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Gut-brain Axis Metabolic Pathway Regulates Antidepressant Efficacy of Albiflorin

Gut-brain Axis Metabolic Pathway Regulates Antidepressant Efficacy of Albiflorin

Zhen-Xiong Zhao, Jie Fu, Shu-Rong Ma, Ran Peng, Jin-Bo Yu, Lin Cong, Li-Bin Pan, Zuo-Guang Zhang, Hui Tian, Chun-Tao Che, Yan Wang, Jian-Dong Jiang

Theranostics. 2018 Nov 13;8(21):5945-5959.

PMID: 30613273

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP39011900	Albiflorin		39011-90-0	Price

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