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Volume 42 Issue 8
Aug.  2026
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Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2026  >  42(8): 793-802
Li Y,Zheng YY,Wang YH,et al.Effects of astragaloside Ⅰ on full-thickness skin defects in diabetic rats and its underlying mechanism[J].Chin J Burns Wounds,2026,42(8):793-802.DOI: 10.3760/cma.j.cn501225-20260116-00026.
Citation: Li Y,Zheng YY,Wang YH,et al.Effects of astragaloside Ⅰ on full-thickness skin defects in diabetic rats and its underlying mechanism[J].Chin J Burns Wounds,2026,42(8):793-802.DOI: 10.3760/cma.j.cn501225-20260116-00026.
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Effects of astragaloside Ⅰ on full-thickness skin defects in diabetic rats and its underlying mechanism

doi: 10.3760/cma.j.cn501225-20260116-00026

  • School of Shuren International (School of Innovation and Entrepreneurship), Shenyang Medical College, Shenyang 110034, China

Funds:

Joint Project of the Liaoning Provincial Science and Technology Program 2024011888-JH3/4700

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    Abstract
  •   Objective  To investigate the effects of astragaloside Ⅰ (AS-Ⅰ) on full-thickness skin defects in diabetic rats and its underlying mechanism.  Methods  This study was an experimental study with grouped design and repeated measures design. Twenty-four male Sprague-Dawley rats aged 6-8 weeks were divided into control group (n=6) and modeling group (n=18) using a random number table method (the same grouping method was used throughout). After successful induction of diabetes mellitus, the modeling group was further divided into model group, low-dose AS-Ⅰ group, and high-dose AS-Ⅰ group, with 6 rats in each group. A full-thickness skin defect wound of 10 mm in diameter was created on the back of each rat. Wounds in control group and model group were treated with normal saline, while wounds in low-dose AS-Ⅰ group and high-dose AS-Ⅰ group were treated with 1.15 and 11.50 mmol/L AS-Ⅰ, respectively, for 3 consecutive days. Wound healing rates of rats were calculated at 3, 5, 7, 9, 13, and 15 days after injury. At 15 days after injury, Masson's trichrome staining was used to assess the deposition of collagen fibers in wound tissue; immunohistochemical staining was performed to detect Ki-67 positive expression in wound tissue, and the expression level was quantified. Network pharmacology analysis was applied to screen for potential core targets of AS-Ⅰ in treatment of diabetic wounds; molecular docking simulation was utilized to validate the binding affinity of AS-Ⅰ to the core targets, and molecular dynamics simulation was performed to verify the dynamic stability of the interaction between AS-Ⅰ and forkhead box O1 (FOXO1). At 15 days after injury, Western blotting was used to determine the protein expression levels of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 2 (CDK2), growth factor receptor-bound protein 2 (GRB2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3), and FOXO1 in wound tissue of rats in four groups.  Results  Compared with those in control group, the wound healing rates of rats in model group at 3 and 15 days after injury were significantly decreased (P<0.05); whereas the wound healing rates of rats in low-dose AS-Ⅰ group at 7 and 13 days after injury, and in high-dose AS-Ⅰ group at 5, 7, 9, 13, and 15 days after injury were significantly increased (P<0.05). Compared with those in model group, the wound healing rates of rats in both low-dose AS-Ⅰ group and high-dose AS-Ⅰ group at 3, 9, 13, and 15 days after injury were significantly increased (P<0.05). At 15 days after injury, collagen fibers in the wound tissue of rats in control group were arranged in an orderly and dense manner; whereas those in the wound tissue of model group were sparse and disorganized; the deposition of collagen fibers in the wound tissue of rats in low-dose AS-Ⅰ group was improved compared with model group; collagen fibers in the wound tissue of rats in high-dose AS-Ⅰ group exhibited dense and orderly arrangement with a high degree of maturity. At 15 days after injury, the expression level of Ki-67 in wound tissue of rats in model group was significantly lower than that in control group (P<0.05); compared with that in model group, the Ki-67 expression level in wound tissue of rats in low-dose AS-Ⅰ group was significantly higher (P<0.05); compared with those in control group, model group, and low-dose AS-Ⅰ group, the Ki-67 expression level in wound tissue of rats in high-dose AS-Ⅰ group was significantly higher (with P values all <0.05). The results of network pharmacology analysis identified 63 overlapping targets between AS-Ⅰ-associated targets and diabetic wound-related targets, involving the FOXO signaling pathway (with target protein FOXO1) and target proteins including EGFR, CDK2, GRB2, PIK3CA, and STAT3. The results of molecular docking simulation showed that AS-Ⅰ exhibited strong binding affinity to the target proteins. The results of molecular dynamics simulation demonstrated that the conformation of the complex formed by AS-Ⅰ and FOXO1 protein could maintain dynamic stability. At 15 days after injury, compared with those in control group, the protein expression levels of STAT3, GRB2, and FOXO1 in wound tissue of rats in model group were significantly upregulated (with P values all <0.05), while the protein expression levels of PIK3CA, EGFR, and CDK2 were significantly downregulated (with P values all <0.05). Compared with those in model group, the protein expression levels of STAT3, GRB2, and FOXO1 in wound tissue of rats in low-dose AS-Ⅰ group and high-dose AS-Ⅰ group were significantly downregulated (with P values all <0.05), while the protein expression levels of PIK3CA, EGFR, and CDK2 were significantly upregulated (with P values all <0.05). Compared with those in low-dose AS-Ⅰ group, the protein expression levels of STAT3, GRB2, and FOXO1 in wound tissue of rats in high-dose AS-Ⅰ group were significantly downregulated (with P values all <0.05), while the protein expression levels of PIK3CA, EGFR, and CDK2 were significantly upregulated (with P values all <0.05).  Conclusions  AS-Ⅰ may promote wound healing of full-thickness skin defects and improve collagen fiber arrangement in diabetic rats by downregulating the protein expression of STAT3, GRB2, and FOXO1 and upregulating that of PIK3CA, EGFR, and CDK2.

