Emodin Suppresses Fluoride-Induced Pyroptosis in SH-SY5Y Cells Through the Inhibition of NLRP3 Inflammasome Activation

Abstract

Our preliminary investigation has unveiled that emodin may inhibit the neurotoxic effects of sodium fluoride (NaF) on SH-SY5Y cells by deactivating ERK and activating the Nrf2/HO-1 signaling pathway. This action thereby restores synaptic damage and reduces excessive reactive oxygen species (ROS) generation. To delve further into the neuroprotective effects of emodin on neuronal cells, our study revealed that 48 h of NaF treatment disrupted the balance between mitochondrial fission and fusion in SH-SY5Y cells. This disruption significantly upregulated proteins associated with pyroptosis pathways, including NLRP3, Caspase-1, IL-1β, and GSDMD expression, while inhibiting NF-κB phosphorylation. Notably, pretreatment with emodin effectively reinstated these alterations induced by NaF exposure, indicating its capacity to not only mitigate ROS production but also regulate mitochondrial dynamics and pyroptosis pathways. This counteraction of the toxic effects of NaF on SH-SY5Y cells provides valuable insights into the neuroprotective role of emodin.