Comparative Phytochemical Profiling and Phenotypic Senolytic Screening of Botanical Extracts for Oxidative-Stress-Induced Skin-Cell Senescence

Cellular senescence contributes to skin aging through the accumulation of senescent cells and the secretion of senescence-associated secretory phenotype (SASP) factors. Although numerous botanical flavonoids have been reported to possess antioxidant and anti-aging properties, the relationship between phytochemical composition, antioxidant capacity, and senolytic activity in complex botanical extracts remains poorly understood. In this study, twenty botanical extracts were systematically compared using a standardized screening platform that integrated total flavonoid quantification, UPLC-Q-TOF-MS phytochemical profiling, antioxidant evaluation, cytotoxicity assessment, and phenotypic senolytic screening in oxidative-stress-induced human foreskin fibroblast (HFF) senescence models. Among the tested extracts, chlorella, water lily, green tea, and rosemary exhibited the most pronounced senolytic-associated activities while maintaining minimal cytotoxicity toward non-senescent fibroblasts. UPLC-Q-TOF-MS analysis revealed that these extracts possessed distinct flavonoid-enriched phytochemical fingerprints despite producing comparable biological responses. Notably, green tea extract exhibited the strongest antioxidant activity, whereas its phytochemical composition differed substantially from those of the other highly active extracts, indicating that antioxidant capacity alone does not predict senolytic efficacy. Collectively, the findings demonstrate that total flavonoid content, antioxidant activity, and senolytic activity are not necessarily directly correlated and highlight the importance of comprehensive phytochemical characterization combined with phenotypic biological screening for identifying botanical resources with senescence-modulating potential. These results provide a practical comparative strategy for discovering multifunctional botanical ingredients applicable to oxidative-stress-associated skin aging.