Kanzan cherry blossom and its active compounds attenuate methylglyoxal-induced skin fibroblast senescence through RAGE/NF-κB suppression and ECM restoration

Introduction The accumulation of advanced glycation end products (AGEs) is a key driver of skin aging, accelerating the process through oxidative stress, inflammation, and disruption of extracellular matrix (ECM) homeostasis. Cerasus serrulata 'Sekiyama' Kanzan cherry blossom (KCB) is rich in bioactive compounds with antioxidant and anti-glycation potential. However, its compositional variations across flowering stages and their functional relevance remain unclear. Methods This study systematically characterized the chemical profile of KCB using UPLC-QTOF-MS and monitored six major active components across four flowering stages using UPLC-MS/MS. The anti-glycation, antioxidant, tyrosinase, and collagenase activities of the identified compounds were evaluated in vitro . The protective effects of KCB extract (KCBE) and major active compounds were further investigated in a methylglyoxal (MGO)-induced human skin fibroblast senescence model. Results Thirteen compounds were identified, including one organic acid, five flavonoid glycosides, and seven phenolic acids. The half-bloom stage (KCB3) contained the highest levels of the six quantified compounds. 1- O -caffeoyl glucoside (CG) was the predominant phenolic acid (8.025 ± 0.203%), while quercetin 3- O -6 ′′ - O -malonyl-β-glucopyranoside (QMG) was the major flavonoid (1.155 ± 0.035%). QMG showed strong anti-glycation activity (IC50 = 0.41 ± 0.01 mM), whereas CG exhibited strong tyrosinase (IC 50 = 0.19 ± 0.03 mM) and collagenase inhibition (IC 50 = 2.51 ± 0.90 mM). KCBE, QMG, and CG significantly alleviated MGO-induced cellular senescence, reduced intracellular ROS, restored F-actin organization, and promoted type I collagen deposition. These effects were associated with suppression of RAGE/NF-κB signaling, normalization of the Nrf2/HO-1-mediated antioxidant response, and restoration of ECM-related gene expression. Discussion Half-bloom KCB exhibits prominent anti-glycation and anti-skin-aging activities, with CG and QMG representing major bioactive constituents. These findings indicate that KCB and its characteristic phenolic acid and flavonoid constituents may have potential as natural functional ingredients for skin health.