Yishen Huazhuo Decoction Induces Autophagy to Promote the Clearance of Aβ1-42 in SAMP8 Mice: Mechanism Research of a Traditional Chinese Formula Against Alzheimer’s Disease

Abstract

Background: Studies have found that autophagy could promote the clearance of Aβ. To promote and maintain the occurrence of autophagy in Alzheimer's disease (AD) might be a potential way to reduce neuronal loss and improve the learning and memory of AD. Objective: To investigate the possible mechanisms of Yishen Huazhuo Decoction (YHD) against AD model. Methods: Forty 7-month-old male SAMP8 mice were randomly divided into model (P8) group and YHD group, 20 in each group, with 20 SAMR1 mice as control (R1) group. All mice were intragastrically administered for 4 weeks, YHD at the dosage of 6.24g/kg for YHD group, and distilled water for P8 group and R1 group. Morris water maze (MWM) test, Nissl’s staining, TEM, TUNEL staining, immunofluorescence double staining, and western blot analysis were applied to learning and memory, structure and ultrastructure of neurons, autophagosome, apoptosis index, Aβ, LAMP1, and autophagy related proteins. Results: The escape latency time of YHD group was significantly shorter on the 4th and 5th day during MWM test than those in P8 group (P=0.011, 0.008<0.05), and the number of crossing platform in YHD group increased significantly (P=0.02<0.05). Nissl’s staining showed that the number of neurons in YHD group increased significantly (P<0.0001). TEM showed in YHD group, the nucleus of neurons was slightly irregular, with slightly reduced organelles, partially fused and blurred cristae and membrane of mitochondria. The apoptosis index of YHD group showed a decreasing trend, without statistically significant difference (P=0.093>0.05), while Caspase3 expression in YHD group was significantly lower (P=0.044<0.05). YHD could promote the clearance of Aβ1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. Conclusions: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby to regulate autophagy, thereby to promote the clearance of Aβ1-42 to improve memory impairment in SAMP8 mice.

Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics

“…53 Moreover, in the SAMP8 mouse AD model, treatment with Yishen Huazhuo decoction enhanced Aβ removal via upregulation of BECN1 and downregulation of MTORC1 and promoted autophagosome formation, resulting in enhanced autophagy. 54 In sum, adaptive (mild) autophagy is a cytoprotective mechanism that mitigates AD, whereas dysfunctional autophagy promotes neuronal injury and AD.…”

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer’s Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

“…YZP is composed of herbs like Polygala tenuifolia Willd (Yuanzhi), Acorus tatarinowii (Shichangpu), Coptis chinensis Franch (Huanglian), Poria (Fuling), and Ginseng Radix et Rhizoma (Renshen). Yuanzhi, Huanglian, and Renshen have been widely investigated for their neuroprotective properties, such as anti-Aβ aggregation, antitau protein, strengthening the central cholinergic system, and encouraging neuronal proliferation in AD [5][6][7]. Shichangpu may have anti-inflammatory and neuroprotective properties [8].…”

Analysis of the Composition and Anti-Rheumatoid Arthritis Mechanism of Qintengtongbi Decoction Based on Network Pharmacology

“…6 Traditional Chinese Medicine (TCM) has been proved to be a great contributor to life quality and diseases treatment. [7][8][9] It is widely recognized by westerners as a substitute and supplement for western medicine in the treatment of diseases. 10 So far, TCM has attracted more and more attention from all over the world, thanks to its outstanding clinical efficacy, especially when combined with western medicine.…”