P-Hydroxybenzaldehyde from Gastrodia elata Blume Reduces Hydroxyurea-Induced Cellular Senescent Phenotypes in Human SH-SY5Y Cells via Enhancing Autophagy

<b>Background/Objectives</b>: The rhizome of <i>Gastrodia elata</i> Blume (Tianma) is a functional food with medicinal value in China, used to improve the health of the central nervous system and reported to exhibit anti-cellular senescent activity. P-hydroxybenzaldehyde (P-HBA) is a key aromatic compound isolated from Tianma; however, its potential to mitigate cellular senescence remains unclear. <b>Methods</b>: We employed ultra-performance liquid chromatography-mass spectrometry to identify the chemical characterization of Tianma extract. Cell viability assay, senescence-associated-β-galactosidase (SA-β-Gal) assay, and immunofluorescence staining and autophagy analysis were used to evaluate the anti-senescent activity of P-HBA and other Tianma components. <b>Results</b>: Our findings demonstrate that Tianma methanol extract (TME) and P-HBA significantly reduce cellular senescent inducer hydroxyurea (HU)-induced DNA damage, SA-β-Gal activity increase, and autophagic dysfunction in human SH-SY5Y cells. Notably, an autophagy inhibitor, chloroquine, can reduce anti-cellular senescent activity of P-HBA. <b>Conclusions</b>: These results suggest that P-HBA exhibits the effect of reducing cellular senescent phenotypes, and its effect is achieved by enhancing autophagy.