SIRT3 enhances the protective effect of Xyloketal B on seizure-induced brain injury by regulating AMPK/mTOR signaling-mediated autophagy.

Brain damage in children due to seizures is irreversible and has been a major public health concern. The herbal monomer Xyloketal B (Xyl-B) can be used as a neuroprotective drug because of its antioxidant, antiapoptotic, and anti-inflammatory effects but with few adverse effects. In this article, we constructed a rat developmental convulsion model and a primary hippocampal neuronal cell convulsion model, through which we studied hippocampal neuronal morphology and neuronal apoptosis using H&E staining and TUNEL staining, respectively. Moreover, we measured TNF-α, IL-6, and IL-1β inflammatory factor levels using ELISA, MDA, and SOD kits. The expression of SIRT3 in hippocampal tissues was determined by qPCR and Western blotting. The expression of autophagy-related proteins such as LC3, p62, and Beclin-1 was evaluated by Western blotting or immunohistochemistry. The role of SIRT3 and autophagic activity with Xyl-B in convulsive seizure-induced brain injury was investigated by knocking down SIRT3 expression levels. Our results showed that Xyl-B plays a neuroprotective role in convulsive seizure-induced brain injury by increasing SIRT3 expression and activating the autophagy pathway. The regulatory role of SIRT3 in the autophagy pathway with Xyl-B treatment was explored by knocking down SIRT3 expression and inhibiting autophagy. Our results revealed that SIRT3 enhances the protective effect of Xyl-B against postconvulsive brain injury by regulating AMPK/mTOR signaling-mediated autophagy.