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.