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

Abstract

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 factorα, 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 applicationsInsomnia 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.

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

“…In previous studies, propionate induced the gene transcription of tyrosine hydroxylase, an enzyme involved in catecholamine biosynthesis ( Nankova et al, 2014 ; Dalile et al, 2019 ), which acts as a neurotransmitter in the center neuron system. Yao et al (2022) and Si et al (2022a) demonstrated a relationship between PCPA administration and dysbiosis in animals. Especially, the latter study showed that PCPA-induced 5-HT depletion affects gut microbiota in rodents.…”

Critical review of the phytochemical profiles and health-promoting effects of the edible mushroomArmillaria mellea

“…Discrepancies in findings between our study and others may be attributed to species-specific differences and methodological variations. 48 In conclusion, the experimental results affirm the potential of AM in alleviating insomnia by modulating serotonergic systems and gut microbiota. As a popular edible and medicinal mushroom, AM also holds promise for the future development and production of innovative food products.…”

“…Discrepancies in findings between our study and others may be attributed to species-specific differences and methodological variations. 48…”

Valerian essential oil for treating insomnia via the serotonergic synapse pathway

“…Compared to the normal control group, the body mass of rats in the modeling group was significantly reduced. Compared with the model control group, after 6 days of treatment with valerian volatile oil ( 33 ), the rats had a normal diet, regular circadian rhythm, and increased body mass, as shown in Figures 6A,B . These phenomena showed that valerian volatile oil had a certain effect on improving the insomnia of rats.…”