Abstract: The purpose of this study was to explore the effects of konjac glucomannan (KGM) with different molecular masses (1, 5 and 90 kDa) on cognitive dysfunction and brain oxidative stress in mice induced by a high-calorie diet. In this study, 90 mice were randomly divided into nine groups: normal diet (ND), negative control (ND + 1 kDa KGM, ND + 5 kDa KGM, and ND + 90 kDa KGM), high-fat and high-fructose diet (HFFD) model, intervention (HFFD + 1 kDa KGM, HFFD + 5 kDa KGM, and HFFD + 90 kDa KGM), and positive control (HFFD + KGM). Behavioral tests including open field, Y maze and Morris water maze tests were conducted to evaluate the learning and memory ability of mice. Meanwhile, the morphological changes of brain nerve cells were evaluated by pathological section, and the relative content of glutathione (GSH) and the relative activity of catalase (CAT) in brain tissue were determined by commercial kits. The results demonstrated that KGM, regardless of its molecular mass, could significantly improve the spatial working memory capacity of mice fed HFFD (P < 0.05). The total movement distance of mice in the 90 kDa KGM intervention group was significantly increased in the open field and water maze positioning navigation tests (P < 0.05), while supplementation of 1 kDa KGM significantly decreased the escape latency (P < 0.05) and significantly increased the number of times that mice crossed the platform location and the movement distance in the quadrant (P < 0.05). Immunohistochemical results showed that konjac glucomannan markedly inhibited the morphological abnormalities of hippocampal neurons in the mouse brain induced by HFFD. Similarly, 90 kDa KGM significantly increased the relative level of GSH (P < 0.05), and 1 kDa KGM significantly up-regulated the relative activity of CAT in mouse brain tissue (P < 0.05). These results indicated that konjac glucomannan with high molecular mass (90 kDa) can effectively enhance the spontaneous activity of mice, while konjac glucomannan with low molecular mass (1 kDa) can significantly improve the learning and memory ability of mice fed a high-calorie diet. The underlying mechanism may be related to the oxidative stress state in the brain.

Key words: konjac glucomannan; molecular mass; high-calorie diet; cognitive dysfunction; oxidative stress