Abstract:

This study aims to investigate the effect and mechanism of Huanglian Jiedu Decoction (HJD) on neuronal apoptosis and pyroptosis in rats with vascular dementia (VD). Ten rats were randomly selected from 70 rats as the sham group, while the remaining rats were subjected to modified bilateral common carotid artery occlusion to establish vascular dementia VD rat models,and the rats were randomly divided into model group, low-dose HJD group (1.5 g/kg), medium-dose HJD group (3.0 g/kg), high-dose HJD group (6.0 g/kg), high-dose HJD (6.0 g/kg) and JNK activator anisomycin group (5 mg/kg), with ten rats in each group. The water maze test was used to detect learning and memory, the pathological changes and apoptosis of hippocampus were observed, and the content of inflammatory factors in hippocampus was detected by ELISA. The expression of C-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), forkhead box protein O1(FOXO1), phosphorylated FOXO1 (p-FOXO1), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1), gasdermin D-N (GSDMD-N), Caspase-3, Caspase-9, B-cell lymphoma/leukemia-2 (BCL-2), BCL-2-associated-X-protein (BAX) was detected by Western blot and RT-qPCR. Compared with Mod group,the intervention of HJD improved the learning and spatial memory abilities of model rats significantly(P<0.05 or P<0.01), alleviated pathological morphology damage in hippocampal tissue, and reduced the number of neuronal apoptosis significantly(P<0.05 or P<0.01). The content of interleukin-1β (IL-1β), IL-18 and tumor necrosis factor-α (TNF-α) in hippocampus decreased significantly (P<0.05 or P<0.01), down-regulated the expression of JNK, FOXO1, NLRP3, ASC, Caspase-1, GSDMD-N, Caspase-3, Caspase-9, BAX proteins and mRNA (P<0.05 or P<0.01), and up-regulated the expression of BCL-2 protein and mRNA simultaneously (P<0.05 or P<0.01). However, the use of anisomycin partially reversed the therapeutic effect of HJD on apoptosis and pyroptosis. These results suggest that HJD effectively alleviated apoptosis and pyroptosis in VD rats by inhibited the JNK/FOXO1 signaling pathway, thereby improved the learning and memory ability of VD rats.

Key words: Huanglian Jiedu Decoction, vascular dementia, apoptosis, pyroptosis, JNK/FOXO1 signaling pathway