OBJECTIVE  To investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction (HGWD) on cerebral ischemia injury, and to explore the underlying mechanism.

  METHODS  Fifty rats were randomly divided into 5 groups: sham operation group (sham), middle cerebral artery occlusion (MCAO) model group, and MCAO rats treated with HGWD at 5, 10, 20 g·kg^-1. The first two groups were administered intragastrically (i.g.) with saline for 7 days, while HGWD groups were treated with HGWD at 5, 10, and 20 g·kg^-1, correspondingly. The neurological deficits scores, cerebral infarct size, lipid peroxidation and inflammatory cytokines levels were used to evaluate the brain ischemic injury. The possible mechanism of HGWD on cerebral ischemia-perfusion injury was investigated by metabolomics.

  RESULTS  HGWD treatment significantly attenuated middle cerebral artery occlusion (MCAO)-induced brain ischemic injury of rats as evidenced by decreasing the neurological deficits scores, cerebral infarct size, as well as lipid peroxidation and inflammatory cytokines levels. Further metabolomics study indicated that great metabolic disorders in serum were induced following cerebral ischemia/reperfusion injury. Totally 23 metabolites associated with ischemic stroke were proposed as potential biomarkers. The metabolic pathway analysis revealed that MCAO induced brain ischemic injuries mainly by targeting glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. Correspondingly, HGWD could restore most of the imbalanced endogenous metabolites.

  CONCLUSION  HGWD plays a protective role in focal cerebral ischemia-reperfusion injury in rats, which may be associated with the inhibition of inflammatory effect and improvement of multiple metabolic pathways.