Glycine tabacina (Labill.) Benth. Ethanol Extract Attenuates LPS-Induced Neuroinflammation and Behavioral Deficits by Modulating TLR4/NF-κB/NLRP3 Signaling Pathway

Glycine tabacina (Labill.) Benth is commonly known as “Yan-Dou” and is a folk medicinal herb in China used to alleviate rheumatism. Although its anti-inflammatory and antioxidant activities have been reported, its effects on microglia-driven neuroinflammation, neuronal protection, and neuroinflammation-associated behavioral impairment have not been investigated. An LPS-stimulated microglial activation model was established using BV2 cells to evaluate the anti-neuroinflammation activity of Glycine tabacina extract (GTE) and to explore its underlying mechanisms. Neuroprotective efficacy was assessed using a BV2–HT22 conditioned interaction model to determine whether GTE mitigates microglia-mediated neuronal injury. A zebrafish model was used to examine the effects of GTE on LPS-induced neuroinflammatory phenotypes and behavioral deficits. GTE significantly inhibited LPS-induced neuroinflammation in BV2 microglia. GTE also showed a strong neuroprotective effect by suppressing HT22 cell death in the BV2-HT22 conditioned interaction model. Mechanistic assays indicated that the neuroprotective effects of GTE were associated with the inhibition of TLR4/NF-κB/NLRP3 signaling cascade. In vivo studies showed that GTE mitigated LPS-stimulated neuroinflammatory phenotypes in both peripheral and central compartments and significantly improved behavioral performance in zebrafish. The results of this study demonstrate remarkable neuroprotective and anti-neuroinflammatory effects of GTE through regulation of the TLR4/NF-κB/NLRP3 signaling pathway and highlight its potential as a therapeutic candidate for neuroinflammation-related CNS disorders.