Integrated Metabolomics and Proteomics Approach To Identify Metabolic Abnormalities in Rats with <i>Dioscorea bulbifera</i> Rhizome-Induced Hepatotoxicity

Dong-sheng, Zhao; Jiang, Li; Wang, Lingli; Wu, Zi-Tian; Li, Zhuoqing; Shi, Wei; Li, Ping; Jiang, Yan; Li, Huijun

doi:10.1021/acs.chemrestox.8b00066

Cited by 24 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Except for this discrepancy, all other results indicated the active involvement of energy metabolism in the host reaction to the S. japonicum infection. In addition, pyrimidine metabolism was reported to play important roles in DNA and RNA biosynthesis (Tian et al, 2018;Zhao et al, 2018), therefore the changes in pyrimidine metabolism we identified in this study may suggest the potential effects on DNA and RNA biosynthesis caused by S. japonicum infection in mice.…”

Section: Disturbed Metabolic Pathways Associated With S Japonicum Infectionmentioning

confidence: 73%

“…As reported in the previous study, uridine as a pyrimidine nucleoside, is the material basis of RNA synthesis, the bioavailability of which is particularly crucial to the synthesis of RNA and bio-membranes and the post-translational modification of protein (via the formation of pyrimidine nucleoside-lipid conjugates/UDP-sugar conjugates; Kurland et al, 2015 ; Cicuéndez et al, 2018 ; Tian et al, 2018 ). Uridine was also reported to exert protective effects against hepatotoxicity ( Zhao et al, 2018 ). Therefore, the reduction of uridine in our study may indicate that the DNA and RNA synthesis was disturbed in the host and liver toxicity was induced by the infection ( Zhou et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice

Huang

Zhao

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Metabolomics, as an emerging technology, has been demonstrated to be a very powerful tool in the study of the host metabolic responses to infections by parasites. Schistosomiasis is a parasitic infection caused by schistosoma worm via the direct contact with the water containing cercaria, among which Schistosoma japonicum ( S. japonicum ) is endemic in Asia. In order to characterize the schistosome-induced changes in the host metabolism and further to develop the strategy for early diagnosis of schistosomiasis, we performed comprehensive LC-MS-based metabolomics analysis of serum from mice infected by S. japonicum for 5 weeks. With the developed diagnosis strategy based on our metabolomics data, we were able to successfully detect schistosomiasis at the first week post-infection, which was 3 weeks earlier than “gold standard” methods and 2 weeks earlier than the methods based on 1 H NMR spectroscopy. Our metabolomics study revealed that S. japonicum infection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, DNA and RNA biosynthesis, phospholipid metabolism, depression of energy metabolism, glucose uptake and metabolism, and disruption of gut microbiota metabolism. In addition, we identified seventeen specific metabolites whose down-regulated profiles were closely correlated with the time-course of schistosomiasis progression and can also be used as an indicator for the worm-burdens. Interestingly, the decrease of these seventeen metabolites was particularly remarkable at the first week post-infection. Thus, our findings on mechanisms of host-parasite interaction during the disease process pave the way for the development of an early diagnosis tool and provide more insightful understandings of the potential metabolic process associated with schistosomiasis in mice. Furthermore, the diagnosis strategy developed in this work is cost-effective and is superior to other currently used diagnosis methods.

show abstract

Section: Disturbed Metabolic Pathways Associated With S Japonicum Infectionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice

Huang

Zhao

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The system was conducted with a Gersted multipurpose Sample mps2 with dual heads (Gerstel, Muehlheim, germang) and an Agilent 7890B gas chromatography. As previously described, the sample preparation procedures was executed 11,12 . Furthermore, to ensure consistently high quality of data, an extensive series of quality control (QC)/assurance procedures was employed.…”

Section: Gc-ms-based Metabolomic Analysismentioning

confidence: 99%

Integrative analysis of proteomic and metabonomics data for identification of pathways related to Rhizoma Paridis-induced hepatotoxicity

