Molecular mechanisms involved in drug-induced liver injury caused by urate-lowering Chinese herbs: A network pharmacology study and biology experiments
| العنوان: | Molecular mechanisms involved in drug-induced liver injury caused by urate-lowering Chinese herbs: A network pharmacology study and biology experiments |
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| المؤلفون: | Xiaomeng Zhang, Dan Zhang, Fan Li, Yi-Zhu Dong, Zhi-Jian Lin, Bing Zhang |
| المصدر: | PLoS ONE PLoS ONE, Vol 14, Iss 5, p e0216948 (2019) |
| بيانات النشر: | Public Library of Science, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteomics, Cell signaling, Interaction Networks, Traditional Chinese medicine, Pharmacology, Signal transduction, Biochemistry, chemistry.chemical_compound, Database and Informatics Methods, 0302 clinical medicine, Computational Chemistry, Medicine and Health Sciences, Hyperuricemia, Liver injury, Multidisciplinary, Eukaryota, Signaling cascades, Rutaecarpine, Plants, Molecular Docking, Chemistry, 030220 oncology & carcinogenesis, Physical Sciences, Alkaline phosphatase, Medicine, Protein Interaction Networks, Network Analysis, Research Article, Cell biology, Computer and Information Sciences, MAPK signaling cascades, Bioinformatics, Science, Herbs, Biology, Research and Analysis Methods, 03 medical and health sciences, Evodiamine, Lactate dehydrogenase, medicine, Molecular Biology, Biology and life sciences, Organisms, Traditional medicine, medicine.disease, Tetrandrine, 030104 developmental biology, chemistry, Complementary and alternative medicine |
| الوصف: | As an important part of the comprehensive treatment methods, the urate-lowering Chinese herbs could provide favorable clinical effects on hyperuricemia in its ability to invigorate spleen and remove dampness. Owing to the long-term duration, it brought up the potential adverse reactions (ADRs) and concerns about the drug-induced liver injury from these herbs. To address this problem, the bioinformatics approaches which combined the network pharmacology, computer simulation and molecular biology experiments were undertaken to elucidate the underlying drug-induced liver injury molecular mechanisms of urate-lowering Chinese herbs. Several electronic databases were searched to identify the potential liver injury compounds in published research. Then, the putative target profile of liver injury was predicted, and the interaction network was constructed based on the links between the compounds, corresponding targets and core pathways. Accordingly, the molecular docking simulation was performed to recognize the representative compounds with hepatotoxicity. Finally, the cell experiments were conducted to investigate the biochemical indicators and expression of the crucial protein that were closely associated with liver injury. In conclusion, the current research revealed that the compounds with potential liver injury including diosgenin, baicalin, saikosaponin D, tetrandrine, rutaecarpine and evodiamine from urate-lowering Chinese herbs, could lead to decline the survival rate of L-02 cell, increase the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in cell-culture medium, enhance the expression of p-p38/p38, while the p38 inhibitor could achieve the trend of regulating and controlling liver injury. These research findings bring further support to the growing evidence that the mechanism of the liver injury induced by the compounds from urate-lowering Chinese herbs may be associated with the activation of p38α. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfe6b7b0150548574e810af718143bbeTest http://europepmc.org/articles/PMC6541264Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bfe6b7b0150548574e810af718143bbe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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