Stigmasterol ameliorates neurological deficits and neuroinflammation in rats with traumatic brain injury by suppressing STAT3/NF-κB/LCN-2.

purposeTBI triggers intricate inflammatory processes that lead to secondary damage. Stig, a compound known for its cholesterol-lowering effects, demonstrates significant therapeutic potential, encompassing anti-cancer, antioxidant, and anti-atherosclerotic properties. It possesses an ability to penetrate the blood-brain barrier and accumulate in the brain, where it exerts potent anti-inflammatory, anti-apoptotic, and anti-oxidative stress properties, specifically in conditions impacting the central nervous system.

methodsThis study is a basic research combining in vitro and in vivo experiments. The experimental subjects include BV2 microglia (a murine-derived microglial cell line) and HT22 neurons (a murine-derived hippocampal neuronal cell line). A total of 60 Sprague-Dawley rats (aged 8 weeks, weighing 200-250 g) were used, with 3 samples of Sprague-Dawley rats in each group. In vitro experiments involved stimulating BV2 mouse microglial cells with LPS and HT22 mouse neuronal cells with H

resultsIn vivo treatment with Stig ameliorated neurological dysfunction, brain edema, and neuronal apoptosis in TBI rats while enhancing both memory and learning performance. Stig reduced microglial activation and inflammatory responses in TBI by inhibiting the STAT3/NF-κB pathway and downregulating LCN-2 expression. Additionally, Stig markedly attenuated inflammation in LPS-stimulated microglial cells and reduced neuronal apoptosis and oxidative stress in H₂O₂-treated HT22 cells. Moreover, it effectively suppressed the activation of the STAT3/NF-κB/LCN-2 signaling cascade induced by LPS or H₂O₂.

conclusionStig mitigates neuroinflammation and neuronal cell death by suppressing the STAT3/NF-κB/LCN-2 signaling cascade, offering neuroprotective effects in a rat TBI model.