Objective To study the anti-anxiety effect of baicalein based on zebrafish model. Methods The zebrafish were divided into control group, model group, baicalein group and diazepam group. Except for the control group, all other groups underwent the induction of a zebrafish anxiety model through unpredictable chronic stress (UCS). After drug intervention, the behavior changes of zebrafish were evaluated through novel tank test. ELISA was used to measure the levels of stress response biomarkers cortisol and brain neurotransmitter serotonin 5-hydroxytryptamine (5-HT). qRT-PCR was employed to detect the gene expressions of tryptophan hydroxylase 2 (TPH2), a rate-limiting enzyme for 5-HT synthesis in brain tissue, 5-hydroxytryptamine 1ab receptors (5-HT_1abR), interleukin-1β (IL-1β), nuclear factor-κB (NF-κB), as well as intestinal IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and NF-κB. Western blotting was used to detect the protein expressions of 5-hydroxytryptamine 1A receptors (5-HT_1AR) in brain tissue. The composition of intestinal microbiota was analyzed using 16S rRNA microbial diversity sequencing technology. Results After UCS treatment, zebrafish exhibited anxiety-like behavior, with a decrease in the total number and diversity of intestinal microbiota species, and an increase in the proportion of Aeromonas. Compared with model group, after intervention with baicalein, the dwell time of zebrafish at the bottom of the tank was significantly reduced (P < 0.001), cortisol level was significantly decreased (P < 0.001), 5-HT level in brain tissue was significantly increased (P < 0.001), gene expression of TPH2 in brain tissue was significantly increased (P < 0.05), gene expressions of IL-1β, NF-κB in brain tissue and IL-1β, IL-6, TNF-α, NF-κB in intestine were significantly decreased (P < 0.05, 0.01, 0.001), the protein expression of 5-HT_1AR in brain tissue was decreased (P < 0.001), species richness and diversity of intestinal microbiota species were increased, the gene expression of 5-HT_1abR in brain tissue was significantly reduced in 2 mg/L baicalein group (P < 0.01), while the gene expression of 5-HT_1abR in brain tissue was significantly increased in 1, 4 mg/L baicalein groups (P < 0.05, 0.001). Conclusion Baicalein has a certain protective effect on UCS-induced anxiety-like behavior in zebrafish, which may be achieved by anti-inflammatory and regulating gut microbiota, inhibiting excessive production of cortisol in zebrafish, maintaining normal secretion of 5-HT, and exerting anti-anxiety effects.

baicalein  /  zebrafish  /  anxiety  /  inflammation  /  intestinal microbiota  /  cortisol  /  5-hydroxytryptamine