[Nordicon Capsules improves cognitive and motor functions in rats with cerebral small vessel disease by promoting...

This study aimed to investigate the therapeutic effects of Nordicon Capsules(NDC) in a rat model of cerebral small vessel disease(CSVD) and to elucidate the molecular mechanisms of NDC in improving cognitive and motor functions in CSVD model rats through activation of the PI3K/Akt signaling pathway and promotion of angiogenesis. A CSVD rat model was established using permanent bilateral common carotid artery ligation(2-VO). Butylphthalide Soft Capsules were used as a positive control, and NDC(300, 600, and 900 mg·kg~(-1)·d~(-1)) were administered intragastrically for 28 consecutive days. Cognitive function in CSVD model rats was evaluated using the Morris water maze and shuttle box tests, while motor coordination was assessed by gait analysis and the open field test. The results showed that NDC significantly improved cognitive and motor functions in CSVD model rats. Cerebral blood flow measurements indicated that NDC significantly promoted blood flow recovery. HE staining, Nissl staining, and Neun immunohistochemistry further confirmed that NDC effectively alleviated neuronal disorganization, neuronal loss, and cellular pyknosis and necrosis in the hippocampal CA1 region, demonstrating clear neuroprotective effects. Immunofluorescence co-staining revealed that NDC significantly increased the number of cells co-expressing CD31+Ki67, a marker of proliferating brain microvascular endothelial cells, indicating that NDC promoted functional angiogenesis. Western blot showed that NDC significantly upregulated the protein expression levels of VEGFA and its receptor VEGFR2 in brain tissue and activated the downstream PI3K/Akt signaling pathway. In summary, NDC may activate the PI3K/Akt signaling pathway via VEGFA/VEGFR2, thereby driving angiogenesis and improving cognitive and motor functions in CSVD model rats, providing a theoretical basis for the clinical application of NDC in the treatment of CSVD.