Banxia Xiexin Decoction Ameliorates Cognition Deficits by Activating Autophagy-induced Clearance of Aβ in APP/PS1  Mice

The purpose of this study aimed to explore the potential mechanism of the Chinese herbal compound Banxia Xiexin decoction (BXD) concerning autophagy in the treatment of Alzheimer’s disease (AD). Amyloid-β (Aβ) clearance of AD mice is weakened by autophagy dysfunction, which is caused by excessive Mammalian target of rapamycin (mTOR), the primary negative regulator of autophagy signaling pathway. Therefore, resuming normal autophagic modulation efficiency may promote the clearance of Aβ, which can serve as a potential therapeutic strategy for AD. Many active components of BXD exert the therapeutic effects on AD to some extent, and our previous research demonstrated that treatment with BXD improves cognitive ability in APP/PS1 mice. In this study, BXD alleviates the memory and cognitive impairment in the Morris water maze (MWM) test. Immunohistochemistry (IHC) and western blot (WB) results revealed that BXD reduces hippocampal Aβ 42 load in APP/PS1 mice. Furthermore, transmission electron microscopy(TEM) showed that BXD activates autophagy by improving the ultrastructure of autophagosomes. IHC, WB, and RT-qPCR results indicated that expression of autophagy-related proteins (Beclin1 and LC3) and their mRNAs, was increased in response to BXD intervention. Finally, WB data demonstrated that BXD improved the classical pathway of autophagy by decreasing the expression of mTOR and p-mTOR, and increasing the expression of PI3K, p-PI3K, Akt, and p-Akt in APP/PS1 mice. We conclude that BXD improves cognitive levels of APP/PS1 mice, possibly by acting on the classic autophagy pathway, affecting protein expression of PI3K, Akt, mTOR, and autophagy proteins (Beclin1 and LC3), then reducing the accumulation of Aβ 42 .