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
Affiliations
- Zheng-Wei Zhang
- 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
- Chun-Sheng Gao
- Beijing Institute of Pharmacology and Toxicology, Beijing 100000, China
- Heng Zhang
- Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
- Jian Yang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
- Ya-Ping Wang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
- Li-Bin Pan
- 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
- Hang Yu
- 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
- Chi-Yu He
- 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
- Hai-Bin Luo
- School of Pharmaceutical Sciences, Hainan University, Hainan 570228, China
- Zhen-Xiong Zhao
- 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
- Xin-Bo Zhou
- National Engineering Research Center for the Emergence Drugs, Beijing 100000, China
- Yu-Li Wang
- Beijing Institute of Pharmacology and Toxicology, Beijing 100000, China
- Jie Fu
- 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
- Pei Han
- 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
- Yu-Hui Dong
- Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China
- Gang Wang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China
- Song Li
- School of Pharmaceutical Sciences, Hainan University, Hainan 570228, China; Corresponding authors.
- Yan Wang
- 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; Corresponding authors.
- Jian-Dong Jiang
- 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; Corresponding authors.
- Wu Zhong
- National Engineering Research Center for the Emergence Drugs, Beijing 100000, China; Corresponding authors.
- Journal volume & issue
-
Vol. 12,
no. 8
pp. 3298 – 3312
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.
