<i>Lycium Barbarum</i> Polysaccharides Alleviate Hyperglycemia‐Aggravated Cerebral Ischemia/Reperfusion Injury by Up‐Regulating Wnt/β‐Catenin Signaling

Abstract Hyperglycemia aggravates neuronal damage in cerebral ischemia/reperfusion (I/R) injury. Emerging evidence indicates that Lycium barbarum polysaccharides (LBP) possess significant neuroprotective properties. However, the underlying mechanism by which LBP alleviates hyperglycemia‐aggravated cerebral I/R injury remains unclear. This study aims to investigate the effects of LBP on hyperglycemia‐aggravated cerebral I/R injury using in vivo and in vitro models. Rats are randomly assigned to the following groups: normoglycemic (NG), hyperglycemic (HG), and LBP‐pretreated hyperglycemic (LBP) groups. Streptozotocin‑induced hyperglycemic rats undergo middle cerebral artery occlusion (MCAO) for 30 min, followed by reperfusion for 1, 3, and 7 days. Meanwhile, an in vitro model of hyperglycemia‐aggravated cerebral I/R injury is established using murine hippocampal neuronal HT22 cells subjected to high glucose (HG) conditions combined with oxygen deprivation and reoxygenation (OD). The results demonstrate that compared to the NG group, the HG group exhibits significantly increased neurological deficit and larger infarct area. Pre‐treatment with LBP significantly attenuates these hyperglycemia‐aggravated neurological deficits and reduces the infarct area. Furthermore, LBP treatment elevates the cell viability of HT22 cells in the HG and OD groups. Additionally, LBP significantly alleviates the hyperglycemia‐induced downregulation of β‐catenin and p‐GSK‐3β expression both in vivo and in vitro. These results demonstrate that LBP alleviates hyperglycemia‐aggravated cerebral I/R injury by upregulating the Wnt/β‐catenin signaling pathway.