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

• Published in: Acta pharmaceutica Sinica. B Vol. 12; no. 8; pp. 3298 - 3312
• Main Authors: Zhang, Zheng-Wei, Gao, Chun-Sheng, Zhang, Heng, Yang, Jian, Wang, Ya-Ping, Pan, Li-Bin, Yu, Hang, He, Chi-Yu, Luo, Hai-Bin, Zhao, Zhen-Xiong, Zhou, Xin-Bo, Wang, Yu-Li, Fu, Jie, Han, Pei, Dong, Yu-Hui, Wang, Gang, Li, Song, Wang, Yan, Jiang, Jian-Dong, Zhong, Wu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022; Elsevier
• Subjects: 5-Hydroxytryptophan; 5-Hydroxytryptophan decarboxylase; Depression; Drug metabolism; Gut microbiota; Morinda officinalis oligosaccharides; Original; Serotonin; Tryptophan hydroxylase; Gut microbiota; Tryptophan hydroxylase; 5-Hydroxytryptophan decarboxylase; Morinda officinalis oligosaccharides; Serotonin; 5-Hydroxytryptophan; Drug metabolism; Depression
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2022.02.032

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. Up-regulating gut microbiota tryptophan hydroxylase levels and down-regulating 5-hydroxytryptophan decarboxylase activity is the molecular mechanism of action of the anti-depressant drug Morinda officinalis oligosaccharides. [Display omitted]