https://doi.org/10.1016/j.apsb.2026.07.023
This new article publication from
Acta Pharmaceutica Sinica B discusses how interactions between the investigational compound YZG-331 and the gut microbiota contribute to its sleep-promoting effects in mouse models of insomnia.
Gut microbes can influence both drug metabolism and the chemical signals involved in sleep regulation. YZG-331, a compound derived from research on the medicinal plant Gastrodia elata, has shown sedative and hypnotic effects, but the contribution of the gut microbiota to its activity remains incompletely understood. The authors of this article combined mouse experiments, metabolic profiling, microbial analysis, and bacterial gene-overexpression studies to investigate this relationship. In chemically induced and chronic restraint-induced models of insomnia, YZG-331 improved sleep-related measures and increased metabolites involved in the conversion of tryptophan to serotonin (5-HT). Depleting the gut microbiota substantially weakened its effects, supporting a role for intestinal microbes. Further investigations identified Lactobacillus reuteri and its enzyme ribonucleoside hydrolase RihC as contributors to the conversion of YZG-331 into the metabolite M2. The study also provided evidence that microbial hydroxylation of YZG-331 supports the tetrahydrobiopterin (BH4) cofactor system and tryptophan hydroxylase activity, helping to increase serotonin production. Both YZG-331 and M2 increased intestinal butyric acid levels, accompanied by changes in sleep-related signaling and improvements in intestinal barrier function. YZG-331 also improved sleep measures in mice receiving gut microbiota from people with insomnia, providing further support for the relevance of these interactions. These findings highlight how gut microbes may contribute to the metabolism and activity of a potential insomnia treatment. However, the animal experiments used only female mice, the metabolic and microbial analyses involved small samples, and the proposed hydroxylation mechanism remains preliminary. Studies in both sexes and in human cohorts are needed to validate the findings and clarify their clinical relevance.
Keywords: Insomnia, YZG-331, Gut microbiota, Tryptophan hydroxylase, 5-HT, RihC, Hydroxylation,
Lactobacillus reuteri
Graphical Abstract: available at
https://ars.els-cdn.com/content/image/1-s2.0-S2211383526004612-ga1_lrg.jpg
YZG-331 regulates tryptophan metabolism and 5-HT production pathways by the gut microbiota.
Lactobacillus reuteri plays a critical role in both the metabolic processes of YZG-331 and the biosynthesis of tryptophan-derived metabolites.
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The Journal of the
Institute of Materia Medica, the Chinese Academy of Medical Sciences and the
Chinese Pharmaceutical Association.
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CiteScore: 24.4
Impact Factor: 14.6 (Top 8 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 14.0
ISSN 2211-3835
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Hengtong Zuo, Qinglan Guo, Bin Zhao, Jinyue Lu, Ru Feng, Jingyue Wang, Jianye Song, Jingyu Jin, Jiachun Hu, Yi Zhao, Hui Xu, Tiefeng Yuan, Wanxia Wang, Yongmei Tu, Lingyu Wei, Yifan Zhao, Xiang Hui, Zhihao Liu, Li Sheng, Yan Li, Jianjun Zhang, Jinlyu Sun, Jiangong Shi, Yan Wang, Molecular mechanisms of YZG-331 ameliorated insomnia based on the gut microbiota–drug interaction, Acta Pharmaceutica Sinica B, Volume 16, Issue 10, 2026, Pages 6705–6730, ISSN 2211-3835,
https://doi.org/10.1016/j.apsb.2026.07.023