Asparagus Saponin Officinalisnin-II Alleviates Fluoride-Induced Neurotoxicity Via Activation of the SIRT1/BDNF Signaling Pathway.

Excessive fluoride exposure induces oxidative stress, inflammation, and neuronal damage, leading to cognitive dysfunction. This study investigated the neuroprotective mechanism of asparagus saponin Officinalisnin-II against fluoride-induced brain injury through modulation of the Silent Information Regulator 1 (SIRT1) / Brain Derived Neurotrophic Factor (BDNF) signaling pathway. Cytotoxicity and protective effects were evaluated in BV2 microglial cells treated with sodium fluoride (NaF) and various concentrations of Officinalisnin-II using cell viability, crystal violet, and EdU assays. Flow cytometry and Western blotting were employed to assess cell cycle, apoptosis, oxidative stress, and inflammatory markers. Expression of SIRT1/BDNF-related proteins was analyzed by Western blotting and immunofluorescence. The neurobehavioral effects were further examined in zebrafish using a T-maze test and quantitative real-time PCR (qRT-PCR). Officinalisnin-II markedly restored the proliferative activity of NaF-exposed BV2 cells, reduced apoptosis, and normalized cell-cycle progression. It significantly decreased intracellular reactive oxygen species and malondialdehyde levels, enhanced superoxide dismutase, glutathione peroxidase, and total antioxidant capacity, and suppressed interleukin-1 and interleukin-6 expression. The treatment upregulated SIRT1, BDNF, tropomyosin receptor kinase B (TrkB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), while downregulating forkhead box protein O1A (FOXO1A), indicating activation of the SIRT1/BDNF pathway. In zebrafish, Officinalisnin-II improved learning and memory performance and increased expression of neuroprotective genes. These findings demonstrate that asparagus saponin Officinalisnin-II effectively mitigates fluoride-induced neurotoxicity by enhancing antioxidant capacity, reducing inflammation, and activating the SIRT1/BDNF signaling cascade, providing experimental evidence for its potential use in preventing fluorosis-related brain injury.