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Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin
- Source :
- Theranostics
- Publication Year :
- 2018
- Publisher :
- Ivyspring International Publisher, 2018.
-
Abstract
- The gut microbiota is increasingly recognized to influence brain function through the gut-brain axis. Albiflorin, an antidepressant natural drug in China with a good safety profile, is difficult to absorb and cannot be detected in the brain after oral administration. Accordingly, the antidepressant mechanism of albiflorin in vivo has not been elucidated clearly. Methods: We identified benzoic acid as the characteristic metabolite of albiflorin in vivo and in vitro, then discovered the roles of gut microbiota in the conversion of albiflorin by carboxylesterase. Pharmacodynamic and pharmacokinetic studies were performed for the antidepressant activities of albiflorin in animals, and the efficacy of benzoic acid in inhibiting D-amino acid oxidase (DAAO) in brain was further investigated. Results: We validated that gut microbiota transformed albiflorin to benzoic acid, a key metabolite in the intestine that could cross the blood-brain barrier and, as an inhibitor of DAAO in the brain, improved brain function and exerted antidepressant activity in vivo. Intestinal carboxylesterase was the crucial enzyme that generated benzoic acid from albiflorin. Additionally, the regulatory effect of albiflorin on the gut microbiota composition was beneficial to alleviate depression. Conclusion: Our findings suggest a novel gut-brain dialogue through intestinal benzoic acid for the treatment of depression and reveal that the gut microbiota may play a causal role in the pathogenesis and treatment of the central nervous system disease.
- Subjects :
- 0301 basic medicine
Bridged-Ring Compounds
D-Amino-Acid Oxidase
Metabolite
Gut–brain axis
Medicine (miscellaneous)
Administration, Oral
Pharmacology
Gut flora
digestive system
albiflorin
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Carboxylesterase
In vivo
Animals
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Biotransformation
chemistry.chemical_classification
biology
gut microbiota
gut-brain axis
benzoic acid
Brain
carboxylesterase
biology.organism_classification
Antidepressive Agents
Gastrointestinal Microbiome
Metabolic pathway
030104 developmental biology
Enzyme
chemistry
depression
Antidepressant
Metabolic Networks and Pathways
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 18387640
- Volume :
- 8
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....dc41383718136b0e9c4c8b5a1c51e005