     

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    • References(38)
  • [1]
    DaiY, ZhangQ, GuR, et al. Metal ion formulations for diabetic wound healing: mechanisms and therapeutic potential[J]. Int J Pharm, 2024,667(Pt A):124889. DOI: 10.1016/j.ijpharm.2024.124889.
    [2]
    马皓, 闵沛如, 章一新, 等. 辣椒素对糖尿病小鼠全层皮肤缺损的影响及其机制[J].中华烧伤与创面修复杂志,2025,41(7):645-654. DOI: 10.3760/cma.j.cn501225-20250210-00055.
    [3]
    施彦, 易亮, 张伟强, 等. 黄芩素对糖尿病小鼠全层皮肤缺损创面愈合的影响及其机制[J].中华烧伤与创面修复杂志,2024,40(11):1085-1094. DOI: 10.3760/cma.j.cn501225-20231104-00179.
    [4]
    RodriguesM, KosaricN, BonhamCA, et al. Wound healing: a cellular perspective[J]. Physiol Rev, 2019,99(1):665-706. DOI: 10.1152/physrev.00067.2017.
    [5]
    刘培, 王超, 魏绮键, 等. 过表达生长停滞特异性蛋白6的骨髓间充质干细胞对糖尿病小鼠全层皮肤缺损创面的影响及其机制[J].中华烧伤与创面修复杂志,2025,41(2):145-154. DOI: 10.3760/cma.j.cn501225-20241024-00409.
    [6]
    XueW, CaiL, TanY, et al. Cardiac-specific overexpression of HIF-1α prevents deterioration of glycolytic pathway and cardiac remodeling in streptozotocin-induced diabetic mice[J]. Am J Pathol, 2010,177(1):97-105. DOI: 10.2353/ajpath.2010.091091.
    [7]
    CarmelietP, JainRK. Molecular mechanisms and clinical applications of angiogenesis[J]. Nature, 2011, 473(7347):298-307. DOI: 10.1038/nature10144.
    [8]
    ChauhanS, GuliaM, SinghRP, et al. Diabetic wound: pathophysiology, complications and treatment strategies[J]. Curr Protein Pept Sci, 2024,25(3):200-205. DOI: 10.2174/0113892037276171231016103320.
    [9]
    HeR, LiQ, ShenW, et al. The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo[J]. Int Wound J, 2020,17(3):851-863. DOI: 10.1111/iwj.13341.
    [10]
    YangH, LvD, QuS, et al. A ROS-responsive lipid nanoparticles release multifunctional hydrogel based on microenvironment regulation promotes infected diabetic wound healing[J]. Adv Sci (Weinh), 2024,11(43):e2403219. DOI: 10.1002/advs.202403219.
    [11]
    高琼黄芪甲苷调控TGF-β1/Smad2/3通路改善高糖损伤的皮肤修复细胞的功能兰州兰州大学2023

