Title:The Molecular Mechanism of Scutellaria baicalensis Georgi Stems and
Leaves Flavonoids in Promoting Neurogenesis and Improving Memory
Impairment by the PI3K-AKT-CREB Signaling Pathway in Rats
Volume: 25
Issue: 5
Author(s): Qian-Qian Liu, Sheng-Kai Ding, Hui Zhang and Ya-Zhen Shang*
Affiliation:
- Institute of Traditional Chinese Medicine, Chengde Medical College, Hebei Province Key Research Office of
Traditional Chinese Medicine Against Dementia, Hebei Province Key Laboratory of Traditional Chinese Medicine
Research and Development Hebei Key Laboratory of Nerve Injury and Repair, Chengde, Hebei 067000, China
- The
Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, China
Keywords:
Scutellaria baicalensis Georgi stems and leaves flavonoids, Alzheimer's disease, neurogenesis, PI3K-AKT-CREB signaling pathway, memory impairment, molecular mechanism.
Abstract:
Aim: The aim of this study was to investigate the effect and molecular mechanism
of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in promoting
neurogenesis and improving memory impairment induced by the PI3K-AKT-CREB signaling
pathway.
Methods: Alzheimer's disease (AD) was induced in the male Wistar rats by intracerebroventricular
injection of amyloid beta peptide 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3)
and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ). The Morris
water maze was used to screen the successful establishment of the memory impairment model of
rats. The screened successful model rats were randomly divided into a model group and three
groups of three different doses of the drug (SSF). Rats in the drug group were treated with 35, 70,
and 140 mg/kg of SSF for 43 days. The Eight-arm maze was used to measure the spatial learning
and memory abilities of the rat, including working memory errors (WME) and reference memory
errors (RME). Immunohistochemistry was used to detect the expression of BrdU, an indicator of
neuronal proliferation, in the hippocampal gyrus of rats. The mRNA and protein expressions of
TRKB, PI3K, AKT, P-AKT, and IGF2 in the PI3K-AKT-CREB signaling pathway in the
hippocampus and cerebral cortex of the rats were determined by quantitative real-time PCR
(qPCR) and Western blotting methods.
Results: Compared to the sham group, the spatial memory ability of rats with composited Aβ was
decreased, the number of WME and RME (P < 0.01) was increased, the expression of BrdU
protein (P < 0.01) in the hippocampal gyrus was reduced, the mRNA and protein expression levels
of TRKB, AKT, and IGF2 (P < 0.01, P < 0.05) in the hippocampus and cerebral cortex were lowered,
and the mRNA expression level of PI3K (P < 0.01) in the cerebral cortex and the protein expression
level of PI3K (P < 0.01) in the hippocampus were augmented. However, compared to the model
group, the three-doses of SSF improved memory disorder induced by composited Aβ, reduced the
number of WME and RME, increased the expression of BrdU protein in the hippocampal gyrus, and
differently regulated the mRNA and protein expressions in composited Aβ rats.
Conclusion: SSF improved memory impairment and neurogenesis disorder induced by composited
Aβ in rats by activating the PI3K-AKT-CREB signaling pathway and up-regulating the mRNA and
protein expressions of TRKB, PI3K, AKT, CREB, and IGF2.
