Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function
Background: Morphine dependence, a devastating neuropsychiatric condition, may be closely associated with gut microbiota dysbiosis. Ginsenoside Rg1 (Rg1), an active ingredient extracted from the roots of Panax ginseng C.A. Meyer, has potential health-promoting effects on the nervous system. However,...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222003249 |
| _version_ | 1811254934179414016 |
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| author | Zhijie Chen Yingbo Lin Qichun Zhou Shilin Xiao Chan Li Rukun Lin Jing Li Yifei Chen Chaohua Luo Zhixian Mo |
| author_facet | Zhijie Chen Yingbo Lin Qichun Zhou Shilin Xiao Chan Li Rukun Lin Jing Li Yifei Chen Chaohua Luo Zhixian Mo |
| author_sort | Zhijie Chen |
| collection | DOAJ |
| description | Background: Morphine dependence, a devastating neuropsychiatric condition, may be closely associated with gut microbiota dysbiosis. Ginsenoside Rg1 (Rg1), an active ingredient extracted from the roots of Panax ginseng C.A. Meyer, has potential health-promoting effects on the nervous system. However, its role in substance use disorders remains unclear. Here, we explored the potential modulatory roles of Rg1 in protection against morphine dependence. Methods: Conditioned place preference (CPP) was used for establishing a murine model of morphine dependence. 16S rRNA gene sequencing and metabolomics were performed for microbial and metabolite analysis. Molecular analysis was tested for evaluating the host serum and brain responses. Results: Rg1 prevented morphine-induced CPP in mice. The 16S rRNA gene-based microbiota analysis demonstrated that Rg1 ameliorated morphine-induced gut microbiota dysbiosis, specifically for Bacteroidetes. Moreover, Rg1 also inhibited gut microbiota-derived tryptophan metabolism and reduced the serotonin, 5-hydroxytryptamine receptor 1B (5-HTR1B), and 5-hydroxytryptamine receptor 2 A (5-HTR2A) levels. However, the Rg1-induced amelioration of CPP was not observed in mice when their gut microbiome was depleted by non-absorbable antibiotics. Subsequently, gavage with Bacteroides vulgatus increased the abundance of Bacteroidetes. B. vulgatus supplementation synergistically enhanced Rg1-alleviated morphine-induced CPP in mice with microbiome knockdown. Co-treatment with B. vulgatus and Rg1 produced suppressive effects against morphine dependency by inhibiting tryptophan metabolism and reducing the serotonin and 5-HTR1B/5-HTR2A levels. Conclusions: The gut microbiota-tryptophan metabolism-serotonin plays an important role in gut–brain signaling in morphine disorders, which may represent a novel approach for drug dependence treatment via manipulation of the gut microbial composition and tryptophan metabolite. |
| first_indexed | 2024-04-12T17:15:59Z |
| format | Article |
| id | doaj.art-774193d8ee934f83b45dd65e8d58414e |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T17:15:59Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-774193d8ee934f83b45dd65e8d58414e2022-12-22T03:23:39ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-06-01150112935Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system functionZhijie Chen0Yingbo Lin1Qichun Zhou2Shilin Xiao3Chan Li4Rukun Lin5Jing Li6Yifei Chen7Chaohua Luo8Zhixian Mo9School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China; Department of Pharmacy, Jiangmen Central Hospital, Jiangmen, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, ChinaCentral Laboratory, Southern Medical University, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China; College of Pharmacy, Guilin Medical University, Guilin, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China; Corresponding author.School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China; Department of Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Corresponding author at: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.Background: Morphine dependence, a devastating neuropsychiatric condition, may be closely associated with gut microbiota dysbiosis. Ginsenoside Rg1 (Rg1), an active ingredient extracted from the roots of Panax ginseng C.A. Meyer, has potential health-promoting effects on the nervous system. However, its role in substance use disorders remains unclear. Here, we explored the potential modulatory roles of Rg1 in protection against morphine dependence. Methods: Conditioned place preference (CPP) was used for establishing a murine model of morphine dependence. 16S rRNA gene sequencing and metabolomics were performed for microbial and metabolite analysis. Molecular analysis was tested for evaluating the host serum and brain responses. Results: Rg1 prevented morphine-induced CPP in mice. The 16S rRNA gene-based microbiota analysis demonstrated that Rg1 ameliorated morphine-induced gut microbiota dysbiosis, specifically for Bacteroidetes. Moreover, Rg1 also inhibited gut microbiota-derived tryptophan metabolism and reduced the serotonin, 5-hydroxytryptamine receptor 1B (5-HTR1B), and 5-hydroxytryptamine receptor 2 A (5-HTR2A) levels. However, the Rg1-induced amelioration of CPP was not observed in mice when their gut microbiome was depleted by non-absorbable antibiotics. Subsequently, gavage with Bacteroides vulgatus increased the abundance of Bacteroidetes. B. vulgatus supplementation synergistically enhanced Rg1-alleviated morphine-induced CPP in mice with microbiome knockdown. Co-treatment with B. vulgatus and Rg1 produced suppressive effects against morphine dependency by inhibiting tryptophan metabolism and reducing the serotonin and 5-HTR1B/5-HTR2A levels. Conclusions: The gut microbiota-tryptophan metabolism-serotonin plays an important role in gut–brain signaling in morphine disorders, which may represent a novel approach for drug dependence treatment via manipulation of the gut microbial composition and tryptophan metabolite.http://www.sciencedirect.com/science/article/pii/S0753332222003249Ginsenoside Rg1MorphineGut microbiotaTryptophan metabolism5-HTR1B/5-HTR2ASerotonin |
| spellingShingle | Zhijie Chen Yingbo Lin Qichun Zhou Shilin Xiao Chan Li Rukun Lin Jing Li Yifei Chen Chaohua Luo Zhixian Mo Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function Biomedicine & Pharmacotherapy Ginsenoside Rg1 Morphine Gut microbiota Tryptophan metabolism 5-HTR1B/5-HTR2A Serotonin |
| title | Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function |
| title_full | Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function |
| title_fullStr | Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function |
| title_full_unstemmed | Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function |
| title_short | Ginsenoside Rg1 mitigates morphine dependence via regulation of gut microbiota, tryptophan metabolism, and serotonergic system function |
| title_sort | ginsenoside rg1 mitigates morphine dependence via regulation of gut microbiota tryptophan metabolism and serotonergic system function |
| topic | Ginsenoside Rg1 Morphine Gut microbiota Tryptophan metabolism 5-HTR1B/5-HTR2A Serotonin |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222003249 |
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