Research progress of Lycium barbarum polysaccha-ride in preventing and treating Alzheimer's disease / 中国药理学与毒理学杂志

ABSTRACT

Alzheimer's disease(AD)is a neurode-generative disease with insidious onset and progressive development.In recent years,the prevalence of AD has shown a linear upward trend.At present,its pathogene-sis is not clear.Lycium barbarum polysaccharide(LBP)is one of the main effective components extracted from the dried ripe fruit of Lycium barbarum L.,a solanaceae plant.It has many pharmacological effects such as anti-aging,anti-oxidation,anti-fibrosis,anti-inflammation,neu-roprotection and immunomodulation.LBP has been widely studied in the field of prevention and treatment of AD because of its good anti-aging and neuroprotective effects.Its prevention and treatment mechanism mainly includes the following points① Regulating the apoptosis of nerve cells.Studies have shown that the signal pathway com-posed of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)participates in a series of processes such as the growth,proliferation and apoptosis of neurons and plays an important regulatory role.LBP can reduce the number of cell apoptosis,increase the expression levels of autophagy protein Beclin1 and microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and decrease the expres-sion levels of p-Akt and phosphorylated mammalian target protein of rapamycin(p-mTOR),which indicates that Lycium barbarum polysaccharide can prevent and treat AD by inhibiting PI3K/Akt/mTOR pathway and improv-ing the autophagy level of cells.②Inhibition of amyloid β-protein(Aβ)production.Aβ is the main component of senile plaque,which is regarded as the main biomarker of AD.It is found that the neurotoxicity of Aβ plays a role by increas-ing the influx of Ca2+ mediated by N-methyl-D-aspartate receptor in the process of signal transduction in the brain,and then generating reactive oxygen species(ROS)and apoptosis signals.LBP can promote autophagy of HT22 cells by inhibiting PI3K/Akt pathway,which has a protec-tive effect on Aβ-induced toxicity.③ Inhibit the produc-tion of inflammatory cytokines.In the pathogenesis of AD,microglia are activated when they feel pathological accumulation of Aβ,and then cell surface immune and adhesion molecules such as cluster of differentiation 45(CD45),CD40,CD36 and integrins are activated,thereby recruiting Src family kinases and activating MAPK path-way,leading to over-expression of proinflammatory fac-tors.A large number of cytokines and chemokines are produced,which may lead to synapse damage and loss.For example tumor necrosis factor-α(TNF-α)can induce neuronal apoptosis and injury.The production of interleu-kin,and other cytokines and chemokines may also lead to microglia activation,astrocyte proliferation,and further secretion of proinflammatory factors and amyloid deposi-tion,thus making the neuroinflammatory cascade perma-nent.LBP can down-regulate the expression of TNF-α and IL-1β genes,reduce the level of intracellular ROS,and improve the learning and memory ability of AD patients.In this paper,the mechanism of Lycium barbarum polysaccharide in preventing and treating AD is reviewed,in order to provide basis for drug development and clini-cal application.