Email Alerts
RSS
Volume 41 Issue 11
Nov.  2025
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2025  >  41(11): 1101-1110
Tang LJ,Fan LH,Wang JR,et al.Effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts[J].Chin J Burns Wounds,2025,41(11):1101-1110.DOI: 10.3760/cma.j.cn501225-20250109-00018.
Citation: Tang LJ,Fan LH,Wang JR,et al.Effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts[J].Chin J Burns Wounds,2025,41(11):1101-1110.DOI: 10.3760/cma.j.cn501225-20250109-00018.
shu

Effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts

doi: 10.3760/cma.j.cn501225-20250109-00018

  • Department of Spinal Cord Injury Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai 201619, China

Funds:

National Key Clinical Specialty Discipline Construction Project of China Z155080000004

Shanghai Research Center of Rehabilitation Medicine (Top Priority Research Center of Shanghai) 2023ZZ02027

More Information
    Abstract
  •   Objective  To investigate the effect and mechanism of astaxanthin on the aging of high glucose-treated human skin fibroblasts (Fbs).  Methods  The study was an experimental study. Human skin Fbs were collected and divided into control group with conventional culture, high glucose group treated with glucose at a final molarity of 30 mmol/L, and low astaxanthin group and high astaxanthin group pretreated with astaxanthin at final molarities of 25 and 50 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate was detected by the cell counting kit-8, the reactive oxygen species level in cells was detected by the fluorescent probe method, the levels of malondialdehyde, glutathione, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cells were detected by colorimetry, and the protein expression levels of p53, phosphorylated p53, p21, p16, Rb, phosphorylated Rb, matrix metalloproteinase 1 (MMP1), MMP3, and MMP13 in cells and nuclear factor-erythroid 2-related factor 2 (Nrf2) in cytoplasm and nucleus were detected by Western blotting. Another batch of human skin Fbs were collected and divided into control group, high glucose group, and high astaxanthin group which were treated as before, and high astaxanthin+ML385 group, which were pretreated with astaxanthin at a final molarity of 50 μmol/L and ML385 at a final molarity of 10 μmol/L respectively and then treated as that in high glucose group. After 48 h of culture, the cell survival rate, the protein expression levels of p53, phosphorylated p53, p21, p16, Rb, phosphorylated Rb, MMP1, MMP3, and MMP13 in cells and Nrf2 in cytoplasm and nucleus were detected as before. The sample number in all experiments above was 3.  Results  After 48 h of culture, compared with that in control group, the cell survival rate in high glucose group was significantly decreased (P<0.05); compared with that in high glucose group, the cell survival rates in low astaxanthin group and high astaxanthin group were significantly increased (P<0.05); compared with that in low astaxanthin group, the cell survival rate in high astaxanthin group was significantly increased (P<0.05). Compared with those in control group, the levels of reactive oxygen species and malondialdehyde in cells were significantly increased (P<0.05), while the levels of glutathione, SOD, CAT, and GSH-Px in cells were significantly decreased in high glucose group (P<0.05). Compared with those in high glucose group, the levels of reactive oxygen species and malondialdehyde in cells were significantly decreased (P<0.05), while the levels of CAT and GSH-Px in cells were significantly increased in low astaxanthin group (P<0.05); the levels of reactive oxygen species and malondialdehyde in cells were significantly decreased (P<0.05), while the levels of glutathione, SOD, CAT, and GSH-Px in cells were significantly increased in high astaxanthin group (P<0.05). Compared with those in