Acta Pharmaceutica Sinica B (Aug 2022)

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

  • 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

Journal volume & issue
Vol. 12, no. 8
pp. 3298 – 3312

Abstract

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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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