Effects of Dangshen Yuanzhi Powder on learning ability and gut microflora in rats with memory disorder

Abstract

Ethnopharmacological relevance: Yuanzhi Powder is a commonly used traditional Chinese medical formulae for its potency in enhancing memory and learning. In clinical practice, Yuanzhi Powder is a classic formula in TCM to treat amnesia of the type "deficiency of Qi, turbid phlegm harasses the head and eyes, and stagnation of phlegm converting into the fire". Our previous study showed that Yuanzhi Power, used together with Codonopsis Radix (Dangshen Yuanzhi Power, DYP), could improve learning and memory ability in animals with memory disorder (MD) and its efficacy is superior or equivalent to that of the Yuanzhi Power.

Aim of study: This study aimed to explore the regulatory mechanism of DYP through the "bacteria-gut-brain axis".

Materials and methods: The SD rats were divided randomly into control, model, positive, DYP-L, and DYP-H groups. Except for the control group, the rats were intraperitoneally injected with D-Gal (400 mg/kg) and gavaged with aluminum chloride (200 mg/kg) every day for 50 days. The rats in the DYP group were gavaged with DYP (6.67 and 13.34 g/kg, respectively) from the 15th day, once a day. The rats in the positive group were similarly administrated with piracetam (0.5 g/kg). The rats' bodyweight was recorded from the 16th day. The learning and memory ability of animals was tested by Morris water maze. The levels of MCP-1, NF-L, NSE, and TNF-α in serum were determined by Elisa kit, while the histopathology of duodenum and colon tissues was examined by H & E staining. The diversity of intestinal flora was sequenced and analyzed. In order to reveal the role of intestinal flora in DYP treatment of MD, the intestinal flora composition and the correlation analysis of intestinal flora and the above biochemical indexes were investigated. The intestinal flora function and biological metabolic pathways were predicted and analyzed by the KEGG database.

Results: The MD animals' learning and spatial memory ability decreased significantly, compared with the normal group, accompanied by weight increase and intestinal flora disorder. DYP can improve the learning and memory ability of MD animals, and its efficacy may exert through the following ways: (i) callback the abnormal biochemical indexes of MCP-1, NF-L, NSE, and TNF-α; (ii) decreasing the relative ratio of Firmicutes/Bacteroidetes and repairing the pathology of MD animal intestinal mucosa; and (iii) the regulation of DYP on biochemical blood indexes of MD animals was significantly correlated with the regulation of intestinal flora; (iv) DYP rats showed a strong correlation between cognitive ability improvement and bodyweight loss; (v) besides, DYP could also regulate the metabolic pathways of carbohydrate, amino acid, nucleotide, and energy by affecting related biological functions.

Conclusions: The results supported that DYP can improve MD animals' learning and memory ability by restoring the intestinal flora disorder and callback the abnormal biochemical indexes in serum, closely related to the "bacteria-gut-brain axis".

Keywords: Brain-gut axis; Dangshen yuanzhi power (DYP); Intestinal flora; Memory disorder (MD); Obesity.