Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice
Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models....
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MDPI AG
2022-03-01
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Series: | Molecules |
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Online Access: | https://www.mdpi.com/1420-3049/27/6/2019 |
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author | Kiryeong Kim Jaechan Leem |
author_facet | Kiryeong Kim Jaechan Leem |
author_sort | Kiryeong Kim |
collection | DOAJ |
description | Lipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death. |
first_indexed | 2024-03-09T13:09:04Z |
format | Article |
id | doaj.art-d56c998a318241bd87332183cb374c39 |
institution | Directory Open Access Journal |
issn | 1420-3049 |
language | English |
last_indexed | 2024-03-09T13:09:04Z |
publishDate | 2022-03-01 |
publisher | MDPI AG |
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series | Molecules |
spelling | doaj.art-d56c998a318241bd87332183cb374c392023-11-30T21:44:44ZengMDPI AGMolecules1420-30492022-03-01276201910.3390/molecules27062019Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in MiceKiryeong Kim0Jaechan Leem1Department of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, KoreaDepartment of Immunology, School of Medicine, Daegu Catholic University, Daegu 42472, KoreaLipopolysaccharide (LPS) is an endotoxin that plays a crucial role in septic acute kidney injury (AKI). Hispidulin is a natural flavonoid that possesses various biological activities. Recent studies have shown that hispidulin administration alleviates various inflammatory diseases in animal models. This study aimed to investigate the renoprotective effect of hispidulin on LPS-induced AKI. Male C57BL/6 mice were administered LPS (10 mg/kg) with or without hispidulin (50 mg/kg). Hispidulin administration attenuated renal dysfunction, histological alterations, and the upregulation of neutrophil gelatinase-associated lipocalin. This flavonoid also reduced cytokine production and Toll-like receptor 4 expression, inhibited nuclear factor-κB and mitogen-activated protein kinase cascades, and alleviated immune cell infiltration. The oxidation of lipids and DNA was also inhibited by hispidulin administration. This antioxidant effect of hispidulin was associated with the downregulation of NADPH oxidase 4, the activation of catalase and superoxide dismutase activities, and the restoration of glutathione levels. Moreover, hispidulin administration attenuated tubular cell apoptosis by inhibiting caspase-3 pathway. These data suggest that hispidulin ameliorates endotoxin-induced kidney injury by suppressing inflammation, oxidative stress, and tubular cell death.https://www.mdpi.com/1420-3049/27/6/2019endotoxinsepsisacute kidney injurynatural flavonoid |
spellingShingle | Kiryeong Kim Jaechan Leem Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice Molecules endotoxin sepsis acute kidney injury natural flavonoid |
title | Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice |
title_full | Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice |
title_fullStr | Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice |
title_full_unstemmed | Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice |
title_short | Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice |
title_sort | hispidulin ameliorates endotoxin induced acute kidney injury in mice |
topic | endotoxin sepsis acute kidney injury natural flavonoid |
url | https://www.mdpi.com/1420-3049/27/6/2019 |
work_keys_str_mv | AT kiryeongkim hispidulinamelioratesendotoxininducedacutekidneyinjuryinmice AT jaechanleem hispidulinamelioratesendotoxininducedacutekidneyinjuryinmice |