Shenzhi Jiannao formula ameliorates vascular dementia in vivo and in vitro by inhibition glutamate neurotoxicity via promoting clathrin-mediated endocytosis

Abstract Background Synaptic damage and glutamate excitotoxicity have been implicated in the pathogenesis of vascular dementia (VD). Clathrin, RAB5B N -methyl- d -aspartic acid receptor 1 (NMDAR1) proteins play a vital role endocytosis synaptic vesicles neurons over accumulation. Previous researches confirmed that Shenzhi Jiannao (SZJN) formula has an anti-apoptotic neuroprotective effect VD, but underlying mechanisms are still unclear. In this study, we aimed to explore SZJN on cognitive impairment via clathrin-mediated (CME) vivo vitro. Methods consists Panax ginseng C.A.Mey., Anemarrhena asphodeloides Bunge, Paeonia anomala subsp. veitchii (Lynch) D.Y.Hong & K.Y.Pan. All herbs were prepared into granules. Both common carotid arteries permanent occluded (2?vessel occlusion, 2VO) male Sprague Dawley (SD) rats model VD. One day after operation, began daily treatment with for 2 weeks. The effects was subsequently assessed by novel object recognition test, Morris water maze, hematoxylin–eosin (HE) staining Nissl staining. Glutamate cytotoxicity detecting cell viability death PC12 cells. Immunohistochemistry, immunofluorescence, Western blot, quantitative real?time PCR used detect expression levels clathrin, RAB5B, NMDAR1. Results Administration effectively improved short-term memory spatial memory. significantly reduced hippocampal neuronal loss, recovered arrangement morphology bodies. Moreover, promoted proliferation cells inhibited glutamate-induced death. down-regulation clathrin as well upregulation NMDAR1 brain induced 2VO or also notably reversed at both protein mRNA levels, which may contribute neurological function. Conclusions Taken together, our findings provide evidence experimental VD maybe mediated through promoting reducing NMDARs?associated excitotoxicity. serves promising alternative therapy be useful herbal medicine preventing progression Graphic abstract