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

Abstract

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 G₀/G₁ 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.