AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health

Environmental stimuli attack the skin daily resulting in the generation of reactive oxygen species (ROS) and inflammation. One pathway that regulates oxidative stress in skin involves Protein Phosphatase 2A (PP2A), a phosphatase which has been previously linked to Alzheimer’s Disease and aging. Oxid...

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Autores principales:	Kristen L. Huber, José R. Fernández, Corey Webb, Karl Rouzard, Jason Healy, Masanori Tamura, Jeffry B. Stock, Maxwell Stock, Eduardo Pérez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PP2A botanical extract antioxidant anti-inflammatory grape seed cosmetic Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/9e6f4ec614da4258a367a731a2c6512d
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spelling	oai:doaj.org-article:9e6f4ec614da4258a367a731a2c6512d2021-11-11T18:22:56ZAGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health10.3390/molecules262163511420-3049https://doaj.org/article/9e6f4ec614da4258a367a731a2c6512d2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6351https://doaj.org/toc/1420-3049Environmental stimuli attack the skin daily resulting in the generation of reactive oxygen species (ROS) and inflammation. One pathway that regulates oxidative stress in skin involves Protein Phosphatase 2A (PP2A), a phosphatase which has been previously linked to Alzheimer’s Disease and aging. Oxidative stress decreases PP2A methylation in normal human dermal fibroblasts (NHDFs). Thus, we hypothesize agents that increase PP2A methylation and activity will promote skin health and combat aging. To discover novel inhibitors of PP2A demethylation activity, we screened a library of 32 natural botanical extracts. We discovered Grape Seed Extract (GSE), which has previously been reported to have several benefits for skin, to be the most potent PP2A demethylating extract. Via several fractionation and extraction steps we developed a novel grape seed extract called Activated Grape Seed Extract (AGSE), which is enriched for PP2A activating flavonoids that increase potency in preventing PP2A demethylation when compared to commercial GSE. We then determined that 1% AGSE and 1% commercial GSE exhibit distinct gene expression profiles when topically applied to a 3D human skin model. To begin to characterize AGSE’s activity, we investigated its antioxidant potential and demonstrate it reduces ROS levels in NHDFs and cell-free assays equal to or better than Vitamin C and E. Moreover, AGSE shows anti-inflammatory properties, dose-dependently inhibiting UVA, UVB and chemical-induced inflammation. These results demonstrate AGSE is a novel, multi-functional extract that modulates methylation levels of PP2A and supports the hypothesis of PP2A as a master regulator for oxidative stress signaling and aging in skin.Kristen L. HuberJosé R. FernándezCorey WebbKarl RouzardJason HealyMasanori TamuraJeffry B. StockMaxwell StockEduardo PérezMDPI AGarticlePP2Abotanical extractantioxidantanti-inflammatorygrape seedcosmeticOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6351, p 6351 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PP2A botanical extract antioxidant anti-inflammatory grape seed cosmetic Organic chemistry QD241-441
spellingShingle	PP2A botanical extract antioxidant anti-inflammatory grape seed cosmetic Organic chemistry QD241-441 Kristen L. Huber José R. Fernández Corey Webb Karl Rouzard Jason Healy Masanori Tamura Jeffry B. Stock Maxwell Stock Eduardo Pérez AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
description	Environmental stimuli attack the skin daily resulting in the generation of reactive oxygen species (ROS) and inflammation. One pathway that regulates oxidative stress in skin involves Protein Phosphatase 2A (PP2A), a phosphatase which has been previously linked to Alzheimer’s Disease and aging. Oxidative stress decreases PP2A methylation in normal human dermal fibroblasts (NHDFs). Thus, we hypothesize agents that increase PP2A methylation and activity will promote skin health and combat aging. To discover novel inhibitors of PP2A demethylation activity, we screened a library of 32 natural botanical extracts. We discovered Grape Seed Extract (GSE), which has previously been reported to have several benefits for skin, to be the most potent PP2A demethylating extract. Via several fractionation and extraction steps we developed a novel grape seed extract called Activated Grape Seed Extract (AGSE), which is enriched for PP2A activating flavonoids that increase potency in preventing PP2A demethylation when compared to commercial GSE. We then determined that 1% AGSE and 1% commercial GSE exhibit distinct gene expression profiles when topically applied to a 3D human skin model. To begin to characterize AGSE’s activity, we investigated its antioxidant potential and demonstrate it reduces ROS levels in NHDFs and cell-free assays equal to or better than Vitamin C and E. Moreover, AGSE shows anti-inflammatory properties, dose-dependently inhibiting UVA, UVB and chemical-induced inflammation. These results demonstrate AGSE is a novel, multi-functional extract that modulates methylation levels of PP2A and supports the hypothesis of PP2A as a master regulator for oxidative stress signaling and aging in skin.
format	article
author	Kristen L. Huber José R. Fernández Corey Webb Karl Rouzard Jason Healy Masanori Tamura Jeffry B. Stock Maxwell Stock Eduardo Pérez
author_facet	Kristen L. Huber José R. Fernández Corey Webb Karl Rouzard Jason Healy Masanori Tamura Jeffry B. Stock Maxwell Stock Eduardo Pérez
author_sort	Kristen L. Huber
title	AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
title_short	AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
title_full	AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
title_fullStr	AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
title_full_unstemmed	AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health
title_sort	agse: a novel grape seed extract enriched for pp2a activating flavonoids that combats oxidative stress and promotes skin health
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9e6f4ec614da4258a367a731a2c6512d
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AGSE: A Novel Grape Seed Extract Enriched for PP2A Activating Flavonoids That Combats Oxidative Stress and Promotes Skin Health

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