Email Alerts
RSS
Volume 41 Issue 7
Jul.  2025
Turn off MathJax
Article Contents
Article Navigation >  CHINESE JOURNAL OF BURNS AND WOUNDS  > 2025  >  41(7): 645-654
Ma Hao, Min Peiru, Zhang Yixin, et al. Effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2025, 41(7): 645-654. Doi: 10.3760/cma.j.cn501225-20250210-00055
Citation: Ma Hao, Min Peiru, Zhang Yixin, et al. Effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice[J]. CHINESE JOURNAL OF BURNS AND WOUNDS, 2025, 41(7): 645-654. Doi: 10.3760/cma.j.cn501225-20250210-00055
shu

Effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice

doi: 10.3760/cma.j.cn501225-20250210-00055

  • Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Funds:

General Program of National Natural Science Foundation of China 82372527

Youth Science Fund Project of National Natural Science Foundation of China 82302806

Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality 22MC1940300

More Information
    Abstract
  •   Objective  To investigate the effects and mechanisms of capsaicin on full-thickness skin defects in diabetic mice.  Methods  This study was an experimental study. Thirty-six male db/db mice aged 6-8 weeks were taken. Circular full-thickness skin defect wounds (6 mm in diameter) were created on their backs. According to the random number table method (grouping method same below), the mice were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group injected with normal saline, 10 μmol/L capsaicin solution, and 20 μmol/L capsaicin solution, respectively (n=12). Immediately after modeling and on day 2, 30 μL of the corresponding solution was injected locally into the wounds. At 4, 8, and 12 days after injury, wound healing status was observed grossly and the percentage of residual wound area was calculated. At 12 days after injury, the proportions of inflammatory cell, collagen fiber, and CD31-positive expression areas in the wound of mice were observed and detected respectively using hematoxylin and eosin staining, Masson staining, and immunohistochemical staining, and the protein expression of transient receptor potential vanilloid type 1 (TRPV1) in the wound tissue of mice was detected using Western blotting. Human primary fibroblasts were prepared from normal skin tissue obtained from 5 patients (2 male and 3 female patients, aged 20-45 years) who were admitted to the Department of Plastic and Reconstructive Surgery of Shanghai Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine in October 2024. Cells in the logarithmic growth phase (passages 2-5) were used for subsequent experiments. Cells were divided into control group and high-concentration capsaicin group, cultured in complete media without or with 20 μmol/L capsaicin, respectively. After 24 hours of culture, differentially expressed genes (DEGs) between two groups were identified using the DESeq2 R package, followed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The cells were divided into control group, low-concentration capsaicin group, and high-concentration capsaicin group, which were cultured in complete media without capsaicin, and with 10 μmol/L capsaicin, and with 20 μmol/L capsaicin, respectively. After 48 hours of culture, cell apoptosis status was assessed using flow cytometer. The protein expression levels of protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in cells were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. At 12 days after injury, the protein expression levels of Akt, p-Akt, mTOR, and p-mTOR in the wounds of diabetic mice in both control group and high-concentration capsaicin group were detected by Western blotting, and the p-Akt/Akt and p-mTOR/mTOR ratios were calculated. All animal experiments used a sample size of 6, and all cellular experiments used 3.  Results  At 4 days after injury, the wounds of three groups of diabetic mice began to heal gradually, and the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.31 and 2.87, respectively, P < 0.05). At 8 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 2.55 and 5.38, respectively, P < 0.05). At 12 days after injury, the percentages of residual wound area of mice in both low-concentration capsaicin group and high-concentration capsaicin group remained significantly lower than that in control group (with t values of 3.31 and 6.24, respectively, P < 0.05), with the high-concentration capsaicin group showing a significantly greater reduction compared to that in low-concentration capsaicin group (t=3.42, P < 0.05). At 12 days after injury, the proportion of inflammatory cell area in the wound of mice in high-concentration capsaicin group was (6.2±1.8)%, significantly lower than (15.5±3.0)% in control group (t=6.45, P < 0.05). The proportion of collagen fiber area, proportion of CD31-positive expression area, and protein expression of TRPV1 in the wound of mice in high-concentration capsaicin group were significantly higher compared with those in control group (with t values of 5.48, 7.11, and 15.41, respectively, P < 0.05). After 24 hours of culture, 51 DEGs with significantly differential expression were detected in high-concentration capsaicin group of cells compared with those in control group (P < 0.05), with 31 upregulated and 20 downregulated genes. GO analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in biological processes such as extracellular matrix (ECM) polymerization, extracellular structure organization, collagen metabolic process regulation, and ECM component secretion regulation. KEGG analysis showed that the significantly upregulated and significantly downregulated DEGs mainly participated in cell apoptosis-related pathways such as the phosphatidylinositol 3-kinase/Akt pathway and tumor necrosis factor signaling pathway. After 48 hours of culture, the cell apoptosis rates in both low-concentration capsaicin group and high-concentration capsaicin group were significantly lower than that in control group (with t values of 6.38 and 9.09, respectively, P < 0.05). The p-mTOR/mTOR ratio in cells in low-concentration capsaicin group was significantly higher than that in control group (t=2.74, P < 0.05). The p-Akt/Akt and p-mTOR/mTOR ratios in cells in high-concentration capsaicin group were significantly higher than those in control group (with t values of 4.43 and 3.33, respectively, P < 0.05). At 12 days after injury, the p-Akt/Akt and p-mTOR/mTOR ratios in wounds of diabetic mice in high-concentration capsaicin group were 0.470±0.044 and 0.549±0.106, respectively, which were significantly higher than 0.189±0.058 and 0.241±0.120 in control group (with t values of 6.67 and 3.36, respectively, P < 0.05).  Conclusions  Capsaicin can promote the healing of full-thickness skin defect wounds in diabetic mice by activating the Akt/mTOR signaling pathway in fibroblasts, thereby inhibiting apoptosis.

