Fo-Shou-San improves cognitive function in rats with vascular dementia (VaD) by inhibiting neuroinflammation and pyroptosis
We utilized the bilateral common carotid artery ligation (BCCAL) method to establish a VaD rat model and evaluated the therapeutic effects of FSS. Cognitive improvement in VaD rats following FSS treatment was assessed through behavioral experiments. Neuronal damage in the hippocampal region was observed using Nissl staining and hematoxylin-eosin (HE) staining. The expression of inflammatory cytokine genes and microglial cell activation in the rat hippocampal region was evaluated using RT-qPCR and quantitative immunohistochemistry. TUNEL staining, RT-qPCR, and Western blot techniques were employed to assess pyroptosis in the rat hippocampal tissue. Subsequently, based on high-performance liquid chromatography (HPLC) analysis, FSS derivatives were screened through molecular docking to identify the optimal compound that binds to the key pyroptosis target Caspase-1. Finally, in vitro validation demonstrated that FSS derivatives could inhibit the inflammatory response and pyroptosis induced by lipopolysaccharide (LPS) + adenosine triphosphate (ATP), in accordance with the results of molecular docking analysis.