Strychnos potatorum seed water ameliorates fluoride-induced oxidative stress and synaptic dysfunction in SK-N-SH cells by regulating the BDNF-TrkB signaling pathway

Objective Fluoride-induced oxidative stress and synaptic dysfunction pose significant threats to neural health. This research investigated the potential ameliorative effects of Strychnos potatorum seed (SPS)-treated water on fluoride-induced neurotoxicity using SK-N-SH cells as an in vitro model system. Methods To elucidate the underlying molecular mechanisms involved, we focused on the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway, a crucial modulator of synaptic plasticity, and neuroprotection. Results Our study revealed that Strychnos potatorum seed water administered for 48 to 96 h improved cell viability, as evidenced by enhanced cell survival rates and preserved cellular architecture, and that SPS-treated water effectively attenuated fluoride-induced oxidative stress, as evidenced by a reduction in reactive oxygen species (ROS). Furthermore, SPS-treated water significantly improved synaptic function, as indicated by enhanced expression of synaptic proteins, including synaptophysin (SYN 1) and postsynaptic density 95 (PSD-95). SPS water upregulated BDNF expression and promoted the activation of its cognate receptor, TrkB, in fluoride-challenged SK-N-SH cells. In addition, SPS-treated water-mediated regulation of the mitogen-activated protein kinase (MAPK) signaling cascade was observed, with increased phosphorylation of extracellular signal-regulated kinase (ERK). Conclusion These results suggest that SPS-treated water exerts neuroprotective effects against fluoride-induced neurotoxicity by targeting the MAPK-mediated BDNF-TrkB signaling pathway. However, further research is needed to investigate the effectiveness of SPS in vivo and its potential use as a neuroprotective agent.