ObjectiveTo investigate the effect and mechanism of Guilu Erxiangao on
Alzheimer's disease (AD) model
rats induced by
hydrocortisone and
amyloid β-
protein(Aβ) based on the theory of
kidney-
brain correlation. MethodIntraperitoneal
injection of
hydrocortisone and intracerebroventricular
injection of Aβ were performed to induce AD in
rats, and different concentrations of Guilu Erxiangao were used for intervention. The indexes of
hippocampus,
kidney and
adrenal gland were measured, and the
spatial learning and
memory ability of AD
rats was observed by
Morris water maze experiment. The levels of
testosterone (T) and
corticosterone (CORT) in
serum samples were determined by
enzyme-linked immunosorbent assay (
ELISA).
Liquid chromatography-mass spectrometry (
LC-MS) was used to collect and analyze the
serum metabolic data of model
rats. The active components and corresponding targets of Guilu Erxiangao were collected using
Traditional Chinese Medicine Systems Pharmacology Database and
Analysis Platform(TCMSP), a
Bioinformatics Analysis Tool for Molecular mechANism of
Traditional Chinese Medicine (BATMAN-TCM) and
Traditional Chinese Medicine Integrated Database(TCMID). GeneCards and
Online Mendelian Inheritance in Man (
OMIM) were retrieved to obtain AD-related targets, and
protein-
protein interaction (PPI) network was constructed to perform
gene ontology (GO)and Kyoto
Encyclopedia of
Genes and
Genomes (KEGG) enrichment
analysis. The expression level of
interleukin-6 (
IL-6) in the
hippocampus of
rats was detected by
Western blot. ResultCompared with the model group, the low-, medium- and high-
dose groups of Guilu Erxiangao exhibited significantly increased
hippocampus index,
kidney index and
adrenal gland index, reduced CORT levels in
serum and down-regulated
IL-6 levels in hippocampal
tissues. According to the results of
water maze experiment, as compared with the model group, the platform crossing times of
rats was significantly increased in the low- and high-
dose groups of Guilu Erxiangao, with evidently prolonged distance traveled in quadrant Ⅲ (%) and
time in quadrant Ⅲ (%). A total of 24
serum differential metabolites associated with AD were identified by
LC-MS, and 50 high-frequency common compounds and 187 high-frequency common targets for AD
treatment were screened by
network pharmacology method. Results demonstrated
phosphatidylinositol 3-kinases(PI3K)/
protein kinase B(Akt) signaling pathway
plays an important
role in the complex AD pathological mechanism. ConclusionGuilu Erxiangao can significantly improve the
cognitive dysfunction of AD model
rats induced by
hydrocortisone and Aβ, reduce
serum CORT levels and
IL-6 levels in hippocampal
tissues, and regulate the metabolic level, which provides a reference for its clinical application.