Sulforaphane reduces reactive astrocyte-mediated neuron apoptosis in vitro by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes
ZHANG Shufen
HUANG Tianrong
YANG Canhong
CHEN Jiayi
LÜ Tianming
ZHANG Jiafa
Abstract：Objective To explore the effects of sulforaphane(SFN)on Aβ42-activated U87 astrocyte-mediated apoptosis of SH-SY5Y neurons in vitro.Methods U87 cells treated with different concentrations of Aβ42,SFN or both were examined for changes in cell activity,IL-6 and TNF-α mRNA expression,release of IL-6 and TNF-α proteins,and expressions of p-p38,p-p65 and GFAP using CCK-8 assay,RT-qPCR,ELISA and Western blotting.SH-SY5Y neurons were co-cultured with U87 astrocytes treated with Aβ42 alone or in combination with SFN or SB203580 for 24 h,and the changes in Bax protein expression levels and viability of SH-SY5Y cells were examined.The effects of Aβ42,SFN,and their combination were also observed in astrocytes isolated from mouse brain tissues,and the indirect effects of astrocyte treatmentt on viability of the co-cultured primary neurons were assessed.Results The viability of U87 astrocytes increased significantly following treatment with 1.25 μmol/L Aβ 42 but decreased after Aβ42 treatment above 5 μmol/L.SFN treatments for 24 h below 5 μmol/L did not significantly affect U87 cell viability.Aβ42 treatment significantly increased protein expressions of p-p38,p-p65 and GFAP,mRNA expression levels of IL-6 and TNF-α,and IL-6 and TNF-α levels in culture supernatant of U87 cells.SH-SY5Y cells co-cultured with Aβ42-treated U87 cells showed significantly increased protein expressions of Bax,and exhibited lowered viability following co-culture with 5 μmol/L Aβ42-treated U87 cells.The isolated mouse astrocytes showed lowered viability following Aβ42 treatment above 10 μmol/L,but SFN treatment below 5 μmol/L for 24 did not obviously affect the cell viability.The primary neurons co-cultured with Aβ42-treated mouse astrocytes showed significantly lower cell viability than those co-cultured with the astrocytes treated with Aβ+SFN or Aβ+SB203580.Conclusion SFN attenuates astrocyte-mediated neuron apoptosis by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes.
Keywords：sulforaphaneAlzheimer's diseaseastrocyteβ-amyloidMAPKnuclear factor-κBneuroinflammationapoptosis
Publication Date：2026-01-20
Online Publishing Date：2026-01-22(First online date of this platform, not the publication date of the document)
Pages：9( 191-199 )