Ginsenoside F1 suppresses astrocytic senescence-associated secretory phenotype. (1st March 2018)

• Record Type: Journal Article
• Authors: Hou, Jingang; Cui, Changhao; Kim, Sunchang; Sung, Changkeun; Choi, Chulhee
• Is Part Of: Chemico-biological interactions. Volume 283(2018)
• Page Start: 75
• Page End: 83
• Publication Date: 2018-03-01
• Subjects: Astrocytic senescent -- Ginsenoside F1 -- p38MAPK -- NF-κB -- SASP -- Glioblastoma; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.02.002
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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 byd -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. Highlights: F1 suppresses secretion IL-6 and IL-8, major components of senescence-associated secretory phenotype. F1 suppresses senescent secretory astrocytes via p38MAPK-dependent NF-κB activation. F1 suppresses senescent secretory astrocyte-induced proliferation and migration of brain tumor. F1 was safe to normal neuronal cells in brain.