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Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice
Published on: January 7, 2019
Anshen Bunao Syrup alleviates depression on CUMS rats by reducing neuroinflammation: Integral insights from
Xucong Huang1, Shikai Yan2, Fugen Li3
1Institute of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Background:
Anshen Bunao Syrup (ABS), a traditional Chinese medicinal formula, is widely used to treat neurological disorders such as insomnia, dizziness, and neurasthenia. However, its antidepressant effect and underlying mechanisms remain insufficiently characterized.
Purpose:
This study aims to comprehensively evaluate the antidepressant effect of ABS in a rat model, and to elucidate the underlying mechanism.
Methods:
Chronic unpredictable mild stress (CUMS) induced depressive rats were used to evaluate the antidepressant effect of ABS. Histopathological alterations in the hippocampus and colonic mucosa were examined using Nissl and H&E staining. Microglial activation was evaluated by Iba-1 immunohistochemical staining. Gut microbiota composition and metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Differential gene expression and pathway regulation were investigated by transcriptomics and confirmed by Western Blot (WB).
Results:
ABS significantly ameliorated depressive-like behaviors and elevated dopamine and 5-Hydroxytryptamine levels in cortical regions. Furthermore, ABS mitigated hippocampal neuronal damage, suppressed microglial overactivation and reduced oxidative stress in the cortex. 16S rRNA sequencing analysis showed that ABS exerted antidepressant effects via modulation of the "microbiota-gut-brain" axis, particularly by altering intestinal microbiota composition, enhancing gut function, and suppressing HPA axis hyperactivity. Metabolomics revealed that ABS corrected metabolic disturbances, and alleviated inflammation-related metabolic disturbances, while transcriptomics indicated regulation of the Npas4-BDNF-PI3K/AKT signaling pathway, which was further confirmed by WB.
Conclusion:
ABS significantly ameliorated depression in a CUMS rat model, primarily through coordinated regulation of gut microbiota, metabolic homeostasis, and the Npas4-BDNF-PI3K/AKT signaling pathway, providing integrative mechanistic insights into its antidepressant effects.
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