부산대학교 도서관

Background:Panax notoginseng saponins (PNS) is extracted from Sanqi (Panax notoginseng), which is a valuable herb and has been widely used in traditional Chinese medicine for the treatment of cerebrovascular diseases and pain. PNS has been proved to promote blood circulation and angiogenesis by inhibiting platelet aggregation. In our previous study, PNS accompanied with geniposide can prevent Alzheimer's disease (AD). However, the efficacy of PNS and its potential mechanism in AD remain unclear. Methods: Amyloid precursor protein/presenilin-1 (APP/PS1) transgenic (Tg) mice were used as AD-like animal models. Wild-type mice and APP/PS1 transgenic were administrated with saline solution while mice in PNS treatment group were administrated with PNS at a dosage of 17 mg/kg/day for three months. Morris water maze (MWM) was applied to evaluate the spatial learning and memory and step-down test was used to evaluate the cognitive function. 1％Thioflavin-S staining was used to calculate the average number amyloid plaques in cortex and hippocampus. CD31 staining was detected to observe the density of cerebrovascular in hippocampus areas and CD105 staining was further detected to evaluate angiogenesis. Laser Doppler PeriFlux 5000 was further measured the change of cerebrovascular blood flow. ChemDraw was used to draw the molecular structures of five main ingredients of PNS. AlzPlatform were used to estimate the potential targets of PNS. Results: By a bench of behavioral tests, PNS showed a better tendency in proving cognitive functions. In addition, the amyloid plaques in both cortex and hippocampus were significantly reduced after PNS intervention (P<0.05 and P<0.001 respectively). Furthermore, the density of cerebrovascular in the hippocampus areas was increased under PNS administration (P < 0.001), which accompanied with angiogenesis in dentate gyrus areas and cerebrovascular blood flow promotion (P<0.05). By AlzPlatform docking serve, we screened five major ingredients of PNS—R1, Rd, Rb1, Re and Rg1. These screening data suggested that vascular related proteins could be the one of potential targets of PNS, such as platelet activating factor receptor and vasopressin V1a receptor. Conclusion:By modulating cerebrovascular function, PNS can reduce the deposition of amyloid plaques and exhibit the role of neuroprotection in a preventive strategy.