ISSN: 1838-7640Theranostics
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Theranostics 2018; 8(21):5945-5959. doi:10.7150/thno.28068 This issue Cite
Research Paper
Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences / Peking Union Medical College, Beijing 100050, China
2. Beijing WONNER Biotech. Co. Ltd, Beijing 100071, China
3. College of Pharmacy, The University of Illinois at Chicago, Chicago 60607, United States
*These authors made an equal contribution to this work.
Citation:
Zhao ZX, Fu J, Ma SR, Peng R, Yu JB, Cong L, Pan LB, Zhang ZG, Tian H, Che CT, Wang Y, Jiang JD. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics 2018; 8(21):5945-5959. doi:10.7150/thno.28068. https://www.thno.org/v08p5945.htm
Other stylesAbstract
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.
Keywords: gut-brain axis, albiflorin, gut microbiota, depression, benzoic acid, carboxylesterase
Citation styles
APA
Zhao, Z.X., Fu, J., Ma, S.R., Peng, R., Yu, J.B., Cong, L., Pan, L.B., Zhang, Z.G., Tian, H., Che, C.T., Wang, Y., Jiang, J.D. (2018). Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics, 8(21), 5945-5959. https://doi.org/10.7150/thno.28068.
ACS
Zhao, Z.X.; Fu, J.; Ma, S.R.; Peng, R.; Yu, J.B.; Cong, L.; Pan, L.B.; Zhang, Z.G.; Tian, H.; Che, C.T.; Wang, Y.; Jiang, J.D. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics 2018, 8 (21), 5945-5959. DOI: 10.7150/thno.28068.
NLM
Zhao ZX, Fu J, Ma SR, Peng R, Yu JB, Cong L, Pan LB, Zhang ZG, Tian H, Che CT, Wang Y, Jiang JD. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics 2018; 8(21):5945-5959. doi:10.7150/thno.28068. https://www.thno.org/v08p5945.htm
CSE
Zhao ZX, Fu J, Ma SR, Peng R, Yu JB, Cong L, Pan LB, Zhang ZG, Tian H, Che CT, Wang Y, Jiang JD. 2018. Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin. Theranostics. 8(21):5945-5959.
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