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We investigated the inhibitory effect of active hexose correlated compound (AHCC) on muscle atrophy in hindlimb-suspended rats. Twenty-four six-week-old male Sprague-Dawley rats were randomly divided into three groups: the control sedentary group (CS, n = 8), the hindlimb-suspended group (HS, n = 8), and the hindlimb-suspended and AHCC-supplemented group (HSA, n = 8). Hindlimb suspension and AHCC supplementation were performed for two weeks. The HSA group was treated with AHCC (1 g/1 kg of body weight (BW)) orally in 0.3 mL of PBS solution, while the HS group received the vehicle (PBS solution) only. After two weeks, the cross-sectional area (CSA) of the HS and HSA groups decreased by approximately 36% (p < 0.05) and 19%, respectively, compared to the CS group. In addition, myonuclear numbers of the HS and HSA groups and the extensor digitorum longus (EDL) muscle weight of the HS group decreased 30% (p < 0.05) and 18%, respectively, compared to the CS group. AHCC supplementation increased the phosphorylation of pAkt/Akt in the HSA group compared to the HS group (p < 0.05). Furthermore, Fbx32 and MuRF1 protein expression in the HSA group recovered to the level of the CS group. Based on these results, AHCC supplementation may have a positive role in the prevention of muscle atrophy via Akt activation in hindlimb-suspended rats. [ABSTRACT FROM AUTHOR]