Senescence is one of the hallmarks of aging and identified as a potential therapeutic target in the treatment of aging and aging-related diseases. Senescent cells accumulate with age in a variety of human tissues where they develop a complex senescence-associated secretory phenotype (SASP). SASP in brain could contribute to age-related inflammation and chronic neurodegenerative diseases. We confirmed that senescent astrocytes express a characteristic of SASP in vitro by human cytokine antibody array. Ginsenoside F1 suppresses the SASP from astrocytes induced by D-galactose via suppressing p38MAPK-dependent NF-κB activity. A specific inhibitor of p38MAPK, SB203580 significantly decreased the secretion of IL-6 and IL-8, the major components of SASPs. Additionally, treatment of senescent astrocytes with NF-κB inhibitor, BAY 11–7092, also suppressed the secretion of IL-6 and IL-8, suggesting NF-κB was required for SASP. Importantly, conditioned media from senescent astrocytes promoted the migration of glioblastoma cells, such as U373-MG, U251-MG and U87-MG assessed by scratch wound healing. This migration was significantly decreased by F1 treatment in senescent astrocytes. Interestingly, IL-8, the main mediator regulating glioblastoma cell invasion, was suppressed in both transcriptional and protein level. Herein, we propose ginsenoside F1 as a potential therapeutic strategy for reducing the deleterious contribution of senescent astrocytes in aged brain and related diseases.

衰老是衰老的标志之一，被确定为衰老和衰老相关疾病的潜在治疗靶标。随着年龄的增长，衰老细胞会在各种人体组织中积累，并在这些组织中发展出复杂的衰老相关分泌表型（SASP）。大脑中的SASP可能导致与年龄有关的炎症和慢性神经退行性疾病。我们确认衰老的星形胶质细胞在体外表达SASP的特征通过人细胞因子抗体阵列。人参皂苷F1通过抑制p38MAPK依赖性的NF-κB活性来抑制D-半乳糖诱导的星形胶质细胞中的SASP。p38MAPK的特异性抑制剂SB203580可显着降低SASP的主要成分IL-6和IL-8的分泌。此外，用NF-κB抑制剂BAY 11–7092处理衰老的星形胶质细胞，也抑制了IL-6和IL-8的分泌，这表明SASP需要NF-κB。重要的是，来自衰老的星形胶质细胞的条件培养基促进了胶质母细胞瘤细胞的迁移，例如通过刮擦伤口愈合评估的U373-MG，U251-MG和U87-MG。F1处理在衰老的星形胶质细胞中显着降低了这种迁移。有趣的是，IL-8是调节胶质母细胞瘤细胞侵袭的主要介质，在转录和蛋白质水平上均受到抑制。在此处，