The early intervention of geniposide and PNS combination modulated Aβ production and synaptic plasticity in young APP/PS1 transgenic mice

Abstract

BackgroundAlzheimer's disease (AD) is a common neurodegenerative disease with age-related, which accounts for nearly 80% of dementia. Accompanied with aging population worldwide and clinical failures in AD drugs, early prevention and diagnosis are under main concern. Traditional Chinese medicine (TCM) has a long history in the prevention of cognition declines. In clinic, the combination of geniposide and Panax notoginseng saponin (PNS) is clinically efficacious in the treatment of ischemic cerebral stroke and vascular dementia. In vivo, under a preventive strategy, the combination can improve spatial learning and memory and reduce amyloid plaques in a variety of AD-like animal models. MethodsIn order to illustrate the neuroprotective role of geniposide and PNS combination under the early intervention strategy, we medically administrated at one-month age of APP/PS1 transgenic mice for three months. The morphology of pyramidal neurons in hippocampus CA1 was observed after Hematoxylin and Eosin staining (HE staining) and the dendritic spines in hippocampus CA1 area are by Golgi silver staining. Thereafter we detect the level of Aβ1-40 and Aβ1-42 in hippocampus and in cortex by ELISA. In addition, western blotting was used for further understanding the effects of geniposide and PNS combination in APP/PS1 transgenic mice. ResultsWe found that the ratio of Aβ 1−42 / Aβ 1−40 in both cortex and hippocampus was significantly decreased under the treatment; secondly, the combination significantly increased dendrite spine density in hippocampus CA1 areas, and increased the protein level of PSD-95 (synaptic functionrelated protein in post-synapse). ConclusionThese results indicated that geniposide and PNS combination modulated Aβ production and synaptic plasticity in the early stage of AD processing. BackgroundTraditional Chinese Medicine (TCM) has experienced more than 2000 years in oriental countries, followed by a general principle referring to that compatible components of different herbal decoction may jointly play a role in synergistically enhance curative efficacy or reduce adverse effects. In the 4 theory of TCM, the pathogenesis of dementia has been considered as the damage of brain collateral by toxins. Combined with the knowledge of AD pathological changes, inflammation, amyloid plaques could be the toxins in TCM, which resulted in the damage of synaptic plasticity and connections, and eventually leaded to cognition declines. Based on the theory, the formulae prescribed according to detoxification and collateral-dredging strategy has been administrated in dementia, such as the combination of geniposide (GP) and Panax notoginseng saponin (PNS). In clinic, the combination has been used in ischemic stroke patients and also whose memory declined [1]. GP is the main bioactive ingredient of Fructus Gardeniae, which is considered as a function of clearing away heat and toxic materials, also is regarded as diminishing inflammation in modern medicine [2,3]. PNS is the main bioactive ingredient of Panax notoginseng, which is...