3, 14, 19-Triacetyl Andrographolide alleviates the cognitive dysfunction of 3 x Tg-AD mice by inducing initiation and promoting degradation process of autophagy
Phytotherapy research : PTR(2023)
摘要
The present study aims to investigate the cognition-enhancing effect of 3, 14, 19-Triacetyl andrographolide (ADA) on learning and memory deficits in 3 x Tg-AD mice and to explore its underlying mechanism. Eight-month-old 3 x Tg-AD mice and C57BL/6J mice were randomly divided into three groups, namely wild-type group, 3 x Tg-AD group, and 3 x Tg-AD+ADA group (5 mg/kg, for 21 days, i.p.). We found that ADA significantly improved learning and cognition impairment, inhibited the loss of Nissl body, and reduced A beta load in the brains of 3 x Tg-AD mice. In addition, ADA enhanced the levels of PSD95 and SYP, which were closely associated with synaptic plasticity. Accumulated autophagosomes, LC3II, and P62 in hippocampus and cortex of 3 x Tg-AD mice were decreased by ADA treatment. Furthermore, ADA administration further down-regulated the expressions of p-AKT and p-mTOR, reduced the level of CTSB, and increased the co-localization of LC3 and LAMP1 in the brains of 3 x Tg-AD mice, implying that ADA-induced autophagy initiation and also promoted the degradation process. In A beta(25-35)-induced HT22 cells, ADA displayed similar effects on autophagy flux as observed in 3 x Tg-AD mice. Our finding verified that ADA could improve synaptic plasticity and cognitive function, which is mainly attributed to the key roles of ADA in autophagy induction and degradation.
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关键词
3,14,19-triacetyl andrographolide,Alzheimer's disease,AKT,mTOR pathway,autophagy,lysosome
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