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A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription

The clinical application of cisplatin, one of the most effective chemotherapeutic agents used to treat various cancers, has been limited by the risk of adverse effects, notably nephrotoxicity. Despite intensive research for decades, there are no effective approaches for alleviating cisplatin nephrot...

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Autores principales: Song, Minhyeok, Kim, Minseok, Hoang, Dang Hieu, Kovale, Lochana Mangesh, Lee, Jihyun, Kim, Youngjoo, Lee, Changhyun, Hong, Jongki, Park, Sungchul, Choe, Wonchae, Kang, Insug, Kim, Sung Soo, Ha, Joohun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737728/
https://www.ncbi.nlm.nih.gov/pubmed/36501027
http://dx.doi.org/10.3390/nu14234997
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author Song, Minhyeok
Kim, Minseok
Hoang, Dang Hieu
Kovale, Lochana Mangesh
Lee, Jihyun
Kim, Youngjoo
Lee, Changhyun
Hong, Jongki
Park, Sungchul
Choe, Wonchae
Kang, Insug
Kim, Sung Soo
Ha, Joohun
author_facet Song, Minhyeok
Kim, Minseok
Hoang, Dang Hieu
Kovale, Lochana Mangesh
Lee, Jihyun
Kim, Youngjoo
Lee, Changhyun
Hong, Jongki
Park, Sungchul
Choe, Wonchae
Kang, Insug
Kim, Sung Soo
Ha, Joohun
author_sort Song, Minhyeok
collection PubMed
description The clinical application of cisplatin, one of the most effective chemotherapeutic agents used to treat various cancers, has been limited by the risk of adverse effects, notably nephrotoxicity. Despite intensive research for decades, there are no effective approaches for alleviating cisplatin nephrotoxicity. This study aimed to investigate the protective effects and potential mechanisms of a Gynostemma pentaphyllum leaves hydrodistillate (GPHD) and its major component, damulin B, against cisplatin-induced nephrotoxicity in vitro and in vivo. A hydro-distillation method can extract large amounts of components within a short period of time using non-toxic, environmentally friendly solvent. We found that the levels of AMP-activated protein kinase α1 (AMPKα1), reactive oxygen species (ROS), and apoptosis were tightly associated with each other in HEK293 cells treated with cisplatin. We demonstrated that AMPKα1 acted as an anti-oxidant factor and that ROS generated by cisplatin suppressed the expression of AMPKα1 at the transcriptional level, thereby resulting in induction of apoptosis. Treatment with GPHD or damulin B effectively prevented cisplatin-induced apoptosis of HEK293 cells and cisplatin-induced acute kidney injury in mice by suppressing oxidative stress and maintaining AMPKα1 levels. Therefore, our study suggests that GPHD and damulin B may serve as prospective adjuvant agents against cisplatin-induced nephrotoxicity.
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spelling pubmed-97377282022-12-11 A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription Song, Minhyeok Kim, Minseok Hoang, Dang Hieu Kovale, Lochana Mangesh Lee, Jihyun Kim, Youngjoo Lee, Changhyun Hong, Jongki Park, Sungchul Choe, Wonchae Kang, Insug Kim, Sung Soo Ha, Joohun Nutrients Article The clinical application of cisplatin, one of the most effective chemotherapeutic agents used to treat various cancers, has been limited by the risk of adverse effects, notably nephrotoxicity. Despite intensive research for decades, there are no effective approaches for alleviating cisplatin nephrotoxicity. This study aimed to investigate the protective effects and potential mechanisms of a Gynostemma pentaphyllum leaves hydrodistillate (GPHD) and its major component, damulin B, against cisplatin-induced nephrotoxicity in vitro and in vivo. A hydro-distillation method can extract large amounts of components within a short period of time using non-toxic, environmentally friendly solvent. We found that the levels of AMP-activated protein kinase α1 (AMPKα1), reactive oxygen species (ROS), and apoptosis were tightly associated with each other in HEK293 cells treated with cisplatin. We demonstrated that AMPKα1 acted as an anti-oxidant factor and that ROS generated by cisplatin suppressed the expression of AMPKα1 at the transcriptional level, thereby resulting in induction of apoptosis. Treatment with GPHD or damulin B effectively prevented cisplatin-induced apoptosis of HEK293 cells and cisplatin-induced acute kidney injury in mice by suppressing oxidative stress and maintaining AMPKα1 levels. Therefore, our study suggests that GPHD and damulin B may serve as prospective adjuvant agents against cisplatin-induced nephrotoxicity. MDPI 2022-11-24 /pmc/articles/PMC9737728/ /pubmed/36501027 http://dx.doi.org/10.3390/nu14234997 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Song, Minhyeok
Kim, Minseok
Hoang, Dang Hieu
Kovale, Lochana Mangesh
Lee, Jihyun
Kim, Youngjoo
Lee, Changhyun
Hong, Jongki
Park, Sungchul
Choe, Wonchae
Kang, Insug
Kim, Sung Soo
Ha, Joohun
A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title_full A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title_fullStr A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title_full_unstemmed A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title_short A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription
title_sort hydrodistillate of gynostemma pentaphyllum and damulin b prevent cisplatin-induced nephrotoxicity in vitro and in vivo via regulation of ampkα1 transcription
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737728/
https://www.ncbi.nlm.nih.gov/pubmed/36501027
http://dx.doi.org/10.3390/nu14234997
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