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A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides

Dermal fibroblast replicative senescence that often occurs in aging skin is characterized by loss of cell proliferative capacity, cell cycle arrest, decreased cell elongation, and decreased synthesis of dermal extracellular matrix (ECM) components. Although Panax notoginseng is known for its effecti...

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Autores principales: Zhai, Lu, Xu, Xiaohao, Liu, Jiangzeng, Jing, Chenxu, Yang, Xinzhao, Zhao, Daqing, Jiang, Rui, Sun, Li-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277921/
https://www.ncbi.nlm.nih.gov/pubmed/34276377
http://dx.doi.org/10.3389/fphar.2021.690538
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author Zhai, Lu
Xu, Xiaohao
Liu, Jiangzeng
Jing, Chenxu
Yang, Xinzhao
Zhao, Daqing
Jiang, Rui
Sun, Li-Wei
author_facet Zhai, Lu
Xu, Xiaohao
Liu, Jiangzeng
Jing, Chenxu
Yang, Xinzhao
Zhao, Daqing
Jiang, Rui
Sun, Li-Wei
author_sort Zhai, Lu
collection PubMed
description Dermal fibroblast replicative senescence that often occurs in aging skin is characterized by loss of cell proliferative capacity, cell cycle arrest, decreased cell elongation, and decreased synthesis of dermal extracellular matrix (ECM) components. Although Panax notoginseng is known for its effectiveness in alleviating many age-related degenerative diseases, few studies have evaluated P. notoginseng components for efficacy or mechanisms of action in delaying cell replicative senescence. In this study, P. notoginseng oligosaccharides (PNO) were isolated using a stepwise purification procedure involving water extraction and alcohol precipitation followed by DEAE Sepharose Fast Flow column chromatography, preparative high performance liquid chromatography, and size-exclusion chromatography. Monosaccharides detected in PNO constituents included mannose, galactose, and sorbitose in relative molar proportions of 14.2:12.3:1, respectively, aligning with PNO absorption spectrum results resembling typical known spectra for sugars. In vitro, PNO treatment of replicative senescent NIH-3T3 fibroblasts significantly promoted cell vitality, inhibited SA-β-galactosidase (SA-β-Gal) activity, and reduced p16 and p21 protein-level expression. Moreover, PNO treatment of senescent fibroblasts led to a lower proportion of G1 phase cells and higher proportion of S phase cells, while also inducing aging NIH-3T3 cells to migrate and synthesize collagen-I (CoL-I). Mechanistically, PNO treatment up-regulated expression of proliferating cell nuclear antigen (PCNA), cyclin E, cyclin D1, and cyclin-dependent kinase 4 (CDK4) proteins and promoted phosphorylation of MEK, p38, and ERK1/2 to trigger cell cycle progression. Additionally, PNO treatment also up-regulated protein-level expression of TGF-β1 and levels of p-Smad2/3, p-FAK, and p-Pax to trigger CoL-I synthesis and cell migration. Taken together, these findings demonstrate that oligosaccharides purified from P. notoginseng could reverse fibroblast replicative senescence by promoting fibroblast cell proliferation, migration, and CoL-I production.
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spelling pubmed-82779212021-07-15 A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides Zhai, Lu Xu, Xiaohao Liu, Jiangzeng Jing, Chenxu Yang, Xinzhao Zhao, Daqing Jiang, Rui Sun, Li-Wei Front Pharmacol Pharmacology Dermal fibroblast replicative senescence that often occurs in aging skin is characterized by loss of cell proliferative capacity, cell cycle arrest, decreased cell elongation, and decreased synthesis of dermal extracellular matrix (ECM) components. Although Panax notoginseng is known for its effectiveness in alleviating many age-related degenerative diseases, few studies have evaluated P. notoginseng components for efficacy or mechanisms of action in delaying cell replicative senescence. In this study, P. notoginseng oligosaccharides (PNO) were isolated using a stepwise purification procedure involving water extraction and alcohol precipitation followed by DEAE Sepharose Fast Flow column chromatography, preparative high performance liquid chromatography, and size-exclusion chromatography. Monosaccharides detected in PNO constituents included mannose, galactose, and sorbitose in relative molar proportions of 14.2:12.3:1, respectively, aligning with PNO absorption spectrum results resembling typical known spectra for sugars. In vitro, PNO treatment of replicative senescent NIH-3T3 fibroblasts significantly promoted cell vitality, inhibited SA-β-galactosidase (SA-β-Gal) activity, and reduced p16 and p21 protein-level expression. Moreover, PNO treatment of senescent fibroblasts led to a lower proportion of G1 phase cells and higher proportion of S phase cells, while also inducing aging NIH-3T3 cells to migrate and synthesize collagen-I (CoL-I). Mechanistically, PNO treatment up-regulated expression of proliferating cell nuclear antigen (PCNA), cyclin E, cyclin D1, and cyclin-dependent kinase 4 (CDK4) proteins and promoted phosphorylation of MEK, p38, and ERK1/2 to trigger cell cycle progression. Additionally, PNO treatment also up-regulated protein-level expression of TGF-β1 and levels of p-Smad2/3, p-FAK, and p-Pax to trigger CoL-I synthesis and cell migration. Taken together, these findings demonstrate that oligosaccharides purified from P. notoginseng could reverse fibroblast replicative senescence by promoting fibroblast cell proliferation, migration, and CoL-I production. Frontiers Media S.A. 2021-06-30 /pmc/articles/PMC8277921/ /pubmed/34276377 http://dx.doi.org/10.3389/fphar.2021.690538 Text en Copyright © 2021 Zhai, Xu, Liu, Jing, Yang, Zhao, Jiang and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhai, Lu
Xu, Xiaohao
Liu, Jiangzeng
Jing, Chenxu
Yang, Xinzhao
Zhao, Daqing
Jiang, Rui
Sun, Li-Wei
A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title_full A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title_fullStr A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title_full_unstemmed A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title_short A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides
title_sort novel biochemical study of anti-dermal fibroblast replicative senescence potential of panax notoginseng oligosaccharides
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277921/
https://www.ncbi.nlm.nih.gov/pubmed/34276377
http://dx.doi.org/10.3389/fphar.2021.690538
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