Integrated Serum and Fecal Metabolomics Study of Collagen-Induced Arthritis Rats and the Therapeutic Effects of the Zushima Tablet

Shan, Jinjun; Peng, Linxiu; Qian, Wenjuan; Xie, Ting; An, Kang; Gao, Bei; Di, Liuqing

doi:10.3389/fphar.2018.00891

Cited by 39 publications

(23 citation statements)

References 42 publications

(38 reference statements)

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“…However, the underlying mechanisms and targets are open to be explained. Our results of untargeted metabolomics combined with UPLC-MS determined not only the differentially isolated metabolites from blood serum and tissues, but also the GERA extract [10][11] . Figures 3 and 4 showed differentially isolated metabolites between three propositions of GERA, while enrichment analysis of KEGG pathways displayed the overall differential metabolites were majorly involved in iso avonoid biosynthesis and biosynthesis of unsaturated fatty acids.…”

Section: Discussionmentioning

confidence: 86%

The Anti-RA Activities of a Couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata, Explored by Untargeted Metabolomics and Network Pharmacology.

Yang¹,

Shen

et al. 2020

Preprint

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Background The couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata (GERA), is an established formula extensively used in Chinese medicine for treating rheumatoid arthritis (RA). However, the anti-RA mechanisms of GERA are still unclear. This paper aims to explore the anti-RA mechanisms of GERA by a combined strategy of untargeted metabolomics and network pharmacology. Methods Three water extracts were prepared as propotions: Gastrodia Elata compared with Radix Aconitic Lateralis (w/w): 1:1, 3:2, or 2:3. The untargeted metabolomics were executed with UPLC-MS. The metabolites were annotated and identified by Human metabolome database (HMDB) and Lipid maps database. Finally, key genes and pathways related to anti-RA activities of GERA were mined by network pharmacology. Results The untargeted metabolomics profile displayed that four differentially expressed metabolites were involved in isoflavonoid biosynthesis and biosynthesis of unsaturated fatty acids (p < 0.05). Among these differential metabolites, the essential ingredients of GERA were linoleic acid, daidzein, and daidzin. The principal targets of anti-RA activities of GERA were IL-6, TNF, VEGFA, TP53, CASP3 and PTGS2. Thirty anti-RA targets of GERA were majorly belonged to pathways response for anti-inflammation, endothelial function and apoptosis, suggesting the fundamental process of RA treatment. Conclusion The anti-RA activities of GERA were based on the inhibition of inflammation and regulation of endothelial function and apoptosis.

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Section: Discussionmentioning

confidence: 86%

The Anti-RA Activities of a Couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata, Explored by Untargeted Metabolomics and Network Pharmacology.

Yang¹,

Shen

et al. 2020

Preprint

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“…exhibited decreased numbers of inflammatory monocytes and CD11c + Ly6c + cells and reduced levels of proinflammatory monocyte chemotactic protein- (MCP-) 1 and MCP-3 [ 87 ]. In a recent metabolomic study, altered metabolites contained citric acid and l-isoleucine both in the serum and in the faeces were identified in rats with CIA compared with the control rats [ 88 ]. Jubair et al found that in the CIA model, the absence of a dominant microbiota resulted in an approximately 40% reduction in disease severity through the regulation of mucosal and systemic cytokines and autoantibodies, and gut microbial dysbiosis was associated with the mucosal Th17 immune response, stimulating mucosal lymphoid tissue-producing autoantibodies and regulating autoantibody effector functions in the preclinical phase of CIA [ 89 ].…”

Section: Gut Microbiota and Metabolites In Ramentioning

confidence: 99%

“…Qingluo Tongbi decoction (QLT) had a beneficial effect on altered bacterial genera and families (Lachnospiraceae, Eubacteriaceae, and Leuconostocaceae) in rats with adjuvant-induced arthritis (AA) and significantly decreased the expression levels of cadherin-11, IL-17 α , TLR2, and TLR4 in synovial tissues, which negatively correlated with the abundance of Staphylococcus and Candidatus_Saccharimonas [ 114 ]. The families of bacteria in the faeces and the metabolites in both the serum and faeces were altered in rats with CIA, and the Zushima tablet (ZT) restored most of these metabolites (including l-isoleucine, l-aspartic acid, pyruvic acid, cholic acid, and hypoxanthine) and bacteria (such as Coriobacteriaceae, Bacteroidaceae, and Porphyromonadaceae) [ 88 ]. The route of administration may also influence the effect of drugs mediated by the gut microbiota and their metabolites on animals with CIA.…”

