Hyperoside reduced particulate matter 2.5-induced endoplasmic reticulum stress and senescence in skin cells.

Particulate matter 2.5 (PM 2.5 ) causes skin aging, inflammation, and impaired skin homeostasis. Hyperoside, a flavanol glycoside, has been proposed to reduce the risk of diseases caused by oxidative stress. This study evaluated the cytoprotective potential of hyperoside against PM 2.5 -induced skin cell damage. Cultured human HaCaT keratinocytes were pretreated with hyperoside and treated with PM 2.5 . Initially, the cytoprotective and antioxidant ability of hyperoside against PM 2.5 was evaluated. Western blotting was further employed to investigate endoplasmic reticulum (ER) stress and cellular senescence and for evaluation of cell cycle regulation-related proteins. Hyperoside inhibited PM 2.5 -mediated ER stress as well as mitochondrial damage. Colony formation assessment confirmed that PM 2.5 -impaired cell proliferation was restored by hyperoside. Moreover, hyperoside reduced the activation of PM 2.5 -induced ER stress-related proteins, such as protein kinase R-like ER kinase, cleaved activating transcription factor 6, and inositol-requiring enzyme 1. Hyperoside promoted cell cycle progression in the G 0 /G 1 phase by upregulating the PM 2.5 -impaired cell cycle regulatory proteins. Hyperoside significantly reduced the expression of PM 2.5 -induced senescence-associated β-galactosidase and matrix metalloproteinases (MMPs), such as MMP-1 and MMP-9. Overall, hyperoside ameliorated PM 2.5 -impaired cell proliferation, ER stress, and cellular senescence, offering potential therapeutic implications for mitigating the adverse effects of environmental pollutants on skin health.