Zhao

Wang

Huang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention. Because the hepatotoxicity mechanism is little understood, this research strived to investigate the hepatotoxicity mechanism of Rhizoma Paridis extracts based on iTRAQ quantitative proteomics and metabonomics. The extraction solutions were administrated to rats for 7 days by gavage, and the hepatotoxicity was assessed through quantification of biochemical indexes and Oil red O staining. Additionally, the mechanism of hepatotoxicity was investigated by metabonomics based upon GC-MS and iTRAQ quantitative proteomics. The biochemical and histopathological analysis stood out that Rhizoma Paridis extract could induce liver injury, which was proved by the formation of fat droplets, the changes of mitochondrial structure, and biochemical parameters. The iTRAQ proteomics and metabonomics revealed that Rhizoma Paridis-induced hepatotoxicity was chiefly connected with the abnormal activity of mitochondrion function, which brought about oxidative stress injuries and inflammation, finally causing cell apoptosis. Collectively, we have provided previously uncharacterized hepatotoxic mechanism induced by Rhizoma Paridis and a reference to ensure its safe use in the future.Rhizoma Paridis, the roots of the Paris polyphylla Smith var. (Franch.), was first recorded in 'Shennong Herb' and Li Shizhen's 'Compendium of Materia' . The prepared Rhizoma Paridis has remarkable therapeutic effects on fractures, parotitis, hemostasis, snake bite, and abscess in the clinic for thousands of years. In addition, modern pharmacology indicated that Raw Rhizoma Paridis has beneficial impact on anti-tumor, immunity adjustment, analgesia, and anti-inflammation 1-3 . However, clinical researches regarding adverse reactions caused by Rhizoma Paridis and its preparations 4 , especially hepatotoxicity, have attracted significant attention in recent years 5 . The Chinese Pharmacopoeia clearly describes its hypotoxicity and reminds the patient and doctor to note the possible problems of orally ingesting Rhizoma Paridis and its drug preparations in high doses or over prolonged periods and when taken with other liver-damaging drugs. Despite these warnings, the mechanisms remained little known 6 .Recently, omic technologies are becoming important in vitro and in vivo tools for identifying potential hepatotoxicity mechanisms. The proteomics can identify the differentially expressed proteins that occur in a specific function, which may involve disease-or disorder-related changes in transcription, translation, transport, degradation, and covalent modification 7,8 . Metabolomics is another powerful technology for identifying a number of low-molecular-weight endogenous metabolites and assessing the dynamic variations in the biological samples 1

show abstract

“…The correlation network diagram established by OmicBean software (a web-based software application for interacting multi-omic data and available from http://www.omicsbean.cn/) can display moxibustion-intervened differentially expressed metabolites, DEPs, and signi cantly perturbed signaling pathways through visual interaction. The protein-metabolite interaction network was generated with a score of ≥ 2, number of nodes>60 and p-value < 0.05 [44]. Finally, the hierarchical cluster analysis of identi ed proteins and metabolites was employed by MEV software (version 4.9.0).…”

Section: Integrated Analysis Of Metabolomics and Proteomicsmentioning

confidence: 99%

Multi-omics Analysis at Serum Proteomic and Metabolomic Levels Reveals Mechanisms of Moxibustion for a Mouse Model of Ankylosing Spondylitis

Liu

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Moxibustion is widely used in ameliorating symptoms of ankylosing spondylitis (AS). The aim of this study was to identify the potential molecular profiles of moxibustion on relieving AS mice through incorporating ultra-high-performance liquid chromatography quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS) based metabolomics approach and data independent acquisition-mass spectrometry (DIA-MS) based proteomic. Methods: In this research, mice with proteoglycan-induced spondylitis (PGISp) were intervened with moxibustion for four weeks at specific acupuncture points or at non-acupuncture points. Arthritis severity, histopathological examinations, cytokines and osteoblast (OB) related genes were assessed. Protein profiling and metabolite profiling of serum of mice were examined by UHPLC-Q-TOF/MS based metabolomics technology and DIA-MS based proteomic approach. A multi-omic analysis was implemented for integrating the results of the single proteomic and metabolomic. The levels of some novel proteins in significantly enriched integrated pathways were validated by the enzyme-linked immunosorbent assay (ELISA) method. Results: Our findings clearly indicate that acupuncture points’ moxibustion can significantly decrease the arthritis index (AI) score, improve the histopathological examination and reduce the serum levels of C-reactive protein (CRP), Interferon-γ (IFN-γ), Interleukin-17 (IL-17), Alkaline phosphatase (ALP) and Osteocalcin (OCN) for AS mice. A total of 21 differentially expressed metabolites and 21 differentially expressed proteins (DEPs) were identified as potential moxibustion-intervened biomarkers for AS mice. These molecules were mainly involved in six integrative canonical pathways: mineral absorption, lipid metabolism, purine metabolism, glycolysis/gluconeogenesis, glycine, serine and threonine metabolism and phenylalanine metabolism pathways. Furthermore, The ELISA analysis of four key proteins was consistent with the results of the proteomic analysis. Conclusions: Combing UHPLC-Q-TOF/MS based metabolomics approach and DIA-MS based proteomic, as a promising tool, can advance our understanding of potential mechanisms of action of moxibustion for AS from a holistic perspective.

show abstract

Integrated Metabolomics and Proteomics Approach To Identify Metabolic Abnormalities in Rats with Dioscorea bulbifera Rhizome-Induced Hepatotoxicity

Cited by 24 publications

References 30 publications

UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice

UHPLC-MS-Based Metabolomics Analysis Reveals the Process of Schistosomiasis in Mice

Integrative analysis of proteomic and metabonomics data for identification of pathways related to Rhizoma Paridis-induced hepatotoxicity

Multi-omics Analysis at Serum Proteomic and Metabolomic Levels Reveals Mechanisms of Moxibustion for a Mouse Model of Ankylosing Spondylitis

Contact Info

Product

Resources

About