Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis
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). Unfortunat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00483/full |
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| author | Chun-yu Li Chun-yu Li Can Tu Can Tu Dan Gao Dan Gao Rui-lin Wang Hai-zhu Zhang Hai-zhu Zhang Ming Niu Rui-yu Li Li Cong-En Zhang Rui-sheng Li Xiao-he Xiao Mei-hua Yang Jia-Bo Wang |
| author_facet | Chun-yu Li Chun-yu Li Can Tu Can Tu Dan Gao Dan Gao Rui-lin Wang Hai-zhu Zhang Hai-zhu Zhang Ming Niu Rui-yu Li Li Cong-En Zhang Rui-sheng Li Xiao-he Xiao Mei-hua Yang Jia-Bo Wang |
| author_sort | Chun-yu Li |
| collection | DOAJ |
| description | 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 (ALT)and aspartate aminotransferase (AST) 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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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T03:03:00Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b06004d0e0d443dfafa486ff797b1fca2022-12-22T00:40:35ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-12-01710.3389/fphar.2016.00483223928Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysisChun-yu Li0Chun-yu Li1Can Tu2Can Tu3Dan Gao4Dan Gao5Rui-lin Wang6Hai-zhu Zhang7Hai-zhu Zhang8Ming Niu9Rui-yu Li Li10Cong-En Zhang11Rui-sheng Li12Xiao-he Xiao13Mei-hua Yang14Jia-Bo Wang15Chinese Academy of Medical Sciences &Peking Union Medical College302 Military Hospital of China302 Military Hospital of ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese MedicineChinese Academy of Medical Sciences &Peking Union Medical College302 Military Hospital of ChinaIntegrative Medical Center, 302 Military Hospital302 Military Hospital of ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine302 Military Hospital of China302 Military Hospital of China302 Military Hospital of ChinaResearch Center for Clinical and Translational Medicine, 302 Hospital of People’s Liberation Army302 Military Hospital of ChinaChinese Academy of Medical Sciences &Peking Union Medical College302 Military Hospital of ChinaCurrently, 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 (ALT)and aspartate aminotransferase (AST) 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.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00483/fullMetabolomicsStilbenespathway analysisPolygonum multiflorumIdiosyncratic liver injury |
| spellingShingle | Chun-yu Li Chun-yu Li Can Tu Can Tu Dan Gao Dan Gao Rui-lin Wang Hai-zhu Zhang Hai-zhu Zhang Ming Niu Rui-yu Li Li Cong-En Zhang Rui-sheng Li Xiao-he Xiao Mei-hua Yang Jia-Bo Wang Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis Frontiers in Pharmacology Metabolomics Stilbenes pathway analysis Polygonum multiflorum Idiosyncratic liver injury |
| title | Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| title_full | Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| title_fullStr | Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| title_full_unstemmed | Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| title_short | Metabolomic study on idiosyncratic liver injury induced by different extracts of Polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| title_sort | metabolomic study on idiosyncratic liver injury induced by different extracts of polygonum multiflorum in rats integrated with pattern recognition and enriched pathways analysis |
| topic | Metabolomics Stilbenes pathway analysis Polygonum multiflorum Idiosyncratic liver injury |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00483/full |
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