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Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans
Phlorizin (phloridzin) is a polyphenolic phytochemical primarily found in unripe Malus (apple). It is a glucoside of phloretin and acts as an inhibitor of renal glucose transport, thus lowering blood glucose. The objective of this study was to determine effects of dietary supplementation with phlori...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598670/ https://www.ncbi.nlm.nih.gov/pubmed/36290719 http://dx.doi.org/10.3390/antiox11101996 |
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author | Park, Suhyeon Park, Sang-Kyu |
author_facet | Park, Suhyeon Park, Sang-Kyu |
author_sort | Park, Suhyeon |
collection | PubMed |
description | Phlorizin (phloridzin) is a polyphenolic phytochemical primarily found in unripe Malus (apple). It is a glucoside of phloretin and acts as an inhibitor of renal glucose transport, thus lowering blood glucose. The objective of this study was to determine effects of dietary supplementation with phlorizin on stress response, aging, and age-related diseases using Caenorhabditis elegans as a model system. Survival after oxidative stress or ultraviolet irradiation was significantly increased by pre-treatment of phlorizin. Dietary supplementation with phlorizin also significantly extended lifespans without reducing fertility. Age-related decline of muscle function was delayed by supplementation with phlorizin. Phlorizin induced the expression of stress-responsive genes hsp-16.2 and sod-3 and nuclear localization of DAF-16, a FOXO transcription factor modulating stress response and lifespan in C. elegans. Amyloid-beta-induced toxicity was significantly reduced by phlorizin. This effect was dependent on DAF-16 and SKN-1. Increased mortality induced with a high-glucose diet was partially prevented by phlorizin via SKN-1. Inactivation of dopaminergic neurons observed in a Parkinson’s disease model was completely recovered by supplementation with phlorizin. Genetic analysis suggests that lifespan extension by phlorizin is mediated through oxidative stress response and autophagy. Taken together, these data suggest that phlorizin has strong anti-oxidant and anti-aging activities with potential to be developed as a novel anti-oxidant nutraceutical against aging and age-related diseases. |
format | Online Article Text |
id | pubmed-9598670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95986702022-10-27 Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans Park, Suhyeon Park, Sang-Kyu Antioxidants (Basel) Article Phlorizin (phloridzin) is a polyphenolic phytochemical primarily found in unripe Malus (apple). It is a glucoside of phloretin and acts as an inhibitor of renal glucose transport, thus lowering blood glucose. The objective of this study was to determine effects of dietary supplementation with phlorizin on stress response, aging, and age-related diseases using Caenorhabditis elegans as a model system. Survival after oxidative stress or ultraviolet irradiation was significantly increased by pre-treatment of phlorizin. Dietary supplementation with phlorizin also significantly extended lifespans without reducing fertility. Age-related decline of muscle function was delayed by supplementation with phlorizin. Phlorizin induced the expression of stress-responsive genes hsp-16.2 and sod-3 and nuclear localization of DAF-16, a FOXO transcription factor modulating stress response and lifespan in C. elegans. Amyloid-beta-induced toxicity was significantly reduced by phlorizin. This effect was dependent on DAF-16 and SKN-1. Increased mortality induced with a high-glucose diet was partially prevented by phlorizin via SKN-1. Inactivation of dopaminergic neurons observed in a Parkinson’s disease model was completely recovered by supplementation with phlorizin. Genetic analysis suggests that lifespan extension by phlorizin is mediated through oxidative stress response and autophagy. Taken together, these data suggest that phlorizin has strong anti-oxidant and anti-aging activities with potential to be developed as a novel anti-oxidant nutraceutical against aging and age-related diseases. MDPI 2022-10-08 /pmc/articles/PMC9598670/ /pubmed/36290719 http://dx.doi.org/10.3390/antiox11101996 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 Park, Suhyeon Park, Sang-Kyu Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title | Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title_full | Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title_fullStr | Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title_full_unstemmed | Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title_short | Anti-Oxidant and Anti-Aging Effects of Phlorizin Are Mediated by DAF-16-Induced Stress Response and Autophagy in Caenorhabditis elegans |
title_sort | anti-oxidant and anti-aging effects of phlorizin are mediated by daf-16-induced stress response and autophagy in caenorhabditis elegans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598670/ https://www.ncbi.nlm.nih.gov/pubmed/36290719 http://dx.doi.org/10.3390/antiox11101996 |
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