The Therapeutic Effect And Mechanism Of Bacopaside Ⅰ Against Alzheimer’s Disease

Alzheimer’s disease（AD）is a one of the most common neurodegenerative diseasesworldwide. In clinic, its main the features are extracellular amyloid plaques andneurofibrillary tangles in cells, which both lead to the dysfunction of neuron and cell death.The pathogenesis of this disease is very complex and associated with multiple proteins. A fragment is the main neurotoxicity component of AD process. The accumulation of A cancause in the extracellular: the blockage of ion channels on nerve cells（;2）the destruction ofthe calcium homeostasis（;3）mitochondria oxidative stress（;4）impaired energy metabolismand abnormal glucose regulation, etc. The current clinical drugs on AD can’tfundamentally cure AD. Once stop using, AD will recur. At present, the lack of kinds ofdrugs currently available for treating AD, their limited targets and their adverse drugeffects in AD patients, encourage us to search for a new generation of drugs targeting otherpathways of AD.Many recent studies found that some natural products provide health benefits likeantipsychotic, antidepressant resist fatigue, anti-anxiety, anti-inflammatory, and antioxidant.These findings suggest that these natural products may be particularly beneficial to ADpatients because in late stages of AD progression, the patients exhibit series inflammation,oxidation, infections, etc, in addition to the cellular change. And the natural attribute ofnatural products makes them safer and with less adverse drug effects.Standardized extracts of Bacopa monniera（BME）have been shown to have awell-documented neuroprotective effect against cerebral ischemia, mental depression,anxiety and AD in chronic administration studies. But the mechanism of action is stillunclear. In this study, we evaluated the therapeutic effect of Bacopaside I（BS-I）, a majortriterpenoid saponin of BME on the neuropathology and cognitive impairment in APP/PS1transgenic mice and explored the possible mechanism from a biological systemsperspective. We found that the BS-I treatment significantly ameliorated learning deficits,long-term spatial memory retention and plaque load in Tg2576mice. We constructedBS-I’s therapeutic effect network by mapping the nodes according to their functionalcategories on the protein-protein interaction network based on the genomics andproteomics data. Because many of the top enrichment categories related to the processesand aspects of the immune system and phagocytosis are detected, we proposed that BS-Imay promote amyloid clearance via the induction of a suitable degree of innate immune stimulation and phagocytosis. Our study may help elucidate the neuroprotectivemechanism of BME and indicate natural saponins targeted to the immune system may offernew research avenues for the therapy of AD.