Polygonati Rhizoma Alleviates Vascular Dementia through Regulating Microglial Polarization Transitions Mediated by NF-κB/NLRP3 Pathway

OBJECTIVES: Polygonati rhizoma (PR) has been used for thousands of years to alleviate dementia. Here, we aimed to elucidate the effect of alleviating vascular dementia (VaD) and underlying mechanism of PR. METHODS: In vivo, rats were treated with two-vessel occlusion (2VO) induces VaD. The anti-VaD effect measured by learning and memory capacity, cerebral pathological structure, and cerebral microglial M1/M2 phenotype biomarkers. Subsequently, screening potential mechanisms of PR for VaD using network pharmacology and molecular docking methods. Moreover, the efficacy of PR-contained serum on LPS-induced inflammation and polarization on BV2 microglia was evaluated with NF-κB/NLRP3 pathway. RESULTS: In vivo, PR significantly enhanced learning and memory capacity, suppressed M1 microglia activation and promoted M2 polarization. Through network pharmacology and molecular docking approaches, we screened inflammation as a potential mechanism for PR anti-VaD, with targets involving NF-κB. Meanwhile, PR could regulate the expression of NF-κB/NLRP3 pathway compared with that of LPS-induced BV2 cells. Furthermore, by utilizing PDTC, an NF-κB antagonist, it was found that the effect of PR was similar to that of PDTC. CONCLUSION: PR could hamper inflammation and microglial polarization in 2VO-induced VaD and LPS-induced BV2 cells. Our results showed that PR was a promising Chinese herb to alleviate VaD, and the potential mechanism might be related to NF-κB/NLRP3 signaling pathway.