Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota  

作　　者：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 

机构地区：[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

出　　处：《Acta Pharmaceutica Sinica B》2022年第8期3298-3312,共15页药学学报（英文版）

基　　金：supported by Key Project of Beijing Natural Science Foundation (No.7181007,China);the CAMS Innovation Fund for Medical Sciences (CIFMS;Nos.2016-I2M-3-011,20211-I2M-007,2021-I2M-1-027,and 2021-I2M-1-028,China);National Natural Science Foundation of China (Nos.81973290 and 82173888);Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study (Z141102004414062,China)。

摘　　要：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.

关 键 词：DEPRESSION Morinda oficinalis oligosaccharides Gut microbiota Tryptophan hydroxylase 5-Hydroxytryptophan decarboxylase 5-HYDROXYTRYPTOPHAN Serotonin Drug metabolism 

分 类 号：R285[医药卫生—中药学]