ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level
Abstract Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and imm...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202205645 |
| _version_ | 1797943365518491648 |
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| author | Ang Liu Min Zhang Yanglin Wu Chenhui Zhang Qin Zhang Xinlin Su Xu Zhu Weidong Shi Jiangyun Liu Yang Zhang Cheng Huang Zhaowei Yan Jun Lin |
| author_facet | Ang Liu Min Zhang Yanglin Wu Chenhui Zhang Qin Zhang Xinlin Su Xu Zhu Weidong Shi Jiangyun Liu Yang Zhang Cheng Huang Zhaowei Yan Jun Lin |
| author_sort | Ang Liu |
| collection | DOAJ |
| description | Abstract Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen‐induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC‐MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ‐glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production. |
| first_indexed | 2024-04-10T20:23:01Z |
| format | Article |
| id | doaj.art-517ed288dbc8435f9d9c7d79dae8d977 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-10T20:23:01Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-517ed288dbc8435f9d9c7d79dae8d9772023-01-25T13:47:49ZengWileyAdvanced Science2198-38442023-01-01103n/an/a10.1002/advs.202205645ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine LevelAng Liu0Min Zhang1Yanglin Wu2Chenhui Zhang3Qin Zhang4Xinlin Su5Xu Zhu6Weidong Shi7Jiangyun Liu8Yang Zhang9Cheng Huang10Zhaowei Yan11Jun Lin12Department of Orthopaedics Suzhou Dushu Lake Hospital Dushu Lake Hospital Affiliated to Soochow University Medical Center of Soochow University Suzhou 215125 ChinaDepartment of Pharmacy The First Affiliated Hospital of Soochow University Suzhou 215006 ChinaDepartment of Orthopaedics Suzhou Dushu Lake Hospital Dushu Lake Hospital Affiliated to Soochow University Medical Center of Soochow University Suzhou 215125 ChinaDepartment of Orthopaedics Suzhou Dushu Lake Hospital Dushu Lake Hospital Affiliated to Soochow University Medical Center of Soochow University Suzhou 215125 ChinaDepartment of Orthopaedics Suzhou Dushu Lake Hospital Dushu Lake Hospital Affiliated to Soochow University Medical Center of Soochow University Suzhou 215125 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Suzhou 215006 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Suzhou 215006 ChinaDepartment of Orthopaedics The First Affiliated Hospital of Soochow University Suzhou 215006 ChinaCollege of Pharmaceutical Sciences Soochow University Suzhou 215123 ChinaSchool of Biology and Food Engineering Changshu Institute of Technology Changshu 215500 ChinaDepartment of Orthopaedics China‐Japan Friendship Hospital Beijing 100029 ChinaDepartment of Pharmacy The First Affiliated Hospital of Soochow University Suzhou 215006 ChinaDepartment of Orthopaedics Suzhou Dushu Lake Hospital Dushu Lake Hospital Affiliated to Soochow University Medical Center of Soochow University Suzhou 215125 ChinaAbstract Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen‐induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC‐MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ‐glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production.https://doi.org/10.1002/advs.202205645γ‐glutamylcysteineAcanthopanax senticosus polysaccharidegut microbiotametabolomicsrheumatoid arthritis |
| spellingShingle | Ang Liu Min Zhang Yanglin Wu Chenhui Zhang Qin Zhang Xinlin Su Xu Zhu Weidong Shi Jiangyun Liu Yang Zhang Cheng Huang Zhaowei Yan Jun Lin ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level Advanced Science γ‐glutamylcysteine Acanthopanax senticosus polysaccharide gut microbiota metabolomics rheumatoid arthritis |
| title | ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level |
| title_full | ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level |
| title_fullStr | ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level |
| title_full_unstemmed | ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level |
| title_short | ASPS Exhibits Anti‐Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serum γ‐Glutamylcysteine Level |
| title_sort | asps exhibits anti rheumatic effects by reprogramming gut microbiota and increasing serum γ glutamylcysteine level |
| topic | γ‐glutamylcysteine Acanthopanax senticosus polysaccharide gut microbiota metabolomics rheumatoid arthritis |
| url | https://doi.org/10.1002/advs.202205645 |
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