Tea Polyphenols Protect the Blood–Brain Barrier Structure in the Hippocampus of Early Diabetic Mice by Inhibiting the AGEs–RAGE Pathway

Background: Diabetic encephalopathy is a prevalent complication of diabetes mellitus, which is primarily characterized by hippocampal injury and blood-brain barrier (BBB) dysfunction. This study investigates the neuroprotective effect of tea polyphenols (TP) on hippocampal tissue in early-stage diabetic mice. Methods: Sixty BALB/c mice were randomly assigned to the control group (C), the diabetes group (T0), and the TP-treated group (T1). After successful model induction, mice in group T1 received TP intragastrically (100 mg/kg/d). Hematoxylin and eosin (H&E), toluidine blue, and Hoechst 33342 staining, combined with polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), were used to assess the effects of TP on hippocampal histology, inflammation and oxidative stress, the advanced glycation end products (AGEs) – Receptor for Advanced Glycation End products (RAGE) pathway, and the expression of key proteins associated with the BBB. Results: The contents of AGEs, RAGE, NF-κB, P-glycoprotein (P38), and oxidative stress factors in group T1 were lower than those in group T0 at 7, 14, and 21 days (p < 0.05). At the same time points, the mRNA expression levels of inflammatory factors in group T1 were lower than those in group T0 (p < 0.05). Moreover, compared with group T0, both P-glycoprotein (P-gp) protein expression and glucose transporters (Glut1) mRNA expression increased in group T1 (p < 0.05). The mRNA expression levels of key BBB-related molecules in group T1 also increased to varying degrees (p < 0.05). Histopathological analysis showed marked improvement in the hippocampal architecture of group T1 compared with group T0. Moreover, the expression levels of P38, NF-κB, IL-6, TNF-α, ROS, and Glut1 were significantly or highly significantly positively correlated with RAGE protein levels (p < 0.05 or p < 0.01). Conclusions: TP enhanced BBB structural integrity by inhibiting the AGEs–RAGE pathway, thereby attenuating hippocampal tissue damage.