The Volatile Oil of Zanthoxylum bungeanum Pericarp Improved the Hypothalamic-Pituitary-Adrenal Axis and Gut Microbiota to Attenuate Chronic Unpredictable Stress-Induced Anxiety Behavior in Rats

Mar 3, 2021Drug design, development and therapy

Zanthoxylum bungeanum oil may reduce stress-related anxiety in rats by improving stress hormone balance and gut bacteria

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Abstract

VOZB treatment (100 and 200 mg/kg/day) improved anxiety behavior in rats exposed to chronic unpredictable stress.

Treatment with VOZB increased open-arm entries and time in the elevated plus-maze test, indicating reduced anxiety.
VOZB administration decreased the protein and mRNA levels of corticotropin-releasing hormone in the hypothalamus.
The treatment elevated glucocorticoid receptor levels in the hypothalamus.
Serum hormone levels of the were reduced following VOZB treatment.
VOZB restored dysbiosis in , increasing diversity measures and altering specific bacterial families.

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BACKGROUND: Anxiety disorders (ADs) are the most prevalent mental disorders worldwide. Stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and dysbiosis of seem to contribute to the onset of ADs. This study was designed to investigate the ameliorative effect of volatile oil of(VOZB) on chronic unpredictable stress (CUS) induced anxiety behavior, as well as the altered and gut microbiota. Zanthoxylum bungeanum

METHODS: Experimental rats were exposed to the CUS for 14 consecutive days. Meanwhile, VOZB was administered at doses of 50, 100 and 200 mg/kg/day for 14 days. The anxiety behavior was evaluated by elevated plus-maze (EPM) and open field (OF). The protein expressions and mRNA levels of corticotropin-releasing hormone (CRH) and glucocorticoid receptor (GR) in hypothalamus was determined, as well the hormone levels of HPA axis in serum. Furthermore, gut microbiota was detected by16S rRNA gene sequencing. The chemical constituents of VOZB were identified by GC-MS analysis.

RESULTS: VOZB treatment (100 and 200 mg/kg/day) increased the ratio of open-arm entries and time in EPM test, as well as the central zone entries and time in OF test. Moreover, VOZB treatment reduced the protein expressions and mRNA levels of CRH, but elevated those of GR in hypothalamus. Similarly, the hormone levels of the HPA axis in serum were decreased by VOZB treatment. Besides, VOZB treatment restored the CUS-induced dysbiosis of gut microbiota, raising the Sobs and Chao indexes, inhibiting Lachnospiraceae, but facilitating Bacteroidales_S24-7_group, Lactobacillaceae, and Prevotellaceae. Additionally, Sobs and Chao indexes were negatively correlated to the serum corticosterone and CRH levels.

CONCLUSION: VOZB showed an ameliorative effect on CUS-induced anxiety behavior, potentially via inhibiting activation of the HPA axis and restoring the dysbiosis of gut microbiota, thus improving the stress-induced abnormality of the microbiota-gut-brain axis.

Key numbers

20.025

Increase in Open-Arm Entries

F-value from ANOVA for open-arm entries in EPM test

101.634

Increase in GR mRNA Levels

F-value from ANOVA for GR mRNA levels in hypothalamus

4.048

Decrease in CRH Levels

F-value from ANOVA for CRH levels in serum

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The Volatile Oil of Zanthoxylum bungeanum Pericarp Improved the Hypothalamic-Pituitary-Adrenal Axis and Gut Microbiota to Attenuate Chronic Unpredictable Stress-Induced Anxiety Behavior in Rats

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