Yishen Huazhuo Decoction Induces Autophagy to Promote the Clearance of Aß1-42 in SAMP8 Mice: Mechanism Research of a Traditional Chinese Formula Against Alzheimer's Disease.

BACKGROUND: Studies have found that autophagy could promote the clearance of Aß. 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, Aß, 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 that 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 Aß1-42 protein, improve the expression of Beclin-1 and p-Bcl2 proteins, reduce mTOR and p62 proteins. CONCLUSION: YHD could induce autophagy initiation, increase the formation of autophagosomes and autolysosome, promote the degradation of autophagy substrates, thereby regulating autophagy, and promoting the clearance of Aß1-42 to improve memory impairment in SAMP8 mice.

[Analysis on acupoint selection rules of acupuncture for Alzheimer's disease based on complex network].

OBJECTIVE: To explore the acupoint selection rules of acupuncture for Alzheimer's disease (AD) in modern clinical practice by complex network technology. METHODS: The relevant articles of clinical trials were retrieved from CNKI published before December 2017. Using Microsoft Excel 2010, the database was established. Using Gephi 0.8.2 software, the complex network mode was built and its topological structure was analyzed. RESULTS: Finally, 81 articles were eligible and 114 acupoint prescriptions were extracted. The constructed complex network of acupoint prescriptions for AD was characteristics as small world effect and scale-free property, the crucial acupoints included Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Yintang (GV 29), Shenmen (HT 7), Shenting (GV 24), Zusanli (ST 36), Fenglong (ST 40) and Taichong (LR 3). In acupoint combination, Baihui (GV 20), Neiguan (PC 6), Shenmen (HT 7) and Sanyinjiao (SP 6) were the most common, and the combination of the distal and nearby points was predominant. Using k-core for acupoint optimization, 29 core acupoints were screened and they were mostly located on the governor vessel and the head and neck, with the highest use frequency. 82.76% of acupoints were specific acupoints and the influential points were dominant. Using community structure partition, these acupoints were classified into two groups, i.e. deficiency syndrome and excess syndrome. CONCLUSION: The selection of local acupoints is the first choice in acupuncture treatment for AD. The combination of distal and nearby points is the most common and the special points are the core. In clinical practice, the great consideration is provided on mind regulation, integration of disease and symptoms, the mutual treatment of the primary and the secondary as well as the deficiency and the excess.