Chronic Administration of Anti-Stroke Herbal Medicine TongLuoJiuNao Reduces Amyloidogenic Processing of Amyloid Precursor Protein in a Mouse Model of Alzheimer's Disease

Composed of Ginsenoside Rg1 and Geniposide, the herbal medicine TongLuoJiuNao (TLJN) injection liquid has anti-inflammatory properties and can improve learning and memory in mice. Recently, TLJN has been used to treat the patients with cerebral ischemic stroke and vascular dementia, which significantly increase the risk of developing Alzheimer's disease (AD) in the early human beings. Although beneficial effects of TLJN have been reported in the vascular-associated brain disorders, the roles of TLJN in AD brains are still not clear. In this study, we chronically administered TLJN in amyloid precursor protein (APP) Swedish mutant transgenic mice (APP23) from 6 months old of age, which is at the onset of A beta plaques, to 12 months old. We found that TLJN significantly decreased A beta production and deposition in the brain of APP23 mice. Furthermore, we observed that TLJN down-regulated the levels and activity of beta-secretase 1 (BACE1) protein as well as the expression levels of gamma-secretase complex components: PS1, nicastrin and anterior pharynx-defective 1 (APH1) but not presenilin enhancer 2 (PEN2). The results suggest an inhibitory effect of TLJN on amyloidogenic APP processing by down-regulating the cleavage enzymes BACE1 and gamma-secretase.