ABSTRACT
Alzheimer's disease （AD） is a neurodegenerative disease. With the acceleration of aging process， the number of AD patients increases year by year. This threatens the health and even life of patients， and causes heavy economic burden and mental pressure to patients， families and society. In traditional Chinese medicine （TCM）， AD belongs to the category of dementia， and tonifying kidney is the main treatment. Based on the basic theory of TCM and combined with clinical manifestations of AD， AD is closely correlated with liver and spleen. Therefore， "simultaneous regulation of three Yin" of liver， spleen and kidney will be an important way for the prevention and treatment of AD. Hei Xiaoyaosan， a representative prescription of "simultaneous regulation of three Yin" of liver， spleen and kidney， has theoretical， experimental and clinical basis in preventing and treating AD. Modern studies have shown that neurofibrillary tangle formed by tau hyperphosphorylation is a main pathological feature of AD， and trimethylamine oxide （TMAO） is closely related to tau hyperphosphorylation. Therefore， regulating TMAO metabolism to inhibit tau hyperphosphorylation is a new target for the prevention and treatment of AD. On the basis of the above theory and previous studies， this paper put forward the hypothesis that Hei Xiaoyaosan regulates the trimethylamine（TMA）/heparin monooxygenase 3（FMO3）/TMAO metabolic pathway of intestinal flora through "simultaneous regulation of three Yin" of liver， spleen and kidney， and then inhibits tau hyperphosphorylation in brain hippocampus， thereby protecting nerve cells， improving learning and memory， and preventing AD. This paper explored the role and mechanism of Hei Xiaoyaosan in the prevention and treatment of AD from the perspective of inhibiting tau hyperphosphorylation by regulating the TMA/FMO3/TMAO metabolic pathway of intestinal flora， which provided new ideas and strategies for in-depth study of Hei Xiaoyaosan in the prevention and treatment of AD.
ABSTRACT
Objective To investigate effects of angelica polysaccharide on learning and memory abilities, Ach, ChAT, AChE, SOD, MDA in serum, APP and Aβ1-42 in hippocampus in model rats with Alzheimer disease (AD); To explore the mechanism of angelica polysaccharide for the treatment of AD. Methods Seventy SPF Wistar rats were selected for learning and memory ability by water maze. 10 rats were randomly selected (half female and half male) as sham-operation group, and the others were injected with Aβ25-35 by stereotatic techniques, copying AD model rats. 50 rats for learning and memory ability by water maze were successfully divided into model group, positive group, angelica polysaccharide low-, medium-, and high-dose groups, with 10 rats in each group. Rats in model group and sham-operation group were given normal saline for gavage, while rats in medication groups were given relevant medicine for gavage, 2 mL/(100 g?d), for 28 d. The learning and memory ability of rats in each group was tested by Morris water maze during 25-28 days, and the contents of Ach, ChAT, AChE, SOD, MDA in serum and APP and Aβ1-42 in hippocampus were determined. Results Compared with the sham-operation group, the escape latent period of model group was significantly prolonged in place navigation experiment; the target quadrant time was shortened; the latent time for the first time to reach the original escape platform was longer in spatial probe test; the residence time of crossing the original platform position and the target quadrant was shorter; the levels of Ach, the activity of ChAT and SOD in serum decreased; the levels of MDA, the activity of AChE in serum increased; the levels of APP and Aβ1-42 in hippocampus increased, with statistical significance (P<0.05, P<0.01). Compared with model group, the escape latent period of each medication group was shortened in different degrees after the intervention treatment; the residence time of target quadrant was prolonged; the latent time for the first time to reach the original escape platform was shortened; the number of cross platform increased; the levels of Ach, the activity of ChAT and SOD in serum increased; the levels of MDA and the activity of AChE in serum decreased; the levels of APP and Aβ1-42 in hippocampus significantly decreased, with statistical significance (P<0.05, P<0.01). Conclusion Angelica polysaccharide may effectively improve the learning and memory of ability of AD model rats to improve anti-free radical oxidation and promote Aβ metabolism and promote learning and memory ability of AD model rats, which have some preventive and therapeutic effects on AD.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of Xiaoyao Powder (XP) and its compatible prescriptions on the ethology, morphology, and activities of neurotransmitters, thus exploring their effects and mechanism in preventing and treating D-galactose induced Alzheimer's disease (AD) model mice, and clarifying the compatibility mechanism for soothing Gan, nourishing blood, and invigorating Pi.</p><p><b>METHODS</b>Sixty SPF mice were randomly divided into the blank control group, the model group, and the XP group, Shugan Jianpi group (SJ), Shugan Yangxue group (SY), and Jianpi Yangxue group (JY), 10 in each group.The AD mouse model was prepared by peritoneal injecting D-galactose. Meanwhile, mice in the blank control group and the model group were administered with physiological saline (at the daily dose of 24 mL/kg) by gastrogavage. Mice in the XP group (2.485 g/kg), the SY group (1.136 g/kg), the SJ group (1.775 g/kg), and the JY group (2.059 g/kg) were administered with corresponding medicated decoction by gastrogavage, with the gastric volume of 24 mL/kg. On the 41st day the training of capability for learning and memory was started. On the 42nd day capability for learning and memory was tested. The brain tissue was cut. One half was used to determine the contents of homogenate acetyl cholinesterase (AchE), choline acetyltransferase (ChAT), and monoamine oxidase (MAO).Another half was used to carry out morphological observations.</p><p><b>RESULTS</b>The capability for learning and memory could be improved and the latency time could be lowered in all the treatment groups. Besides, the homogenate AchE and MAO could also be elevated, ChAT could be lowered; the morphology, number, and distribution of neurons could be improved. But the improvement of ethology, morphology, and activities of neurotransmitters were most obviously seen in the XP group.</p><p><b>CONCLUSIONS</b>XP could improve the ethology, morphology, and activities of neurotransmitters, and showed better effects on prevention and treatment of AD. The rationality of compatibility methods and combination thinking ways of soothing Gan, nourishing blood, and invigorating Pi were clarified.</p>