    高琼. 黄芪甲苷调控TGF-β1/Smad2/3通路改善高糖损伤的皮肤修复细胞的功能[D]. 兰州:兰州大学, 2023.
    [12]
    费驰媛, 谢豪杰, 邢志杰, 等. 黄芪桂枝五物汤联合负压封闭引流治疗糖尿病足的疗效观察[J].中国医疗美容,2024,14(11):69-72. DOI: 10.19593/j.issn.2095-0721.2024.11.020.
    [13]
    TianY, NiY, ZhangT, et al. Potential mechanisms of Astragalus polysaccharide in diabetic wound healing: from biological functions to therapeutic applications[J]. Int J Biol Macromol, 2026,338(Pt 2):149823. DOI: 10.1016/j.ijbiomac.2025.149823.
    [14]
    LiuYX, SongXM, DanLW, et al. Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application[J]. Arch Pharm Res, 2024,47(3):165-218. DOI: 10.1007/s12272-024-01489-y.
    [15]
    黄鹏程黄芪皂苷类成分提取纯化工艺及黄芪—红花各成分在微透析探针中的回收率考察杭州浙江中医药大学2020

    黄鹏程. 黄芪皂苷类成分提取纯化工艺及黄芪—红花各成分在微透析探针中的回收率考察[D]. 杭州:浙江中医药大学, 2020.
    [16]
    ZhangX, WangJ, XiangS, et al. Astragaloside I from Astragalus attenuates diabetic kidney disease by regulating HDAC3/Klotho/TGF-β1 loop[J]. Am J Chin Med, 2024,52(6):1795-1817. DOI: 10.1142/S0192415X24500708.
    [17]
    MaJ, DongY, LiuJ, et al. The role of GRB2 in diabetes, diabetes complications and related disorders[J]. Diabetes Obes Metab, 2025,27(1):23-34. DOI: 10.1111/dom.16015.
    [18]
    LouiselleAE, NiemiecSM, ZgheibC, et al. Macrophage polarization and diabetic wound healing[J]. Transl Res, 2021,236:109-116. DOI: 10.1016/j.trsl.2021.05.006.
    [19]
    周子悦, 徐广超, 王达利. 细胞外囊泡调节免疫微环境促进糖尿病创面愈合的研究进展[J].中华烧伤与创面修复杂志,2024,40(12):1193-1198. DOI: 10.3760/cma.j.cn501225-20231215-00243.
    [20]
    ChappidiS, BuddollaV, AnkireddySR, et al. Recent trends in diabetic wound healing with nanofibrous scaffolds[J]. Eur J Pharmacol, 2023,945:175617. DOI: 10.1016/j.ejphar.2023.175617.
    [21]
    SharifiaghdamM, ShaabaniE, Faridi-MajidiR, et al. Macrophages as a therapeutic target to promote diabetic wound healing[J]. Mol Ther, 2022,30(9):2891-2908. DOI: 10.1016/j.ymthe.2022.07.016.
    [22]
    CalissiG, LamEW, LinkW. Therapeutic strategies targeting FOXO transcription factors[J]. Nat Rev Drug Discov, 2021,20(1):21-38. DOI: 10.1038/s41573-020-0088-2.
    [23]
    MiaoC, LiY, ZhangX. The functions of FoxO transcription factors in epithelial wound healing[J]. Australas J Dermatol, 2019,60(2):105-109. DOI: 10.1111/ajd.12952.
    [24]
    YadavJP, SinghAK, GrishinaM, et al. Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies[J]. Inflammopharmacology, 2024,32(1):149-228. DOI: 10.1007/s10787-023-01407-6.
    [25]
    XuF, OthmanB, LimJ, et al. Foxo1 inhibits diabetic mucosal wound healing but enhances healing of normoglycemic wounds[J]. Diabetes, 2015,64(1):243-256. DOI: 10.2337/db14-0589.
    [26]
    ZhangC, PonugotiB, TianC, et al. FOXO1 differentially regulates both normal and diabetic wound healing[J]. J Cell Biol, 2015,209(2):289-303. DOI: 10.1083/jcb.201409032.
    [27]
    CheranovSY, KarpurapuM, WangD, et al. An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis[J]. Blood, 2008,111(12):5581-5591. DOI: 10.1182/blood-2007-11-126680.
    [28]
    MuX, ChenJ, ZhuH, et al. Asiaticoside-nitric oxide synergistically accelerate diabetic wound healing by regulating key metabolites and SRC/STAT3 signaling[J/OL]. Burns Trauma, 2025,13:tkaf009[2026-01-16]. https://pubmed.ncbi.nlm.nih.gov/40066291/. DOI: 10.1093/burnst/tkaf009.
    [29]
    胡可嫣miRNA-221-3p靶向DYRK1A/STAT3调节糖尿病皮肤创面愈合的机制研究合肥安徽医科大学2023

