Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota
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) → ser...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522000983 |
| _version_ | 1828150396770582528 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zheng-Wei Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T21:42:59Z |
| format | Article |
| id | doaj.art-550caaf00dce49ea8a24e4a2f2b15517 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-11T21:42:59Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-550caaf00dce49ea8a24e4a2f2b155172022-12-22T04:01:30ZengElsevierActa Pharmaceutica Sinica B2211-38352022-08-0112832983312Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiotaZheng-Wei Zhang0Chun-Sheng Gao1Heng Zhang2Jian Yang3Ya-Ping Wang4Li-Bin Pan5Hang Yu6Chi-Yu He7Hai-Bin Luo8Zhen-Xiong Zhao9Xin-Bo Zhou10Yu-Li Wang11Jie Fu12Pei Han13Yu-Hui Dong14Gang Wang15Song Li16Yan Wang17Jian-Dong Jiang18Wu Zhong19State 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, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100000, ChinaBeijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaThe 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, ChinaThe 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaSchool of Pharmaceutical Sciences, Hainan University, Hainan 570228, ChinaState 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, ChinaNational Engineering Research Center for the Emergence Drugs, Beijing 100000, ChinaBeijing Institute of Pharmacology and Toxicology, Beijing 100000, ChinaState 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, ChinaState 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, ChinaBeijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, ChinaThe 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, ChinaSchool of Pharmaceutical Sciences, Hainan University, Hainan 570228, China; Corresponding authors.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.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.National Engineering Research Center for the Emergence Drugs, Beijing 100000, China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2211383522000983DepressionMorinda officinalis oligosaccharidesGut microbiotaTryptophan hydroxylase5-Hydroxytryptophan decarboxylase5-Hydroxytryptophan |
| spellingShingle | 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 Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota Acta Pharmaceutica Sinica B Depression Morinda officinalis oligosaccharides Gut microbiota Tryptophan hydroxylase 5-Hydroxytryptophan decarboxylase 5-Hydroxytryptophan |
| title | Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
| title_full | Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
| title_fullStr | Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
| title_full_unstemmed | Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
| title_short | Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota |
| title_sort | morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5 hydroxytryptophan production in the gut microbiota |
| topic | Depression Morinda officinalis oligosaccharides Gut microbiota Tryptophan hydroxylase 5-Hydroxytryptophan decarboxylase 5-Hydroxytryptophan |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522000983 |
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