Guyuan Jiannao decoction improves neurovascular unit dysfunction by regulating PI3K/AKT/NF-κB signaling pathway in...

Cerebral small vessel disease (CSVD) is a series of clinical, imaging, and pathological syndromes caused by brain microvascular damage and treated as a major contributing factor in many neurological diseases. Guyuan Jiannao Decoction (GYJND), a traditional Chinese formular, is clinically used for treating CSVD. However, the fundamental mechanism is nevertheless unknown.

To explore the potential mechanism underlying the effect of GYJND on CSVD.

UPLC-Q-TOF/MS was employed to identify the chemical components of GYJND. Subsequently, CSVD models were utilized to assess the impact of GYJND in vivo. Morris Water Maze (MWM) test was used to evaluate cognitive function. Hematoxylin-eosin (HE), luxol fast blue (LFB) staining and transmission electron microscope (TEM) were performed to observe pathological changes of brain. Morphology and function of endothelial cells, astrocytes, microglia, and neurons, including Occludin, GFAP and Iba-1 were detected using immunofluorescence (IF) and immunohistochemistry (ICH).

A total of 95 compounds were identified from GYJND, mainly including flavonoids, diterpenoids, triterpenoids, saponins, phenolic acids. In animal experiments, treatment with GYJND effectively improved cognitive function in rats, as observed by MWM. GYJND reduced brain tissue injury and improve the permeability of blood-brain-barrier (BBB) and microvascular structure. Further, the morphology and structural damage of neurovascular unit (NVU) were alleviated after treatment of GYJND. GYJND also attenuated neuronal apoptosis, increased NeuN, GFAP and decreased Iba-1, AQP4 level in the prefrontal cortex and hippocampus. In addition, GYJND upregulated PI3K/AKT expression and inhibited NF-κB expression.

Our study suggested that GYJND treatment can protect NVU in the prefrontal cortex and hippocampus of CSVD. These effects may be achieved by inhibiting NF-κB through activation of PI3K/AKT signaling.