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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.690538/full |
| _version_ | 1819082206603116544 |
|---|---|
| author | Lu Zhai Xiaohao Xu Jiangzeng Liu Chenxu Jing Xinzhao Yang Daqing Zhao Daqing Zhao Rui Jiang Li-Wei Sun Li-Wei Sun |
| author_facet | Lu Zhai Xiaohao Xu Jiangzeng Liu Chenxu Jing Xinzhao Yang Daqing Zhao Daqing Zhao Rui Jiang Li-Wei Sun Li-Wei Sun |
| author_sort | Lu Zhai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T20:12:59Z |
| format | Article |
| id | doaj.art-2022429d243a47b6bfc1ab7e49ce1983 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T20:12:59Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2022429d243a47b6bfc1ab7e49ce19832022-12-21T18:51:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-06-011210.3389/fphar.2021.690538690538A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng OligosaccharidesLu Zhai0Xiaohao Xu1Jiangzeng Liu2Chenxu Jing3Xinzhao Yang4Daqing Zhao5Daqing Zhao6Rui Jiang7Li-Wei Sun8Li-Wei Sun9Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaKey Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaKey Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun University of Chinese Medicine, Changchun, ChinaDermal 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.690538/fullpanax notoginseng oligosaccharidesreplicative senescence dermal fibroblastcell cyclecell migrationCOL-I |
| spellingShingle | Lu Zhai Xiaohao Xu Jiangzeng Liu Chenxu Jing Xinzhao Yang Daqing Zhao Daqing Zhao Rui Jiang Li-Wei Sun Li-Wei Sun A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides Frontiers in Pharmacology panax notoginseng oligosaccharides replicative senescence dermal fibroblast cell cycle cell migration COL-I |
| 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 | panax notoginseng oligosaccharides replicative senescence dermal fibroblast cell cycle cell migration COL-I |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.690538/full |
| work_keys_str_mv | AT luzhai anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT xiaohaoxu anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT jiangzengliu anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT chenxujing anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT xinzhaoyang anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT daqingzhao anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT daqingzhao anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT ruijiang anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT liweisun anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT liweisun anovelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT luzhai novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT xiaohaoxu novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT jiangzengliu novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT chenxujing novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT xinzhaoyang novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT daqingzhao novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT daqingzhao novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT ruijiang novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT liweisun novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides AT liweisun novelbiochemicalstudyofantidermalfibroblastreplicativesenescencepotentialofpanaxnotoginsengoligosaccharides |