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Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes

Glutathione (GSH) is an endogenous antioxidant found in plants, animals, fungi, and some microorganisms that protects cells by neutralizing hydrogen peroxide. Honokiol, an active ingredient of Magnolia officinalis, is known for antioxidant, anti-inflammatory, and anti-bacterial properties. We invest...

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Autores principales: Park, Eun Jung, Dusabimana, Theodomir, Je, Jihyun, Jeong, Kyuho, Yun, Seung Pil, Kim, Hye Jung, Kim, Hwajin, Park, Sang Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555803/
https://www.ncbi.nlm.nih.gov/pubmed/32942603
http://dx.doi.org/10.3390/biomedicines8090352
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author Park, Eun Jung
Dusabimana, Theodomir
Je, Jihyun
Jeong, Kyuho
Yun, Seung Pil
Kim, Hye Jung
Kim, Hwajin
Park, Sang Won
author_facet Park, Eun Jung
Dusabimana, Theodomir
Je, Jihyun
Jeong, Kyuho
Yun, Seung Pil
Kim, Hye Jung
Kim, Hwajin
Park, Sang Won
author_sort Park, Eun Jung
collection PubMed
description Glutathione (GSH) is an endogenous antioxidant found in plants, animals, fungi, and some microorganisms that protects cells by neutralizing hydrogen peroxide. Honokiol, an active ingredient of Magnolia officinalis, is known for antioxidant, anti-inflammatory, and anti-bacterial properties. We investigated the protective mechanism of honokiol through regulating cellular GSH in renal proximal tubules against acute kidney injury (AKI). First, we measured cellular GSH levels and correlated them with the expression of GSH biosynthetic enzymes after honokiol treatment in human kidney-2 (HK-2) cells. Second, we used pharmacological inhibitors or siRNA-mediated gene silencing approach to determine the signaling pathway induced by honokiol. Third, the protective effect of honokiol via de novo GSH biosynthesis was investigated in renal ischemia-reperfusion (IR) mice. Honokiol significantly increased cellular GSH levels by upregulating the subunits of glutamate-cysteine ligase (Gcl)—Gclc and Gclm. These increases were mediated by activation of nuclear factor erythroid 2-related factor 2, via PI3K/Akt and protein kinase C signaling. Consistently, honokiol treatment reduced the plasma creatinine, tubular cell death, neutrophil infiltration and lipid peroxidation in IR mice and the effect was correlated with upregulation of Gclc and Gclm. Conclusively, honokiol may benefit to patients with AKI by increasing antioxidant GSH via transcriptional activation of the biosynthetic enzymes.
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spelling pubmed-75558032020-10-19 Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes Park, Eun Jung Dusabimana, Theodomir Je, Jihyun Jeong, Kyuho Yun, Seung Pil Kim, Hye Jung Kim, Hwajin Park, Sang Won Biomedicines Article Glutathione (GSH) is an endogenous antioxidant found in plants, animals, fungi, and some microorganisms that protects cells by neutralizing hydrogen peroxide. Honokiol, an active ingredient of Magnolia officinalis, is known for antioxidant, anti-inflammatory, and anti-bacterial properties. We investigated the protective mechanism of honokiol through regulating cellular GSH in renal proximal tubules against acute kidney injury (AKI). First, we measured cellular GSH levels and correlated them with the expression of GSH biosynthetic enzymes after honokiol treatment in human kidney-2 (HK-2) cells. Second, we used pharmacological inhibitors or siRNA-mediated gene silencing approach to determine the signaling pathway induced by honokiol. Third, the protective effect of honokiol via de novo GSH biosynthesis was investigated in renal ischemia-reperfusion (IR) mice. Honokiol significantly increased cellular GSH levels by upregulating the subunits of glutamate-cysteine ligase (Gcl)—Gclc and Gclm. These increases were mediated by activation of nuclear factor erythroid 2-related factor 2, via PI3K/Akt and protein kinase C signaling. Consistently, honokiol treatment reduced the plasma creatinine, tubular cell death, neutrophil infiltration and lipid peroxidation in IR mice and the effect was correlated with upregulation of Gclc and Gclm. Conclusively, honokiol may benefit to patients with AKI by increasing antioxidant GSH via transcriptional activation of the biosynthetic enzymes. MDPI 2020-09-15 /pmc/articles/PMC7555803/ /pubmed/32942603 http://dx.doi.org/10.3390/biomedicines8090352 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Eun Jung
Dusabimana, Theodomir
Je, Jihyun
Jeong, Kyuho
Yun, Seung Pil
Kim, Hye Jung
Kim, Hwajin
Park, Sang Won
Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title_full Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title_fullStr Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title_full_unstemmed Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title_short Honokiol Protects the Kidney from Renal Ischemia and Reperfusion Injury by Upregulating the Glutathione Biosynthetic Enzymes
title_sort honokiol protects the kidney from renal ischemia and reperfusion injury by upregulating the glutathione biosynthetic enzymes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555803/
https://www.ncbi.nlm.nih.gov/pubmed/32942603
http://dx.doi.org/10.3390/biomedicines8090352
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