Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
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| Authors: | Zheng-Wei Zhang Chun-Sheng Gao Heng Zhang Jian Yang Ya-Ping Wang Li-Bin Pan Hang Yu Chi-Yu He Hai-Bin Luo Zhen-Xiong Zhao Xin-Bo Zhou Yu-Li Wang Jie Fu Pei Han Yu-Hui Dong Gang Wang Song Li Yan Wang Jian-Dong Jiang Wu Zhong |
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| Affiliation: | 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 Institute of Pharmacology and Toxicology, Beijing 100000, China;3. Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;4. The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China;5. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China;6. School of Pharmaceutical Sciences, Hainan University, Hainan 570228, China;7. National Engineering Research Center for the Emergence Drugs, Beijing 100000, China |
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| Abstract: | Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood–brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota. |
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| Keywords: | Depression Gut microbiota Tryptophan hydroxylase 5-Hydroxytryptophan decarboxylase 5-Hydroxytryptophan Serotonin Drug metabolism |
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