Nan Fang Yi Ke Da Xue Xue Bao. 2026 Jan 20;46(1):191-199. doi: 10.12122/j.issn.1673-4254.2026.01.21.
ABSTRACT
OBJECTIVES: 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 Aβ42 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.
CONCLUSIONS: SFN attenuates astrocyte-mediated neuron apoptosis by inhibiting the MAPK/NF-κB signaling pathway in Aβ42 oligomer-activated astrocytes.
PMID:41540706 | PMC:PMC12809040 | DOI:10.12122/j.issn.1673-4254.2026.01.21