Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes

Particulate matter 2.5 (PM2.5) exposure can trigger adverse health outcomes in the human skin, such as skin aging, wrinkles, pigment spots, and atopic dermatitis. PM2.5 is associated with mitochondrial damage and the generation of reactive oxygen species (ROS). Hesperidin is a bioflavonoid that exhibits antioxidant and anti-inflammatory properties. This study aimed to determine the mechanism underlying the protective effect of hesperidin on human HaCaT keratinocytes against PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence. Human HaCaT keratinocytes were pre-treated with hesperidin and then treated with PM2.5. Hesperidin attenuated PM2.5-induced mitochondrial and DNA damage, G(0)/G(1) cell cycle arrest, and SA-beta Gal activity, the protein levels of cell cycle regulators, and matrix metalloproteinases (MMPs). Moreover, treatment with a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, along with hesperidin markedly restored PM2.5-induced cell cycle arrest and cellular senescence. In addition, hesperidin significantly reduced the activation of MMPs, including MMP-1, MMP-2, and MMP-9, by inhibiting the activation of activator protein 1. In conclusion, hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence in human HaCaT keratinocytes via the ROS/JNK pathway.

Automated summary

This study revealed that hesperidin exhibits a protective effect on human HaCaT keratinocytes against PM2.5-induced cellular damage, cell cycle arrest, and cellular senescence. Hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence through the ROS/JNK pathway, and inhibits the activation of matrix metalloproteinases by suppressing activator protein 1 activation.