catalytic subunit and glutathione synthetase mediated by nuclear factor-erythroid 2-related factor. Shikonin reduced ROS levels induced by PM_2.5, leading to recovering PM_2.5-impaired cellular biomolecules and cell viability. Shikonin restored the GSH level in PM_2.5-exposed keratinocytes via enhancing the expression of GSH-synthesizing enzymes. Notably, buthionine sulphoximine, an inhibitor of GSH synthesis, diminished effect of shikonin against PM_2.5-induced cell damage, confirming the role of GSH in shikonin-induced cytoprotection. Collectively, these findings indicated that shikonin could provide substantial cytoprotection against the adverse effects of PM_2.5 through direct ROS scavenging and modulation of cellular antioxidant system.