     

    • (1) This study preliminarily confirmed the efficacy of capsaicin in treating full-thickness skin defect wounds in diabetic mice, and explored and validated its underlying mechanisms.
    (2) Based on eukaryotic mRNA sequencing analysis, capsaicin was revealed to inhibit fibroblast (Fb) apoptosis and improve Fb function by activating the protein kinase B/mammalian target of rapamycin signaling pathway, thereby promoting the healing of full-thickness skin defect wounds in diabetic mice.
    FullText(HTML)
  • loading
    • References(41)
  • [1]
    夏如意, 唐棣, 杨斌. 丹参联合罗沙司他对糖尿病大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(4): 380-388. DOI: 10.3760/cma.j.cn501225-20231020-00124.
    [2]
    Xu J, Zhang H, Ye H. Research progress on the role of fascia in skin wound healing[J/OL]. Burns Trauma, 2025, 13: tkaf002[2025-02-10]. https://pubmed.ncbi.nlm.nih.gov/40248160/. DOI: 10.1093/burnst/tkaf002.
    [3]
    中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 国际内分泌代谢杂志, 2021, 41(5): 482-548. DOI: 10.3760/cma.j.cn121383-20210825-08063.
    [4]
    Deng S, Tai Y, Liu C, et al. Multifunctional microneedle-mediated photothermo-gas-ion synergic therapy accelerates MRSA infacted diabetic wound healing [J]. Mater Today Bio, 2025, 32: 101903. DOI: 10.1016/j.mtbio.2025.101903.
    [5]
    Wang F, Yao J, Zuo H, et al. Diverse-origin exosomes therapeutic strategies for diabetic wound healing[J]. Int J Nanomedicine, 2025, 20: 7375-7402. DOI: 10.2147/IJN.S519379.
    [6]
    Theocharidis G, Thomas BE, Sarkar D, et al. Single cell transcriptomic landscape of diabetic foot ulcers[J]. Nat Commun, 2022, 13(1): 181. DOI: 10.1038/s41467-021-27801-8.
    [7]
    Prabhakar V, Gupta D, Kanade P, et al. Diabetes-associated depression: the serotonergic system as a novel multifunctional target[J]. Indian J Pharmacol, 2015, 47(1): 4-10. DOI: 10.4103/0253-7613.150305.
    [8]
    Halabi J, Tarshoby M. Current situation and progress of diabetic foot care in the Middle East and North Africa region[J]. Diabetes Res Clin Pract, 2025, 226: 112318. DOI: 10.1016/j.diabres.2025.112318.
    [9]
    Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights[J]. Adv Ther, 2014, 31(8): 817-836. DOI: 10.1007/s12325-014-0140-x.
    [10]
    Botusan IR, Sunkari VG, Savu O, et al. Stabilization of HIF-1alpha is critical to improve wound healing in diabetic mice[J]. Proc Natl Acad Sci U S A, 2008, 105(49): 19426-19431. DOI: 10.1073/pnas.0805230105.
    [11]
    蒋能, 汤春丽, 吴慧娴, 等. 辣椒素药理活性及其药物代谢动力学的研究进展[J]. 天然产物研究与开发, 2022, 34(9): 1597-1606. DOI: 10.16333/j.1001-6880.2022.9.017.
    [12]
    Zhang Y, Shannonhouse J, Son H, et al. Regulatory action of calcium and calcium channels in pain pathways[J]. Int J Biol Sci, 2025, 21(8): 3726-3739. DOI: 10.7150/ijbs.110504.
    [13]
    Wang J, Zhang L, Zheng K. Efficacy of capsaicin for non-allergic rhinitis: an updated systematic review and meta-analysis[J]. Clin Rev Allergy Immunol, 2024, 67(1/2/3): 40-46. DOI: 10.1007/s12016-024-09005-2.
