Mol Nutr Food Res. 2026 Jun;70(11):e70510. doi: 10.1002/mnfr.70510.
ABSTRACT
This study aimed to elucidate the role of the TLR4 pathway in the antiepileptic effects of sulforaphane (SFN). C57BL/6 mice were randomized into control, SFN, epilepsy (EP), and SFN intervention groups. SFN was administered for 7 days (25 mg/kg/day, oral gavage) to the intervention and SFN groups before epilepsy was induced. Epilepsy was induced in the EP and intervention groups using a lithium chloride-pilocarpine protocol. Behavioral and electroencephalogram (EEG) data were collected. Hippocampal tissue was examined for inflammatory markers and histopathological changes, and protein expression in the TLR4/NFโฮบB/NLRP3 pathway was assessed by western blot. The involvement of TLR4 was further validated through intraperitoneal administration of the selective inhibitor TAKโ242 (3.0 mg/kg). SFN pretreatment significantly ameliorated seizure severity, mortality, pathologically elevated EEG delta wave frequency, hippocampal proโinflammatory cytokine levels, and neuronal damage (p < 0.05). Molecular analysis showed that SFN reduced the expression of TLR4, MyD88, p-NF-ฮบB, NLRP3, and caspase-1 (p < 0.05). SFN combined with TAK-242 did not further enhance the reduction of these indicators, compared with SFN alone. The TLR4/NF-ฮบB/NLRP3 signaling pathway plays a crucial role in SFN-mediated attenuation of neuroinflammation and contributes to its antiepileptic and neuroprotective effects.
PMID:42220202 | DOI:10.1002/mnfr.70510