low astaxanthin group, the levels of reactive oxygen species and malondialdehyde in cells were significantly decreased (P<0.05), while the levels of glutathione, CAT, and GSH-Px in cells were significantly increased in high astaxanthin group (P<0.05). Compared with those in control group, the protein expression levels of p53, p21, phosphorylated p53, p16, Rb, MMP1, MMP3, and MMP13 in cells were significantly increased (P<0.05), while the protein expression level of phosphorylated Rb in cells was significantly decreased in high glucose group (P<0.05). Compared with those in high glucose group, the protein expression levels of p53, p21, phosphorylated p53, and MMP13 in cells were significantly decreased (P<0.05), while the protein expression level of phosphorylated Rb in cells was significantly increased in low astaxanthin group (P<0.05); the protein expression levels of p53, p21, phosphorylated p53, p16, Rb, MMP1, MMP3, and MMP13 in cells were significantly decreased (P<0.05), while the protein expression level of phosphorylated Rb in cells was significantly increased in high astaxanthin group (P<0.05). Compared with those in low astaxanthin group, the protein expression levels of p21, phosphorylated p53, p16, Rb, and MMP1 in cells in high astaxanthin group were significantly decreased (P<0.05). Compared with those in control group and high astaxanthin group, the protein expression level of cytoplasmic Nrf2 was significantly increased (with P values both <0.05), while the protein expression level of nuclear Nrf2 was significantly decreased in high glucose group (with P values both <0.05). Compared with those in low astaxanthin group, the protein expression level of cytoplasmic Nrf2 was significantly increased in high glucose group (P<0.05); the protein expression level of cytoplasmic Nrf2 was significantly decreased (P<0.05), while the protein expression level of nuclear Nrf2 was significantly increased in high astaxanthin group (P<0.05). After 48 h of culture, compared with (100.0±6.0)% in control group, the cell survival rate was significantly decreased in high glucose group ((73.9±2.2)%, P<0.05); compared with that in high glucose group, the cell survival rate was significantly increased in high astaxanthin group ((93.8±1.5)%, P<0.05); compared with that in high astaxanthin group, the cell survival rate was significantly decreased in high astaxanthin+ML385 group ((71.7±2.7)%, P<0.05). Compared with those in control group and high astaxanthin group, the protein expression levels of p53, phosphorylated p53, p21, p16, Rb, MMP1, MMP3, and MMP13 in cells were significantly increased (P<0.05), while the protein expression level of phosphorylated Rb in cells was significantly decreased in high glucose group (with P values both <0.05); compared with those in high astaxanthin group, the protein expression levels of p53, phosphorylated p53, p21, p16, Rb, MMP1, and MMP13 in cells were significantly increased (P<0.05), while the protein expression level of phosphorylated Rb in cells was significantly decreased in high astaxanthin+ML385 group (P<0.05). Compared with that in control group, the protein expression level of cytoplasmic Nrf2 was significantly increased in high glucose group (P<0.05); compared with those in high glucose group, the protein expression level of cytoplasmic Nrf2 was significantly decreased (P<0.05), while the protein expression level of nuclear Nrf2 was significantly increased in high astaxanthin group (P<0.05); compared with that in high astaxanthin group, the protein expression level of nuclear Nrf2 was significantly decreased in high astaxanthin+ML385 group (P<0.05).  Conclusions  Astaxanthin can alleviate aging of high glucose-treated human skin Fbs by regulating Nrf2 nuclear translocation to inhibit oxidative stress and downregulate the expression of aging-related proteins.