    [14]
    O'Leary C, McGahon MK, Ashraf S, et al. Involvement of TRPV1 and TRPV4 channels in retinal angiogenesis[J]. Invest Ophthalmol Vis Sci, 2019, 60(10): 3297-3309. DOI: 10.1167/iovs.18-26344.
    [15]
    Chen Y, Lei K, Li Y, et al. Synergistic effects of NO/H2S gases on antibacterial, anti-inflammatory, and analgesic properties in oral ulcers using a gas-releasing nanoplatform[J]. Acta Biomater, 2025, 194: 288-304. DOI: 10.1016/j.actbio.2025.01.013.
    [16]
    Chen YS, Lu MJ, Huang HS, et al. Mechanosensitive transient receptor potential vanilloid type 1 channels contribute to vascular remodeling of rat fistula veins[J]. J Vasc Surg, 2010, 52(5): 1310-1320. DOI: 10.1016/j.jvs.2010.05.095.
    [17]
    Zhu Z, Jiang Y, Li Z, et al. Sensory neuron transient receptor potential vanilloid-1 channel regulates angiogenesis through CGRP in vivo[J]. Front Bioeng Biotechnol, 2024, 12: 1338504. DOI: 10.3389/fbioe.2024.1338504.
    [18]
    Kotoda Y, Hishiyama S, Shim J, et al. A novel quaternary ammonium N-propylamiodarone bromide provides long-lasting analgesia against corneal pain[J]. Drug Des Devel Ther, 2024, 18: 6199-6208. DOI: 10.2147/DDDT.S486031.
    [19]
    Chen S, Wang H, Du J, et al. Near-infrared light-activatable, analgesic nanocomposite delivery system for comprehensive therapy of diabetic wounds in rats[J]. Biomaterials, 2024, 305: 122467. DOI: 10.1016/j.biomaterials.2024.122467.
    [20]
    Li X, Yuan D, Zhang P, et al. A neuron-mast cell axis regulates skin microcirculation in diabetes[J]. Diabetes, 2024, 73(10): 1728-1741. DOI: 10.2337/db23-0862.
    [21]
    Okada Y, Sumioka T, Reinach PS, et al. Roles of epithelial and mesenchymal TRP channels in mediating inflammatory fibrosis[J]. Front Immunol, 2021, 12: 731674. DOI: 10.3389/fimmu.2021.731674.
    [22]
    Yu Q, Shen Y, Xiao F, et al. Yuhong ointment ameliorates inflammatory responses and wound healing in scalded mice[J]. J Ethnopharmacol, 2023, 306: 116118. DOI: 10.1016/j.jep.2022.116118.
    [23]
    Zhou L, Chen L, Li T, et al. Cell-free adipose tissue extracts as a novel treatment for rosacea by downregulating TRPV1[J]. Sci Rep, 2024, 14(1): 21759. DOI: 10.1038/s41598-024-72593-8.
    [24]
    Huang CJ, Pu CM, Su SY, et al. Improvement of wound healing by capsaicin through suppression of the inflammatory response and amelioration of the repair process[J]. Mol Med Rep, 2023, 28(2): 155. DOI: 10.3892/mmr.2023.13042.
    [25]
    Avishai E, Yeghiazaryan K, Golubnitschaja O. Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine[J]. EPMA J, 2017, 8(1): 23-33. DOI: 10.1007/s13167-017-0081-y.
    [26]
    Zhang KW, Liu SY, Jia Y, et al. Insight into the role of DPP-4 in fibrotic wound healing[J]. Biomed Pharmacother, 2022, 151: 113143. DOI: 10.1016/j.biopha.2022.113143.
    [27]
