The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis
BackgroundRhubarb is an important traditional Chinese medicine, and rhein is one of its most important active ingredients. Studies have found that rhein can improve ulcerative colitis by regulating gut microbes, but there are few reports on its effects on liver diseases. Therefore, this study aims t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971409/full |
| _version_ | 1811336111625076736 |
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| author | Shuhui Liu Ruiying Yin Ziwei Yang Feili Wei Jianhua Hu |
| author_facet | Shuhui Liu Ruiying Yin Ziwei Yang Feili Wei Jianhua Hu |
| author_sort | Shuhui Liu |
| collection | DOAJ |
| description | BackgroundRhubarb is an important traditional Chinese medicine, and rhein is one of its most important active ingredients. Studies have found that rhein can improve ulcerative colitis by regulating gut microbes, but there are few reports on its effects on liver diseases. Therefore, this study aims to investigate these effects and underlying mechanisms.MethodsMice were given rhein (100 mg/kg), with both a normal control group and a model group receiving the same amount of normal saline for one week. Acute liver injury was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (10 ug/kg). Samples (blood, liver, and stool) were then collected and assessed for histological lesions and used for 16S rRNA gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS) and RNA-seq analysis.ResultsThe levels of ALT and AST in the Model group were abnormal higher compared to the normal control group, and the levels of ALT and AST were significantly relieved in the rhein group. Hepatic HE staining showed that the degree of liver injury in the rhein group was lighter than that in the model group, and microbiological results showed that norank_o:Clostridia_UCG-014, Lachnoclostridium, and Roseburia were more abundant in the model group compared to the normal control group. Notably, the rhein treatment group showed reshaped disturbance of intestinal microbial community by D-GalN/LPS and these mice also had higher levels of Verrucomicrobia, Akkermansiaceae and Bacteroidetes. Additionally, There were multiple metabolites that were significantly different between the normal control group and the model group, such as L-α-amino acid, ofloxacin-N-oxide, 1-hydroxy-1,3-diphenylpropan-2-one,and L-4-hydroxyglutamate semialdehyde, but that returned to normal levels after rhein treatment. The gene expression level in the model group also changed significantly, various genes such as Cxcl2, S100a9, Tnf, Ereg, and IL-10 were up-regulated, while Mfsd2a and Bhlhe41 were down-regulated, which were recovered after rhein treatment.ConclusionOverall, our results show that rhein alleviated D-GalN/LPS-induced acute liver injury in mice. It may help modulate gut microbiota in mice, thereby changing metabolism in the intestine. Meanwhile, rhein also may help regulate genes expression level to alleviate D-GalN/LPS-induced acute liver injury. |
| first_indexed | 2024-04-13T17:33:46Z |
| format | Article |
| id | doaj.art-f223bb26c4434848a8ca4cb603f4d326 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T17:33:46Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-f223bb26c4434848a8ca4cb603f4d3262022-12-22T02:37:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.971409971409The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysisShuhui Liu0Ruiying Yin1Ziwei Yang2Feili Wei3Jianhua Hu4Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, ChinaBeijing Youan Hospital, Capital Medical University, Beijing, ChinaBackgroundRhubarb is an important traditional Chinese medicine, and rhein is one of its most important active ingredients. Studies have found that rhein can improve ulcerative colitis by regulating gut microbes, but there are few reports on its effects on liver diseases. Therefore, this study aims to investigate these effects and underlying mechanisms.MethodsMice were given rhein (100 mg/kg), with both a normal control group and a model group receiving the same amount of normal saline for one week. Acute liver injury was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (10 ug/kg). Samples (blood, liver, and stool) were then collected and assessed for histological lesions and used for 16S rRNA gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS) and RNA-seq analysis.ResultsThe levels of ALT and AST in the Model group were abnormal higher compared to the normal control group, and the levels of ALT and AST were significantly relieved in the rhein group. Hepatic HE staining showed that the degree of liver injury in the rhein group was lighter than that in the model group, and microbiological results showed that norank_o:Clostridia_UCG-014, Lachnoclostridium, and Roseburia were more abundant in the model group compared to the normal control group. Notably, the rhein treatment group showed reshaped disturbance of intestinal microbial community by D-GalN/LPS and these mice also had higher levels of Verrucomicrobia, Akkermansiaceae and Bacteroidetes. Additionally, There were multiple metabolites that were significantly different between the normal control group and the model group, such as L-α-amino acid, ofloxacin-N-oxide, 1-hydroxy-1,3-diphenylpropan-2-one,and L-4-hydroxyglutamate semialdehyde, but that returned to normal levels after rhein treatment. The gene expression level in the model group also changed significantly, various genes such as Cxcl2, S100a9, Tnf, Ereg, and IL-10 were up-regulated, while Mfsd2a and Bhlhe41 were down-regulated, which were recovered after rhein treatment.ConclusionOverall, our results show that rhein alleviated D-GalN/LPS-induced acute liver injury in mice. It may help modulate gut microbiota in mice, thereby changing metabolism in the intestine. Meanwhile, rhein also may help regulate genes expression level to alleviate D-GalN/LPS-induced acute liver injury.https://www.frontiersin.org/articles/10.3389/fimmu.2022.971409/fullrheinacute liver injurygut microbiotametabolomicstranscriptomics |
| spellingShingle | Shuhui Liu Ruiying Yin Ziwei Yang Feili Wei Jianhua Hu The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis Frontiers in Immunology rhein acute liver injury gut microbiota metabolomics transcriptomics |
| title | The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis |
| title_full | The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis |
| title_fullStr | The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis |
| title_full_unstemmed | The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis |
| title_short | The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis |
| title_sort | effects of rhein on d galn lps induced acute liver injury in mice results from gut microbiome metabolomics and host transcriptome analysis |
| topic | rhein acute liver injury gut microbiota metabolomics transcriptomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.971409/full |
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