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Abstract

Background

Diabetes and its associated complications encompass a range of comorbidities, including issues like impaired wound healing and chronic ulceration. It is very important to find an effective and economical way to manage diabetes and its complications. This review seeks to outline the mechanisms of action and potential drug targets of specific medicinal plants and derived compounds in healing diabetic wounds. Additionally, it aims to offer scientific evidence and research insights for their clinical application.

Methods

A literature search was conducted using Google Scholar, PubMed, and Scopus for articles on diabetic wound healing published between 2001 and December 2024. Using relevant keywords, 3122 articles were identified. After screening and applying exclusion criteria, 63 studies were selected and categorized into medicinal plants, plant-derived molecules, and clinical studies to explore potential therapeutic targets.

Results

Chronic diabetic wounds (DW) exhibit impaired healing across all wound repair phases, ., hemostasis, inflammation, proliferation, and remodelling. During hemostasis, defective coagulation and impaired platelet aggregation delay initial wound closure. The inflammatory phase is characterized by persistent inflammation, driven by elevated pro-inflammatory cytokines (., TNF-α, IL-6), reduced anti-inflammatory mediators, and dysregulated NF-κB, MAPK, and PI3K/Akt signalling pathways, which exacerbate tissue damage. In the proliferative phase, diminished levels of growth factors (., VEGF, PDGF) and disrupted signalling cascades impair angiogenesis, fibroblast proliferation, and extracellular matrix (ECM) synthesis, hindering tissue regeneration. The remodelling phase is compromised by chronic inflammation and an imbalance in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) activity, resulting in defective collagen reorganization, reduced tensile strength, and poor wound maturation. Herbal medicines demonstrate potential in ameliorating these impairments by modulating dysregulated pathways, exerting anti-inflammatory, antioxidant, and pro-angiogenic effects, and promoting balanced wound repair across all phases. Nevertheless, rigorous scientific validation and standardized documentation of traditional medicinal practices are essential to confirm their therapeutic efficacy and safety in DW management.

Conclusion

Diabetic wound management remains a major clinical challenge due to the limited efficacy and side effects of standard therapies. Medicinal plants and their bioactive compounds show promising healing potential through multi-targeted mechanisms. This review highlights a key research gap in the mechanistic understanding and clinical validation of traditional remedies, offering novel insights into targeting pathways like NF-κB, MAPK, and PI3K/Akt for improved diabetic wound care.