     

    • FullText(HTML)
  • loading
    • References(40)
  • [1]
    TomicD, ShawJE, MaglianoDJ. The burden and risks of emerging complications of diabetes mellitus[J]. Nat Rev Endocrinol, 2022, 18(9): 525-539.DOI: 10.1038/s41574-022-00690-7.
    [2]
    李威杰,秦晓光,朱甜,等. 减重与代谢外科新进展[J]. 中华消化外科杂志,2023,22(8):958-964.DOI: 10.3760/cma.j.cn115610-20230711-00399.
    [3]
    BurgessJL, WyantWA, Abdo AbujamraB, et al. Diabetic wound-healing science[J]. Medicina (Kaunas), 2021, 57(10):1072.DOI: 10.3390/medicina57101072.
    [4]
    WolfSJ, MelvinWJ, GallagherK. Macrophage-mediated inflammation in diabetic wound repair[J]. Semin Cell Dev Biol, 2021, 119: 111-118.DOI: 10.1016/j.semcdb.2021.06.013.
    [5]
    StoneA, DonohueCM. Diabetic foot ulcers in geriatric patients[J]. Clin Geriatr Med, 2024, 40(3): 437-447.DOI: 10.1016/j.cger.2024.03.002.
    [6]
    WilkinsonHN, HardmanMJ. Wound healing: cellular mechanisms and pathological outcomes[J]. Open Biol, 2020, 10(9): 200223.DOI: 10.1098/rsob.200223.
    [7]
    DengL, DuC, SongP, et al. The role of oxidative stress and antioxidants in diabetic wound healing[J]. Oxid Med Cell Longev, 2021, 2021: 8852759.DOI: 10.1155/2021/8852759.
    [8]
    MuX, WuX, HeW, et al. Pyroptosis and inflammasomes in diabetic wound healing[J]. Front Endocrinol (Lausanne), 2022, 13: 950798.DOI: 10.3389/fendo.2022.950798.
    [9]
    NeaguM, ConstantinC, SurcelM, et al. Diabetic neuropathy: a NRF2 disease?[J]. J Diabetes, 2024, 16(9): e13524.DOI: 10.1111/1753-0407.13524.
    [10]
    ZhangDD. Thirty years of NRF2: advances and therapeutic challenges[J]. Nat Rev Drug Discov, 2025, 24(6): 421-444.DOI: 10.1038/s41573-025-01145-0.
    [11]
    郭佳,张军霞. 核转录因子红系2相关因子2在创面愈合中的作用研究进展[J]. 中华烧伤与创面修复杂志,2023,39(1): 91-95.DOI: 10.3760/cma.j.cn501225-20220531-00209.
    [12]
    UrakazeM, KobashiC, SatouY, et al. The beneficial effects of astaxanthin on glucose metabolism and modified low-density lipoprotein in healthy volunteers and subjects with prediabetes[J]. Nutrients, 2021, 13(12):4381.DOI: 10.3390/nu13124381.
    [13]
    NishidaY, BergPC, ShakersainB, et al. Astaxanthin: past, present, and future[J]. Mar Drugs, 2023, 21(10):514.DOI: 10.3390/md21100514.
    [14]
    ZhangQ, LuoC, LiZ, et al. Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity[J]. Ecotoxicol Environ Saf, 2024, 271: 115960.DOI: 10.1016/j.ecoenv.2024.115960.
    [15]
    HafezMH, El-FarAH, ElblehiSS. Astaxanthin alleviates fipronil-induced neuronal damages in male rats through modulating oxidative stress, apoptosis, and inflammatory markers[J]. Sci Rep, 2025, 15(1): 14299.DOI: 10.1038/s41598-025-95447-3.
    [16]
    ZhuY, RuanCX, WangJ, et al. High glucose inhibits the survival of HRMCs and its mechanism[J]. Eur Rev Med Pharmacol Sci, 2022, 26(16): 5683-5688.DOI: 10.26355/eurrev_202208_29502.
    [17]
    ZhangZ, QiuY, LiW, et al. Astaxanthin alleviates foam cell formation and promotes cholesterol efflux in ox-LDL-induced RAW264.7 cells via circTPP2/miR-3073b-5p/ABCA1 pathway[J]. Molecules, 2023, 28(4):1701.DOI: 10.3390/molecules28041701.
    [18]
    YangCS, GuoXS, YueYY, et al. Astaxanthin promotes the survival of adipose-derived stem cells by alleviating oxidative stress via activating the Nrf2 signaling pathway[J]. Int J Mol Sci, 2023, 24(4):3850.DOI: 10.3390/ijms24043850.
    [19]
    JuCC, LiuXX, LiuLH, et al. Epigenetic modification: a novel insight into diabetic wound healing[J]. Heliyon, 2024, 10(6): e28086.DOI: 10.1016/j.heliyon.2024.e28086.
    [20]
    WangG, YangF, ZhouW, et al. The initiation of oxidative stress and therapeutic strategies in wound healing[J]. Biomed Pharmacother, 2023, 157: 114004.DOI: 10.1016/j.biopha.2022.114004.
    [21]
    LiuY, LiuY, HeW, et al. Fibroblasts: immunomodulatory factors in refractory diabetic wound healing[J]. Front Immunol, 2022, 13: 918223.DOI: 10.3389/fimmu.2022.918223.
    [22]
