Investigating the protective mechanism of Astragalus membranaceous (Fisch.) against cerebral ischemia-reperfusion injury in rats: A metabolomics and network pharmacology approach

Astragalus membranaceous (Fisch.) has a rich history as a traditional medicine in various Asian countries, showcasing a notable neuroprotective effect. However, the underlying therapeutic mechanisms warrant further investigation. This study employs metabolomics and network pharmacological analysis to elucidate the protective effects of Radix Astragali (Huangqi, HQ) against cerebral ischemia-reperfusion injury (CI/RI) in rats. The investigation aims to reveal the potential protective mechanisms of HQ in CI/RI rats. Plasma metabolomics analysis, utilizing multivariate statistical methods, highlights biomarkers and associated metabolic pathways. The integrated approach of network pharmacology comprehensively analyzes HQ’s effective components, therapeutic targets, and amino acid metabolites. Pharmacodynamic experiments demonstrate a significant cerebral protective effect in the HQ group compared to the model group (p < 0.05). Metabolomics results indicate significant differences (P < 0.05) in L-glutamic acid, L-arginine, L-ornithine hydrochloride, L-valine, and L-phenylalanine in the model group compared to the sham operation group, indicating plasma metabolic disorders in CI/RI rats. Network pharmacology analysis identifies quercetin, kaempferol, and astragaloside IV components within HQ that may act on IL6, TNF, and IL-1B targets, influencing five different amino acids to exert brain protection. This study provides valuable insights into the neuroprotective mechanisms of HQ in the context of CI/RI.