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2025-09-16
2025-12-05

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References

  1. Sandhya S. Kumar P.S. Vinod K.R. David Banji D.B. Kumar K. Plants as potent antidiabetic and wound healing agents-a review. Available from 2011 Available from: https://www.researchgate.net/publication/284042066_Plants_as_potent_antidiabetic_and_wound_healing_agents_-_A_review
    [Google Scholar]
  2. Shedoeva A. Leavesley D. Upton Z. Fan C. Wound healing and the use of medicinal plants. Evid. Based Complement. Alternat. Med. 2019 2019 1 1 30 10.1155/2019/2684108 31662773
    [Google Scholar]
  3. Adedapo A.A. Ogunmiluyi I.O. The use of natural products in the management of diabetes: The current trends. J. Drug Deliv. Ther. 2020 10 1 153 162 10.22270/jddt.v10i1.3839
    [Google Scholar]
  4. Pradeepa R. Mohan V. Epidemiology of type 2 diabetes in India. Indian J. Ophthalmol. 2021 69 11 2932 2938 10.4103/ijo.IJO_1627_21 34708726
    [Google Scholar]
  5. Zhang P. Lu J. Jing Y. Tang S. Zhu D. Bi Y. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis. Ann. Med. 2017 49 2 106 116 10.1080/07853890.2016.1231932 27585063
    [Google Scholar]
  6. Panigrahi S.K. Majumdar S. Assessment of predictors of diabetic foot ulcers in a tertiary care hospital of Maharashtra, India: A cross-sectional comparative study. J. Educ. Health Promot. 2023 12 1 101 10.4103/jehp.jehp_1868_21 37288394
    [Google Scholar]
  7. Edmonds M. Manu C. Vas P. The current burden of diabetic foot disease. J. Clin. Orthop. Trauma 2021 17 88 93 10.1016/j.jcot.2021.01.017 33680841
    [Google Scholar]
  8. Kale D.S. Karande G.S. Datkhile K.D. Diabetic foot ulcer in India: Aetiological trends and bacterial diversity. Indian J. Endocrinol. Metab. 2023 27 2 107 114 10.4103/ijem.ijem_458_22 37292074
    [Google Scholar]
  9. Oguntibeju O.O. Medicinal plants and their effects on diabetic wound healing. Vet. World 2019 12 5 653 663 10.14202/vetworld.2019.653‑663 31327900
    [Google Scholar]
  10. Burgess J.L. Wyant W.A. Abdo Abujamra B. Kirsner R.S. Jozic I. Diabetic wound-healing science. Medicina 2021 57 10 1072 10.3390/medicina57101072 34684109
    [Google Scholar]
  11. Li J. Zhang T. Pan M. Nanofiber/hydrogel core–shell scaffolds with three-dimensional multilayer patterned structure for accelerating diabetic wound healing. J. Nanobiotechnology 2022 20 1 28 10.1186/s12951‑021‑01208‑5 34998407
    [Google Scholar]
  12. Hirapara H. Ghori V. Anovadiya A. Baxi S. Tripathi C. Effects of ethanolic extract of Jasminum grandiflorum Linn. flowers on wound healing in diabetic Wistar albino rats. Avicenna J. Phytomed. 2017 7 5 401 408 29062801
    [Google Scholar]
  13. Getahun A. Kifle Z.D. Ambikar D. Atnafie S.A. In vivo evaluation of 80% methanolic leaves crude extract and solvent fractions of buddleja polystachya fresen (buddlejaceae) for wound healing activity in normal and diabetic mice. Metab Open 2021 11 100110 10.1016/j.metop.2021.100110 34355159
    [Google Scholar]
  14. Patel S. Srivastava S. Singh M.R. Singh D. Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed. Pharmacother. 2019 112 108615 10.1016/j.biopha.2019.108615 30784919
    [Google Scholar]
  15. Brem H. Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J. Clin. Invest. 2007 117 5 1219 1222 10.1172/JCI32169 17476353
    [Google Scholar]
  16. Yadu N. Singh M. Singh D. Keshavkant S. Mechanistic insights of diabetic wound: Healing process, associated pathways and microRNA-based delivery systems. Int. J. Pharm. 2025 670 125117 10.1016/j.ijpharm.2024.125117 39719258
    [Google Scholar]
  17. Schürmann C. Goren I. Linke A. Pfeilschifter J. Frank S. Deregulated unfolded protein response in chronic wounds of diabetic ob/ob mice: A potential connection to inflammatory and angiogenic disorders in diabetes-impaired wound healing. Biochem. Biophys. Res. Commun. 2014 446 1 195 200 10.1016/j.bbrc.2014.02.085 24583133
    [Google Scholar]
  18. Galkowska H. Wojewodzka U. Olszewski W.L. Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair Regen. 2006 14 5 558 565 10.1111/j.1743‑6109.2006.00155.x 17014667
    [Google Scholar]
  19. Sharp A. Clark J. Diabetes and its effects on wound healing. Nurs. Stand. 2011 25 45 41 47 10.7748/ns.25.45.41.s48 21850847
    [Google Scholar]
  20. Park J.E. Barbul A. Understanding the role of immune regulation in wound healing. Am. J. Surg. 2004 187 5 S11 S16 10.1016/S0002‑9610(03)00296‑4 15147986
    [Google Scholar]
