Abstract

Walnut kernel has been applied in daily diets for thousands of years with its memory enhancement effect. For further observing the effect of memory enhancement, the walnut kernel was extracted and separated into active parts, with the evaluation in mice. 30% ethanol elution from AB-8 macroporous resin showed a decreased escape latency time and increased cumulative time and crossing frequency through the Morris test. It also increased the latency time and decreased jumps in the step-down test. These results indicated the memory enhancement effect of the fraction. After further separation and purification, four compounds were acquired with tryptamine-like structures first found in the walnut kernel, and compounds III and IV were new ones. Compound III showed decreased escape latency time, increased cumulative time, increased crossing frequency through the Morris test, and increased latency time, decreased jumps in the step-down test. Compound III also alleviated acetylcholinesterase activity and promoted acetylcholine transferase activity. In silico docking and molecular dynamic studies displayed the most polar interactions of compound III on 5-hydroxytryptamine receptor 4 (5-HTR4) with the most polar interactions and the lowest binding energies, and anti-degeneration effect to monoamine oxidase A (MAO-A) with the high binding energy and sizeable steric hindrance. These results illustrated the memory enhancement of compound III in the walnut kernel, indicating more potential activities of tryptamine-like components and more applications for walnut kernel in clinical use or daily diets.

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