    FengJ, WangJ, WangY, et al. Oxidative stress and lipid peroxidation: prospective associations between ferroptosis and delayed wound healing in diabetic ulcers[J]. Front Cell Dev Biol, 2022, 10: 898657.DOI: 10.3389/fcell.2022.898657.
    [23]
    HuangK, MiB, XiongY, et al. Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity[J/OL]. Burns Trauma, 2025, 13: tkae052[2025-08-18].https://pubmed.ncbi.nlm.nih.gov/39927093/.DOI: 10.1093/burnst/tkae052.
    [24]
    CitrinKM, ChaubeB, Fernández-HernandoC, et al. Intracellular endothelial cell metabolism in vascular function and dysfunction[J]. Trends Endocrinol Metab, 2025, 36(8): 744-755.DOI: 10.1016/j.tem.2024.11.004.
    [25]
    GasekNS, YanP, ZhuJ, et al. Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing[J]. Nat Aging, 2025, 5(1): 21-27.DOI: 10.1038/s43587-024-00755-4.
    [26]
    ZhangS, MengN, LiuS, et al. Targeting senescent HDF with the USP7 inhibitor P5091 to enhance DFU wound healing through the p53 pathway[J]. Biochem Biophys Res Commun, 2024, 722: 150149.DOI: 10.1016/j.bbrc.2024.150149.
    [27]
    SamarawickramaPN, ZhangG, ZhuE, et al. Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice[J]. Theranostics, 2024, 14(14): 5429-5442.DOI: 10.7150/thno.100991.
    [28]
    McElhinneyK, IrnatenM, O'BrienC. P53 and myofibroblast apoptosis in organ fibrosis[J]. Int J Mol Sci, 2023, 24(7):6737.DOI: 10.3390/ijms24076737.
    [29]
    MaZ, DingY, DingX, et al. PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway[J]. Cell Death Discov, 2023, 9(1): 424.DOI: 10.1038/s41420-023-01725-2.
    [30]
    QinY, WuK, ZhangZ, et al. NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling[J]. Biochim Biophys Acta Mol Basis Dis, 2022, 1868(11): 166518.DOI: 10.1016/j.bbadis.2022.166518.
    [31]
    JiangG, JiangT, ChenJ, et al. Mitochondrial dysfunction and oxidative stress in diabetic wound[J]. J Biochem Mol Toxicol, 2023, 37(7): e23407.DOI: 10.1002/jbt.23407.
    [32]
    QinY, LiuH, WuH. Cellular senescence in health, disease, and lens aging[J]. Pharmaceuticals (Basel), 2025, 18(2):244.DOI: 10.3390/ph18020244.
    [33]
    ChoiH, KangC. Living beyond restriction: LBR promotes cellular immortalization by suppressing genomic instability and senescence[J]. FEBS J, 2024, 291(10): 2091-2093.DOI: 10.1111/febs.17141.
    [34]
    Mahiny-ShahmohammadyD, HauckL, BilliaF. Defining the molecular underpinnings controlling cardiomyocyte proliferation[J]. Clin Sci (Lond), 2022, 136(12): 911-934.DOI: 10.1042/CS20211180.
    [35]
    O'ReillyS, MarkiewiczE, IdowuOC. Aging, senescence, and cutaneous wound healing-a complex relationship[J]. Front Immunol, 2024, 15: 1429716.DOI: 10.3389/fimmu.2024.1429716.
    [36]
    ÅgrenMS, LitmanT, EriksenJO, et al. Gene expression linked to reepithelialization of human skin wounds[J]. Int J Mol Sci, 2022, 23(24):15746.DOI: 10.3390/ijms232415746.
    [37]
    JacquierEF, KassisA, MarcuD, et al. Phytonutrients in the promotion of healthspan: a new perspective[J]. Front Nutr, 2024, 11: 1409339.DOI: 10.3389/fnut.2024.1409339.
    [38]
    KanwuguON, GlukharevaTV, DanilovaIG, et al. Natural antioxidants in diabetes treatment and management: prospects of astaxanthin[J]. Crit Rev Food Sci Nutr, 2022, 62(18): 5005-5028.DOI: 10.1080/10408398.2021.1881434.
    [39]
    商冠华,田春梅. Nrf2信号通路作为虾青素治疗新靶点的研究进展[J]. 国际医药卫生导报,2024,30(1): 20-24.DOI: 10.3760/cma.j.issn.1007-1245.2024.01.004.
    [40]
    LvB, XingS, WangZ, et al. NRF2 inhibitors: recent progress, future design and therapeutic potential[J]. Eur J Med Chem, 2024, 279: 116822.DOI: 10.1016/j.ejmech.2024.116822.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(5)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (60) PDF downloads(12) Cited by()
    Proportional views
    Related

    Copyright © Chinese Journal of Burns京ICP备07035254号-14

    E-mail：shaoshangzazhi@163.com

    Website：https://zhsszz.xml-journal.net/

    Supported by: Beijing Renhe Information Technology Co. Ltd    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return