Total ginsenoside and Acorus tatarinowii volatile oil co-administration reverses learning memory deficits, reduces Aβ42 and AChE levels, and downregulates the PI3K/Akt/mTOR/Beclin-1 autophagic pathway in APP/PS1 double transgenic mice

Abstract

Ethnopharmacological RelevanceThe combined application of ginseng and Shichangpu comes from the nootropic prescription—Dingzhi Xiaowan. One of the main effective components of ginseng is saponins. Studies have reported that its total saponins have significant neuroprotective effects, especially in anti-neuro-inflammation and anti-cognitive impairment. Shichangpu is a traditional Chinese medicine commonly used in clinical treatment of mental disorders such as dementia, amnesia, and epilepsy. One of the main active ingredients of Acorus tatarinowii is volatile oil, and research reports that its volatile oil also has a good neuroprotective effect. Previous research by the research team has shown its potential efficacy against Alzheimer's disease (AD). Aim of the studyAt present, the pathogenesis of Alzheimer's disease (AD) is not yet clear and the current treatment methods can only relief the related symptoms of AD. Our previous research found that the volatile oil of Acorus tatarinowii and components of ginsenosides, such as Rd, Rh2 and Rg1 can improve the learning and memory ability of AD mice. However, the effect and mechanism of volatile oil of Acorus tatarinowii combined with total ginsenosides on APP/PS1 double transgenic mice are still unknown. Materials and methodsIn this study, the effects of total ginsenoside and Acorus tatarinowii volatile oil co-administration on behavioral tests, amyloid β 42 (Aβ42) and acetylcholinesterase (AChE) levels, p-Akt, p-mTOR, LC3B, Bcl-2 and p62 expressions were investigated in APP/PS1 double transgenic mice. Furthermore, the PI3K/Akt/mTOR autophagic pathway was also studied and the structure of hippocampal neurons was observed. ResultsThe results showed that co-administrated treatment improved the learning and memory ability of mice in the water maze, passive avoidance and step-down tests, the swimming time and error times were shorten and incubation period was prolonged. And Aβ42 and AChE levels decreased, LC3B and Beclin-1 expressions declined, and number of autophagosomes reduced in the hippocampus of the APP/PS1 double transgenic mice, in contrary, the change of p-Akt, p-mTOR, P62 and Bcl-2 expressions were increased in the co-administrated treated mice compared with the untreated mice. We deduced that co-administrated therapy may firstly upregulate expressions of p-Akt, p-mTOR, P62 and Bcl-2, and then indirectly decrease the expression of LC3B and Beclin-1. ConclusionCollectively, all data indicated that total ginsenoside and Acorus tatarinowii volatile oil co-administration may play an autophagy inhibited role in preventing AD development by the PI3K/Akt/mTOR pathway.