Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach

Radix Polygoni Multiflori (PM) is a well−known nootropic used in traditional Chinese medicine (TCM). Considering the efficacy and application discrepancy between raw (RPM) and processed PM (PPM), the similarities and differences between them in the treatment of vascular dementia (VaD) is intriguing. In this study, a VaD rat model was constructed by 2−vessel occlusion (2−VO). During 28 days of treatment, plasma was collected on days 7, 14, 21, and 28 after the start of dosing and the metabolic profile was analyzed by HPLC−MS/MS−based metabolomics. The Morris Water Maze Test, hematoxylin–eosin and Nissl staining, and biochemical analysis were used to assess cognitive function, pathogenic alterations and oxidative stress, respectively. RPM and PPM effectivelyreducedthe 2VO−induced cognitive impairment and mitigated histological alterations in hippocampus tissue. The 2−VO model significantly elevated MDA level and decreased SOD activity and GSH level, indicating severe oxidative stress, which could also be attenuated by RPM and PPM treatment. RPM outperformed PPM in decreasing MDA levels while PPM outperformed RPM in increasing GSH levels. Differential metabolites were subjected to Metabolite Set Enrichment Analysis (MSEA) and genes corresponding to proteins having interactions with metabolites were further annotated with Gene Ontology (GO). Both RPM and PPM ameliorated VaD−relevant vitamin B6 metabolism, pentose phosphate pathways, and taurine and hypotaurine metabolism. In addition, the metabolism of cysteine and methionine was regulated only by RPM, and riboflavin metabolism was modulated only by PPM. The results suggested that raw and processed PM had comparable efficacy in the treatment of VaD but also with some mechanistic differenece.