As cellular senescence, reactive oxygen species (ROS) accumulate excessively, causing cellular damage. Flavonoids derived from natural products are known for their antioxidant effects and their ability to delay cellular senescence. Previous studies have attempted to mitigate cellular senescence using flavonoids from natural sources. However, the detailed mechanisms and regulatory targets of some flavonoids exhibiting antioxidant effects have not been fully elucidated. Therefore, we screened a library of flavonoids for antioxidant properties. Isoschaftoside, a glycosidic flavonoid, significantly reduced ROS levels in senescent cells. It was found that mitochondrial function was restored, and dependence on glycolysis was reduced in senescent cells treated with isoschaftoside. Additionally, we identified that isoschaftoside suppresses ROS by reducing the expression of RAC2 and LINC00294 in senescent cells. Taken together, this study establishes a novel mechanism for ROS inhibition and the regulation of cellular senescence by isoschaftoside. Our findings contribute important insights to antioxidant and anti-senescence research.

Neoshirakia japonica, a small deciduous tree belonging to the family Euphorbiaceae, has traditionally been used to relieve pain and fatigue in ancient Asia. To date, there have been no attempts to investigate the overall metabolite profiles of N. japonica. To obtain the phytochemical profiles of its aerial part and root, the extracts were analyzed by UHPLC Orbitrap mass spectrometry, and the metabolites were clustered using feature-based molecular networking (FBMN). The common major constituents of the two different parts were annotated as ellagitannins and ellagic acid derivatives using the GNPS database and SIRIUS software, and a total of 20 compounds were isolated. With FBMN guidance, five minor ginsenosides (10–14) were isolated from the BuOH fraction of the aerial part and first identified in this plant. Also, one new xanthoxylin derivative (16) was discovered from the root, and its antioxidant activity and binding potential to NOX family proteins were evaluated by in silico studies. Consequently, this research aims to provide a comprehensive understanding of the major and minor components of N. japonica by part and suggests its potential as a drug candidate for antioxidant-related diseases.