Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis

Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galact...

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Main Authors: Shan Tang, Yun-yi Hou, Rui-yi Hu, Jun-jie Zhang, Xu-fei Gao, Ming Zhang, Zi Wang, Rui Zhang, Pin-hui Jia, Wei Li
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S175646462400104X
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author Shan Tang
Yun-yi Hou
Rui-yi Hu
Jun-jie Zhang
Xu-fei Gao
Ming Zhang
Zi Wang
Rui Zhang
Pin-hui Jia
Wei Li
author_facet Shan Tang
Yun-yi Hou
Rui-yi Hu
Jun-jie Zhang
Xu-fei Gao
Ming Zhang
Zi Wang
Rui Zhang
Pin-hui Jia
Wei Li
author_sort Shan Tang
collection DOAJ
description Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galactose-induced N2a cells subacute aging model to investigate AFG's anti-aging activity and potential mechanisms. Results indicated that AFG treatment (8 μM) significantly reduces the overexpression of aging-related proteins (p53/p21/p16) induced by D-galactose, highlighting its anti-aging efficacy. AFG concurrently diminishes ROS accumulation, lowering extracellular lactate dehydrogenase and alleviating intracellular oxidative stress. Notably, AFG suppresses the PERK/CHOP/caspase 12 pathway, reducing intracellular Ca2+ concentration and mitigating endoplasmic reticulum (ER) stress. Additionally, AFG decreases Bax and caspase 3 expression, elevates Bcl-2 and mitochondrial membrane potential, mitigating apoptosis. NAC with 4-PBA validated the results. Overall, AFG protects N2a cells from aging by reducing ER stress and apoptosis, suggesting its potential as a key substance for treating aging and neurodegenerative diseases.
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spelling doaj.art-a6197ebd18174aae82bf598a88ed88b92024-03-20T06:09:05ZengElsevierJournal of Functional Foods1756-46462024-04-01115106102Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosisShan Tang0Yun-yi Hou1Rui-yi Hu2Jun-jie Zhang3Xu-fei Gao4Ming Zhang5Zi Wang6Rui Zhang7Pin-hui Jia8Wei Li9College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, ChinaCollege of Medicine, Jilin University, Changchun 130021, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, ChinaCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Corresponding authors at: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China; Corresponding authors at: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China; Corresponding authors at: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.Argininyl-fructosyl-glucose (AFG), a distinctive non-saponin compound isolated from red ginseng (Panax ginseng. C.A. Meyer), demonstrates neuroprotective effects. However, the molecular mechanism underlying AFG's anti-aging properties remains unclear. This study established an in vitro D-galactose-induced N2a cells subacute aging model to investigate AFG's anti-aging activity and potential mechanisms. Results indicated that AFG treatment (8 μM) significantly reduces the overexpression of aging-related proteins (p53/p21/p16) induced by D-galactose, highlighting its anti-aging efficacy. AFG concurrently diminishes ROS accumulation, lowering extracellular lactate dehydrogenase and alleviating intracellular oxidative stress. Notably, AFG suppresses the PERK/CHOP/caspase 12 pathway, reducing intracellular Ca2+ concentration and mitigating endoplasmic reticulum (ER) stress. Additionally, AFG decreases Bax and caspase 3 expression, elevates Bcl-2 and mitochondrial membrane potential, mitigating apoptosis. NAC with 4-PBA validated the results. Overall, AFG protects N2a cells from aging by reducing ER stress and apoptosis, suggesting its potential as a key substance for treating aging and neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S175646462400104XArgininyl-fructosyl-glucoseGinsengD-galactose, N2a cellSenescenceEndoplasmic reticulum stressApoptosis
spellingShingle Shan Tang
Yun-yi Hou
Rui-yi Hu
Jun-jie Zhang
Xu-fei Gao
Ming Zhang
Zi Wang
Rui Zhang
Pin-hui Jia
Wei Li
Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
Journal of Functional Foods
Argininyl-fructosyl-glucose
Ginseng
D-galactose, N2a cell
Senescence
Endoplasmic reticulum stress
Apoptosis
title Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
title_full Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
title_fullStr Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
title_full_unstemmed Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
title_short Argininyl-fructosyl-glucose (AFG) antagonizes D-galactose-induced cellular senescence of neuro-2a via inhibiting endoplasmic reticulum stress and apoptosis
title_sort argininyl fructosyl glucose afg antagonizes d galactose induced cellular senescence of neuro 2a via inhibiting endoplasmic reticulum stress and apoptosis
topic Argininyl-fructosyl-glucose
Ginseng
D-galactose, N2a cell
Senescence
Endoplasmic reticulum stress
Apoptosis
url http://www.sciencedirect.com/science/article/pii/S175646462400104X
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