Metabolomics study on the toxicity of Annona squamosa by ultraperformance liquid-chromatography high-definition mass spectrometry coupled with pattern recognition approach and metabolic pathways analysis

Miao, Yunjie; Shi, Yue; Li, Fuqiang; Shan, Chenxiao; Chen, Yong; Chen, Jianwei; Li, Xiang

doi:10.1016/j.jep.2016.03.006

Cited by 17 publications

(10 citation statements)

References 27 publications

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“…The results revealed that this metabolomics can be utilized to characterize the metabolic perturbation of different extracts of Heshouwu to elucidate the toxic effects. Biomarkers, serving as early biochemical changes in drug induced hepatotoxicity, provided an opportunity to develop predictive biomarkers that could provide valuable insights about mechanisms of hepatotoxicity (Miao et al, 2016). Compared with LPS/CH and LPS/RE treated groups, 21 potential biomarkers related to liver injury, such as oxalosuccinate, succinate, creatine, and L -valine acid and so on, had been differentially expressed in LPS/EA group.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Gao

et al. 2016

Front. Pharmacol.

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Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms, using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase and aspartate aminotransferase activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu.

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Section: Discussionmentioning

confidence: 99%

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Gao

et al. 2016

Front. Pharmacol.

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“…The proposed metabolic pathway of cimifugin is shown in Figure a. As reported in the literature (Miao et al, ), prim‐ O ‐glucosylcimifugin (compound 27) and 4′‐ O ‐ β ‐ d ‐glucosyl‐5‐ O ‐methylvisamminol (compound 51), which were the two main chromones in RS extract, mainly hydrolyzed to their aglycones in vivo and further metabolized to other metabolites.…”

Section: Resultsmentioning

confidence: 99%

“…UHPLC–Q‐TOFMS, which can provide accurate mass measurements and characteristic fragment ions of compounds, has been successfully applied for in vivo metabolite identification studies (Hu et al, ; Lin et al, ). Multivariate statistical analysis, including principal component analysis (PCA) and partial least squared discriminant analysis (PLS‐DA), has been widely used to discriminate samples from diverse biological origins, statuses or qualities in metabolomics study, and to reveal differential markers between groups (Li et al, ; Miao et al, ; Tan et al, ). The signals from the absorbed constituents and metabolites of SDD could be extracted by multivariate statistical analysis without prior knowledge of the compound structures.…”

Section: Introductionmentioning

confidence: 99%

Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q‐TOFMS and multivariate statistical analysis

Zhao²,

et al. 2020

Biomedical Chromatography

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Saposhnikovia divaricata is a commonly used traditional Chinese medicine in treating various diseases such as pyrexia, rheumatism and headache. So far, there have been few reports on the metabolism of orally administered Saposhnikovia divaricate decoction (SDD), hindering further study on its bioactive components and their pharmacological characteristics. In the present study, ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry (UHPLC–Q‐TOFMS) was used coupled with principal component analysis (PCA) and partial least squared discriminant analysis (PLS‐DA) to rapidly discover and identify the metabolites of SDD. According to the result of PLS‐DA, a total of 139 ions of interest including 87 positive ions and 52 negative ions were extracted as SDD‐related xenobiotics in urine. Finally, 12 and 65 compounds were identified as absorbed parent components and metabolites of SDD, respectively. Among them, 40 new metabolites were reported for the first time. Our results suggested that hydrolysis, hydroxylation, glucuronidation and sulfation are the major metabolic pathways of chromones, while hydroxylation, hydrogenation and sulfation are the main metabolic pathways of coumarins. This study is the first to explore the absorption and metabolism of SDD using UHPLC–Q‐TOFMS, with results providing a basis for further study of its pharmacokinetics and discovery of its bioactive components.

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“…Metabolomics is commonly applied to discover potential biomarkers and biological mechanistic information by charactering the metabolic profiling of low-molecular-weight metabolites in biosamples [1]. It offers an alternative method for monitoring the biochemical changes associated with the generation and development of the influences resulting from endogenous and exogenous factors [2].…”

Section: Introductionmentioning

confidence: 99%

“…Metabolomics can be used to analyze the differences of the blood and urine metabolites of different TCM syndromes, which can make the diagnosis of TCM syndromes more scientific and quantitative, and the uncertainty of the subjective factors can be avoided. As a convenient and effective tool, metabolomics methods have been used in the evaluation of the toxicology of TCM [2,6,7].…”

Section: Introductionmentioning

confidence: 99%

Toxicity and Its Mechanism Study of Arecae semen Aqueous Extract in Wistar Rats by UPLC‐HDMS‐Based Serum Metabolomics

Jing

Han

Lin

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Arecae semen (AS) is officially recorded in Chinese Pharmacopoeia and it is known for its multiple functions, including antidepressive, antioxidant, anti-inflammatory, and cholesterol-lowering effects, which have been confirmed by modern pharmacological study. Previous study in our laboratory showed that long-term oral administration of Arecae semen aqueous extract (ASAE) at high dosage was toxic. However, the underlying toxicological mechanism of AS is not yet clear at the biochemistry level. Hypothesis. The aim of this work was to characterize the metabolome, evaluate the metabolic changes, and study the mechanisms of the toxicity induced by different treatment doses of ASAE via metabolomics. Methods. Wistar rats were administered orally two different doses of ASAE (1500 and 4500 mg/kg/d) for 30 days. The investigation was carried out to evaluate the safety of ASAE. And, the UPLC-HDMS-based serum metabolomics in conjunction with multivariate statistical techniques was applied to investigate the serum metabolite profile and potential markers of toxicity induced by different doses of ASAE. Results. Coupled with blood biochemistry and histopathology results, the significant difference in metabolic profiling was observed between 1500 and 4500 mg/kg/d dosages of ASAE-treated rats and normal rats by using pattern recognition analysis, indicating that changes in serum metabolites must have occurred. Some significant changed metabolites such as arachidonic acid, linoleic acid, stearic acid, and LPC (18 : 1) have been found and identified. These biochemical changes in serum metabolites are related to the perturbation of linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism, which may be helpful to further understand the cardiotoxicity and neurotoxicity of ASAE. Conclusion. The study shows that the metabolomic method may be a valuable tool for studying the essence of toxicity induced by traditional Chinese medicine.

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Metabolomics study on the toxicity of Annona squamosa by ultraperformance liquid-chromatography high-definition mass spectrometry coupled with pattern recognition approach and metabolic pathways analysis

Cited by 17 publications

References 27 publications

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q‐TOFMS and multivariate statistical analysis

Toxicity and Its Mechanism Study of Arecae semen Aqueous Extract in Wistar Rats by UPLC‐HDMS‐Based Serum Metabolomics

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