Armillaria mellea fermentation liquor ameliorates p‐chlorophenylalanine‐induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats

In China, Armillaria mellea (Vahl) P. Kumm. has been used as a folk medicine to treat insomnia for several hundred years. However, the underlying mechanisms involved are currently unknown. In this study, the anti-insomnia efficacy of A. mellea fermentation liquor (AFL) was evaluated in p-chlorophenylalanine-induced insomnia rats by measuring the serotonergic systems and gut microbiota. Our results demonstrate that all doses of AFL significantly reduced locomotor activity and alleviated decreasing weights in insomnia rats. Further, AFL exhibited better sedative effects by reducing sleep latency and increasing sleep duration in pentobarbital-treated rats. AFL treatment also elevated serum glutathione peroxidase and superoxide dismutase levels, while reducing serum interleukin-6, tumor necrosis factor-α, and interleukin-1β levels. Furthermore, AFL alleviated insomnia by enhancing 5-hydroxytryptamine content and the expression 5-HT_1A and 5-HT_2A receptor in the hippocampus. Meanwhile, AFL treatment normalized the composition of gut microbiota in insomnia-model rats, while increasing relative abundance of Lachnospiraceae, Ruminococcaceae, and Saccharimonadaceae restores the gut microbial ecosystem altered in insomnia rats. The experiments show that A. mellea alleviated insomnia by modulating serotonergic system and gut microbiota. PRACTICAL APPLICATIONS: Insomnia has become a serious health issue of global concern. As a well-known traditional Chinese medicine, Armillaria mellea has been clinically employed in the treatment of insomnia for centuries in Asia with significant efficacy. In the present study, we firstly reported A. mellea fermentation liquor potentially relieved insomnia rats by alteration of gut microbiota and serotonergic systems and could guide future clinical studies. As a popular edible and medicinal mushroom, A. mellea also can be potentially used in the development and production of novel food products in the future.