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Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology
BACKGROUND: Previous evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated. METHODS: We first used network pharmacology and molecular docking to identify the core t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195913/ https://www.ncbi.nlm.nih.gov/pubmed/37215853 http://dx.doi.org/10.1016/j.heliyon.2023.e15682 |
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author | Lu, Hongmei Xie, Dengpiao Qu, Bo Li, Mingquan He, Yuhua Liu, Weijing |
author_facet | Lu, Hongmei Xie, Dengpiao Qu, Bo Li, Mingquan He, Yuhua Liu, Weijing |
author_sort | Lu, Hongmei |
collection | PubMed |
description | BACKGROUND: Previous evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated. METHODS: We first used network pharmacology and molecular docking to identify the core targets of emodin for AKI and performed a range of experiments to validate this result. Pretreatment with emodin for 7 days, the rats were treated with bilateral renal artery clipping for 45 min to identify the prevention effect. Hypoxia/reoxygenation (H/R), and vancomycin - induced renal tubular epithelial cells (HK-2 cells) were treated with emodin to explore the related molecular mechanism. RESULTS: Network pharmacology and molecular docking showed that anti-apoptosis might be the core mechanism responsible for the action of emodin on AKI; this anti-apoptotic effect appears to because by regulation p53-related signaling pathway. Our data showed that pretreatment with emodin significantly improved renal function and renal tubular injury in renal I/R model rats (P < 0.05. The prevention effect of emodin was proved to be related to anti - apoptosis of HK-2 cells, possibly by downregulating the levels of p53, cleaved-caspase-3, pro-caspase-9, and upregulated the levels of Bcl-2. The efficacy and mechanism of emodin on anti - apoptosis was also confirmed in vancomycin - induced HK-2 cells. Meanwhile, the data also showed that emodin promoted angiogenesis in I/R damaged kidneys and H/R-induced HK-2 cells, which was associated with decreasing HIF-1α levels and increasing VEGF levels. CONCLUSIONS: Our findings indicated that the preventive effect of emodin on AKI is probably attributable to anti-apoptosis response and promoting angiogenesis effect. |
format | Online Article Text |
id | pubmed-10195913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101959132023-05-20 Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology Lu, Hongmei Xie, Dengpiao Qu, Bo Li, Mingquan He, Yuhua Liu, Weijing Heliyon Research Article BACKGROUND: Previous evidence indicated that emodin has significant advantages for preventing acute kidney injury (AKI). However, the mechanisms responsible for these effects of emodin have yet to be elucidated. METHODS: We first used network pharmacology and molecular docking to identify the core targets of emodin for AKI and performed a range of experiments to validate this result. Pretreatment with emodin for 7 days, the rats were treated with bilateral renal artery clipping for 45 min to identify the prevention effect. Hypoxia/reoxygenation (H/R), and vancomycin - induced renal tubular epithelial cells (HK-2 cells) were treated with emodin to explore the related molecular mechanism. RESULTS: Network pharmacology and molecular docking showed that anti-apoptosis might be the core mechanism responsible for the action of emodin on AKI; this anti-apoptotic effect appears to because by regulation p53-related signaling pathway. Our data showed that pretreatment with emodin significantly improved renal function and renal tubular injury in renal I/R model rats (P < 0.05. The prevention effect of emodin was proved to be related to anti - apoptosis of HK-2 cells, possibly by downregulating the levels of p53, cleaved-caspase-3, pro-caspase-9, and upregulated the levels of Bcl-2. The efficacy and mechanism of emodin on anti - apoptosis was also confirmed in vancomycin - induced HK-2 cells. Meanwhile, the data also showed that emodin promoted angiogenesis in I/R damaged kidneys and H/R-induced HK-2 cells, which was associated with decreasing HIF-1α levels and increasing VEGF levels. CONCLUSIONS: Our findings indicated that the preventive effect of emodin on AKI is probably attributable to anti-apoptosis response and promoting angiogenesis effect. Elsevier 2023-04-22 /pmc/articles/PMC10195913/ /pubmed/37215853 http://dx.doi.org/10.1016/j.heliyon.2023.e15682 Text en © 2023 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Lu, Hongmei Xie, Dengpiao Qu, Bo Li, Mingquan He, Yuhua Liu, Weijing Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title | Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title_full | Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title_fullStr | Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title_full_unstemmed | Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title_short | Emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
title_sort | emodin prevents renal ischemia-reperfusion injury via suppression of p53-mediated cell apoptosis based on network pharmacology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195913/ https://www.ncbi.nlm.nih.gov/pubmed/37215853 http://dx.doi.org/10.1016/j.heliyon.2023.e15682 |
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