Shugan granule contributes to the improvement of depression-like behaviors in chronic restraint stress-stimulated rats by altering gut microbiota.

Abstract

AIM:

The investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS).

METHODS:

The fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1 mg/kg/day). Depressive behaviors of these rats were determined through an open-field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS-stimulated microglia and CRS-stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor.

RESULTS:

(i) SGKL improved the altered behaviors in CRS-stimulated rats; (ii) SGKL ameliorated the CRS-induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF-α, IL-1β, and IL-6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α-diversity indices and shifted β-diversity in CRS-stimulated rats; (v) at the genus level, SGKL decreased the CRS-enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL-treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS-decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS-induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats.

CONCLUSION:

SGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.

• Authors: Junnan Li, Yannan Li, Wenzhe Duan, Zhonghui Zhao, Lixuan Yang, Wei Wei, Jingchun Li, Yang Li, Yao Yu, Baoan Dai, Rongjuan Guo
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 28 Issue 9 Pg. 1409-1424 (09 2022) ISSN: 1755-5949 [Electronic] England
• PMID: 35713215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Chemical References

• Drugs, Chinese Herbal
• Lipopolysaccharides
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Chronic Disease
• Depression (drug therapy, etiology, metabolism)
• Drugs, Chinese Herbal (pharmacology)
• Gastrointestinal Microbiome (drug effects)
• Inflammation (drug therapy)
• Lipopolysaccharides (toxicity)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Restraint, Physical (adverse effects)
• Stress, Psychological (drug therapy, etiology, metabolism)
• TOR Serine-Threonine Kinases (metabolism)