## 3 Pharmacological Properties of GP
### Neuroprotective Effect  
#### 3.4.1 Effect on Alzheimer's Disease  
Alzheimer's disease (AD) is a common degenerative neurological disease, which is mainly manifested in the severe decline of cognitive function and memory. The characteristic pathological changes of AD include extracellular senile plaques formed by beta-amyloid protein (A\(\beta\)) deposition, neurofibrillary tangles formed by Tau protein hyperphosphorylation, and neuronal loss accompanied by glial cell proliferation. There were many theories about the pathogenesis of AD, including abnormal deposition of A\(\beta\), Tau protein hyperphosphorylation, and so on [76]. At present, there was no specific cure drug, and only symptomatic treatment and therapeutics to delay the progression of AD were given to AD patients. A\(\beta\) abnormal deposition was a crucial factor that drives AD pathogenesis, which was associated with neuroinflammation, oxidative stress, cell apoptosis and autophagy, etc. GPS could improve the learning and memory ability in dementia mice induced by D-galactose combined with sodium nitrite and aluminum trichloride, and the mechanism underlying might be related to the reduced oxidative damage and A\(\beta\) expression in brain tissues. Compared with the model group, the activity of SOD and GSH-Px were significantly increased, and the level of MDA was significantly decreased in brain tissues of the GPS group (250 mg/kg). In addition, the expression of A\(\beta\)42 decreased by treatment with GPS [77]. Under normal circumstances, microglial cells were in a static state, which might be activated into a classic activated state (M1 state) or alternative activated state (M2 state) when the body was in a pro-inflammatory environment for a long time. The former was harmful; in contrast, the latter was beneficial. A high level of A\(\beta\) in the brain could activate microglial cells to secrete pro-inflammatory factors and eventually develop into chronic inflammation. Treatment with 50 mg/L GPS for 24 h could attenuate A\(\beta\)-induced inflammation by reducing microglial activation and shifting microglial M1 to M2 state, and the process might be mediated by suppressors of cytokine signaling 1 (SOCS1) [78]. GPS also could improve cognitive dysfunction and chronic inflammation caused by injecting lipopolysaccharide in the hippocampus. GPS treatment (25, 50, and 100 mg/kg) for 21 days significantly decreased pro-inflammatory mediators such as IL-6, IL-1\(\beta\), and NF-kB levels in the brain [79]. Pretreatment with GPS could effectively inhibit the A\(\beta_{1-40}\)-induced increase in inducible nitric oxide synthase (iNOS) expression and cell apoptosis. Compared with A\(\beta_{1-40}\) group, the growth condition of cells incubated with GPS was improved obviously, the number of neurons was increased, and the synapses between adjacent neurons were more and compact [80]. [PERSON] et al. investigated the neuroprotective effect against A\(\beta\)-induced cytotoxicity of a purified polysaccharide GPP1 in PC12 cells. The results showed that GPP1 exerted its protective effect via inhibiting oxidative stress and suppressing the mitochonddrial apoptotic pathway [81]. Phytoestrogens had been proved to be protective against A\(\beta\)-induced neurotoxicity and regarded as a relatively safe agent for AD treatment. GP-17, as a novel phytoestrogen isolated from GP, had reported its neuroprotective effect [82, 83]. GP-17 promoted the autophagy-based elimination of A\(\beta\) and prevented the formation of A\(\beta\) plaques in the hippocampus and cortex of APP/PS1 mice [82]. GP-17 exerted protective effect against A\(\beta_{25,35}\)-induced neurotoxicity in nerve growth factor-induced differentiation of PC12 cells, including oxidative stress, apoptosis, and autophagic cell death, which might be related to estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3\(\beta\), and activation of nuclear factor-erythroid 2-related factor 2/antioxidant responsive element/heme oxygenase 1 (Nrf2/ARE/HO-1) pathways [83].