    Sarkar Z, Singh H, Iqubal MK, et al. Involvement of macromolecules in 3D printing for wound healing management: a narrative review[J]. Int J Biol Macromol, 2024, 282(Pt 3): 136991. DOI: 10.1016/j.ijbiomac.2024.136991.
    [28]
    Kaur G, Narayanan G, Garg D, et al. Biomaterials-based regenerative strategies for skin tissue wound healing[J]. ACS Appl Bio Mater, 2022, 5(5): 2069-2106. DOI: 10.1021/acsabm.2c00035.
    [29]
    Azari Z, Nazarnezhad S, Webster TJ, et al. Stem cell-mediated angiogenesis in skin tissue engineering and wound healing[J]. Wound Repair Regen, 2022, 30(4): 421-435. DOI: 10.1111/wrr.13033.
    [30]
    Wang PH, Huang BS, Horng HC, et al. Wound healing[J]. J Chin Med Assoc, 2018, 81(2): 94-101. DOI: 10.1016/j.jcma.2017.11.002.
    [31]
    Woodley DT. Distinct fibroblasts in the papillary and reticular dermis: implications for wound healing[J]. Dermatol Clin, 2017, 35(1): 95-100. DOI: 10.1016/j.det.2016.07.004.
    [32]
    Julius D. TRP channels and pain[J]. Annu Rev Cell Dev Biol, 2013, 29: 355-384. DOI: 10.1146/annurev-cellbio-101011-155833.
    [33]
    Liao M, Cao E, Julius D, et al. Structure of the TRPV1 ion channel determined by electron cryo-microscopy[J]. Nature, 2013, 504(7478): 107-112. DOI: 10.1038/nature12822.
    [34]
    Sumioka T, Okada Y, Reinach PS, et al. Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse[J]. Invest Ophthalmol Vis Sci, 2014, 55(5): 3295-3302. DOI: 10.1167/iovs.13-13077.
    [35]
    Liu J, Huang S, Yu R, et al. TRPV1+ sensory nerves modulate corneal inflammation after epithelial abrasion via RAMP1 and SSTR5 signaling[J]. Mucosal Immunol, 2022, 15(5): 867-881. DOI: 10.1038/s41385-022-00533-8.
    [36]
    Maiese K. Warming up to new possibilities with the capsaicin receptor TRPV1: mTOR, AMPK, and erythropoietin[J]. Curr Neurovasc Res, 2017, 14(2): 184-189. DOI: 10.2174/1567202614666170313105337.
    [37]
    Liang Y, Chen P, Wang S, et al. SCFFBXW5-mediated degradation of AQP3 suppresses autophagic cell death through the PDPK1-AKT-MTOR axis in hepatocellular carcinoma cells[J]. Autophagy, 2024, 20(9): 1984-1999. DOI: 10.1080/15548627.2024.2353497.
    [38]
    Mossmann D, Park S, Hall MN. mTOR signalling and cellular metabolism are mutual determinants in cancer[J]. Nat Rev Cancer, 2018, 18(12): 744-757. DOI: 10.1038/s41568-018-0074-8.
    [39]
    Van Putte L, De Schrijver S, Moortgat P. The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: a systematic review[J]. Scars Burn Heal, 2016, 2: 2059513116676828. DOI: 10.1177/2059513116676828.
    [40]
    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.
    [41]
    农与乐, 吕叶辉. 环状RNA在糖尿病创面愈合中的作用机制研究进展[J]. 中华烧伤与创面修复杂志, 2023, 39(5): 487-490. DOI: 10.3760/cma.j.cn501225-20220727-00317.
    • 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(1)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (2703) PDF downloads(16) 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