Section: Targeting the Gut Microbiota For The Treatment Of Ramentioning

confidence: 99%

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

Zhao

Fan

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases caused by abnormal immune activation and immune tolerance. Immunomodulatory cells (ICs) play a critical role in the maintenance and homeostasis of normal immune function and in the pathogenesis of RA. The human gastrointestinal tract is inhabited by trillions of commensal microbiota on the mucosal surface that play a fundamental role in the induction, maintenance, and function of the host immune system. Gut microbiota dysbiosis can impact both the local and systemic immune systems and further contribute to various diseases, such as RA. The neighbouring intestinal ICs located in distinct intestinal mucosa may be the most likely intermediary by which the gut microbiota can affect the occurrence and development of RA. However, the reciprocal interaction between the components of the gut microbiota and their microbial metabolites with distinct ICs and how this interaction may impact the development of RA are not well studied. Therefore, a better understanding of the gut microbiota, ICs, and their interactions might improve our knowledge of the mechanisms by which the gut microbiota contribute to RA and facilitate the further development of novel therapeutic approaches. In this review, we have summarized the roles of the gut microbiota in the immunopathogenesis of RA, especially the interactions between the gut microbiota and ICs, and further discussed the strategies for treating RA by targeting/regulating the gut microbiota.

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“…Fecal SCFAs were quantified using gas chromatography-mass spectrometry (GC-MS) (Trace 1310-TSQ8000 Evo, Thermo, USA) following previous protocols (Shan et al, 2018;Luo et al, 2019). Briefly, gradient concentrations of acetate (ROE, USA), propionate (Dr. Ehrenstorfer, Germany), and butyrate (TCI, China) were prepared for standard curves.…”

Section: Gas Chromatography-mass Spectrometrymentioning

confidence: 99%

Gu-Ben-Fang-Xiao Decoction Ameliorated Murine Asthma in Remission Stage by Modulating Microbiota-Acetate-Tregs Axis

et al. 2020

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Dysbiosis of gut microbiota is a critical factor in the pathogenesis of asthma. Manipulating gut microbiota is a promising therapeutic intervention in asthma, and is being extensively studied. Gu-Ben-Fang-Xiao Decoction (GBFXD), derived from traditional Chinese medicine, is an effective and safe therapeutic formula for asthma in remission stage (ARS). Herein, we showed that GBFXD treatment remarkably alleviated ARS by improving respiratory function and lung histopathology. Asthmatic mice displayed a dysbiosis of gut microbiota, represented by significantly increased abundance of Bacteroidetes and decreased abundance of Firmicutes in gut, while GBFXD treatment reversed the gut dysbiosis in asthmatic mice at phylum, family, and genus levels. Moreover, our data showed that GBFXD treatment increased the abundance of short-chain fatty acid (SCFA)producing bacteria in asthmatic mice, such as Firmicutes, Lachnospiraceae, and Bifidobacteriaceae, which consequently led to elevated levels of SCFAs. Furthermore, GBFXD treatment significantly enhanced the regulatory T cell differentiation via SCFAs, particularly acetate, in asthmatic mice. More critically, the protective effect of GBFXD was shown to be transmissible among asthmatic mice through co-housing microbiota transplantation. Antibiotic cocktail and acetate replenishment experiments also further substantiated the importance of SCFA-producing gut microbiota in GBFXD action. We, thus, demonstrated for the first time that gut microbiota dysbiosis existed in ARS. GBFXD could ameliorate ARS through the microbiota-acetate-Tregs axis.

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Integrated Serum and Fecal Metabolomics Study of Collagen-Induced Arthritis Rats and the Therapeutic Effects of the Zushima Tablet

Cited by 39 publications

References 42 publications

The Anti-RA Activities of a Couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata, Explored by Untargeted Metabolomics and Network Pharmacology.

The Anti-RA Activities of a Couplet Medicinals, Gastrodia Elata and Radix Aconitic Lateralis preparata, Explored by Untargeted Metabolomics and Network Pharmacology.

Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis

Gu-Ben-Fang-Xiao Decoction Ameliorated Murine Asthma in Remission Stage by Modulating Microbiota-Acetate-Tregs Axis

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