    胡可嫣. miRNA-221-3p靶向DYRK1A/STAT3调节糖尿病皮肤创面愈合的机制研究[D].合肥:安徽医科大学, 2023.
    [30]
    ShanmugapriyaK, KimH, KangHW. EGFR-conjugated hydrogel accelerates wound healing on ulcer-induced burn wounds by targeting collagen and inflammatory cells using photoimmunomodulatory inhibition[J]. Mater Sci Eng C Mater Biol Appl, 2021,118:111541. DOI: 10.1016/j.msec.2020.111541.
    [31]
    UchiyamaA, NayakS, GrafR, et al. SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands[J]. J Invest Dermatol, 2019,139(8):1809-1820.e8. DOI: 10.1016/j.jid.2019.02.004.
    [32]
    洪旺兵长链非编码RNA XIST通过竞争性结合miR-126-3p调控EGFR促进糖尿病溃疡创面HaCat细胞增殖和迁移的机制研究南昌南昌大学2024

    洪旺兵. 长链非编码RNA XIST通过竞争性结合miR-126-3p调控EGFR促进糖尿病溃疡创面HaCat细胞增殖和迁移的机制研究[D]. 南昌:南昌大学, 2024.
    [33]
    王一硒代蛋氨酸通过PI3K/AKT通路调控炎症激活在慢性糖尿病创面治疗中的研究济南山东大学2024

    王一. 硒代蛋氨酸通过PI3K/AKT通路调控炎症激活在慢性糖尿病创面治疗中的研究[D]. 济南:山东大学, 2024.
    [34]
    MatthewsHK, BertoliC, de BruinR. Cell cycle control in cancer[J]. Nat Rev Mol Cell Biol, 2022,23(1):74-88. DOI: 10.1038/s41580-021-00404-3.
    [35]
    AltavillaD, SquadritoF, PolitoF, et al. Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice[J]. Surgery, 2011,149(2):253-261. DOI: 10.1016/j.surg.2010.04.024.
    [36]
    XiaoE, GravesDT. Impact of diabetes on the protective role of FOXO1 in wound healing[J]. J Dent Res, 2015,94(8):1025-1026. DOI: 10.1177/0022034515586353.
    [37]
    AhmadP, WangY, ZhangY, et al. Understanding exosomes in diabetic wound healing[J/OL]. Periodontol2000, 2026(2026-05-24)[2026-01-16]. https://pubmed.ncbi.nlm.nih.gov/42178716/. DOI: 10.1111/prd.70055. [published online ahead of print].
    [38]
    ZhouL, SuW, WangY, et al. FOXO1 reduces STAT3 activation and causes impaired mitochondrial quality control in diabetic cardiomyopathy[J]. Diabetes Obes Metab, 2024,26(2):732-744. DOI: 10.1111/dom.15369.
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