  21. Lucas T. Waisman A. Ranjan R. Differential roles of macrophages in diverse phases of skin repair. J. Immunol. 2010 184 7 3964 3977 10.4049/jimmunol.0903356 20176743
    [Google Scholar]
  22. Xu F. Zhang C. Graves D.T. Abnormal cell responses and role of TNF-in impaired diabetic wound healing. BioMed Res. Int. 2013 2013 1 9 10.1155/2013/754802
    [Google Scholar]
  23. Spampinato S.F. Caruso G.I. De Pasquale R. Sortino M.A. Merlo S. The treatment of impaired wound healing in diabetes: Looking among old drugs. Pharmaceuticals 2020 13 4 60 10.3390/ph13040060 32244718
    [Google Scholar]
  24. Lobmann R. Zemlin C. Motzkau M. Reschke K. Lehnert H. Expression of matrix metalloproteinases and growth factors in diabetic foot wounds treated with a protease absorbent dressing. J. Diabetes Complications 2006 20 5 329 335 10.1016/j.jdiacomp.2005.08.007 16949521
    [Google Scholar]
  25. Graça M.F.P. de Melo-Diogo D. Correia I.J. Moreira A.F. Electrospun asymmetric membranes as promising wound dressings: A review. Pharmaceutics 2021 13 2 183 10.3390/pharmaceutics13020183 33573313
    [Google Scholar]
  26. Salazar J.J. Ennis W.J. Koh T.J. Diabetes medications: Impact on inflammation and wound healing. J. Diabetes Complications 2016 30 4 746 752 10.1016/j.jdiacomp.2015.12.017 26796432
    [Google Scholar]
  27. Radhika P.V. Kumar K.V. Herbal hydrogel for wound healing: A review. Int J Pharma Res Health Sci 2017 5 2 1616 1622
    [Google Scholar]
  28. Karimi A. Majlesi M. Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J. Nephropharmacol. 2015 4 1 27 30 28197471
    [Google Scholar]
  29. Sharma A. Khanna S. Kaur G. Singh I. Medicinal plants and their components for wound healing applications. Future J Pharm Sci 2021 7 1 1 13
    [Google Scholar]
  30. Nasiry D. Khalatbary A.R. Ghaemi A. Ebrahimzadeh M.A. Hosseinzadeh M.H. Topical administration of Juglans regia L. leaf extract accelerates diabetic wound healing. BMC Complement Med Ther 2022 22 1 255 10.1186/s12906‑022‑03735‑6 36192711
    [Google Scholar]
  31. Mumtaz R. Zubair M. Khan M.A. Muzammil S. Siddique M.H. Extracts of Eucalyptus alba promote diabetic wound healing by inhibiting α-glucosidase and stimulating cell proliferation. Evid. Based Complement. Alternat. Med. 2022 2022 1 12 10.1155/2022/4953105 35463094
    [Google Scholar]
  32. Adeleke O. Oboh G. Adefegha S. Osesusi A. Effect of aqueous extract from root and leaf of Sphenocentrum jollyanum pierre on wounds of diabetic rats: Influence on wound tissue cytokines, vascular endothelial growth factor and microbes. J. Ethnopharmacol. 2022 293 115266 10.1016/j.jep.2022.115266 35398496
    [Google Scholar]
  33. Perez G.R.M. Vargas S.R. Ortiz H.Y.D. Wound healing properties of Hylocereus undatus on diabetic rats. Phytother. Res. 2005 19 8 665 668 10.1002/ptr.1724 16177967
    [Google Scholar]
  34. Ponrasu T. Suguna L. Efficacy of Annona squamosa L in the synthesis of glycosaminoglycans and collagen during wound repair in streptozotocin induced diabetic rats. BioMed Res. Int. 2014 2014 1 10 10.1155/2014/124352 25003104
    [Google Scholar]
  35. Ponrasu T. Subamekala M.K. Ganeshkuma M. Suguna L. Role of Annona squamosa on antioxidants during wound healing in streptozotocin-nicotinamide induced diabetic rats. J. Pharmacogn. Phytochem. 2013 2 4
    [Google Scholar]
  36. Nayak S. Influence of ethanol extract of Vinca rosea on wound healing in diabetic rats. Online J. Biol. Sci. 2006 6 2 51 55 10.3844/ojbsci.2006.51.55
    [Google Scholar]
  37. Singh S.N. Vats P. Suri S. Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats. J. Ethnopharmacol. 2001 76 3 269 277 10.1016/S0378‑8741(01)00254‑9 11448549
    [Google Scholar]
  38. Singh A. Singh P.K. Singh R.K. Antidiabetic and wound healing activity of Catharanthus roseus L. in STZ-induced diabetic mice. American J Phyt Clin Therap 2014 2 686 692
    [Google Scholar]
  39. Altan A. Aras M.H. Damlar I. Gökçe H. Özcan O. Alpaslan C. The effect of Hypericum Perforatum on wound healing of oral mucosa in diabetic rats. Eur. Oral Res. 2019 52 3 143 149 10.26650/eor.2018.505 30775718
    [Google Scholar]
  40. Altıparmak M. Eskitaşçıoğlu T. Comparison of systemic and topical Hypericum perforatum on diabetic surgical wounds. J. Invest. Surg. 2018 31 1 29 37 10.1080/08941939.2016.1272654 28107097
    [Google Scholar]
  41. Yadollah-Damavandi S. Chavoshi-Nejad M. Jangholi E. Topical Hypericum perforatum improves tissue regeneration in full-thickness excisional wounds in diabetic rat model. Evid. Based Complement. Alternat. Med. 2015 2015 1 245328 26417372
    [Google Scholar]
  42. Shetty S.B. Pemminati S. Evaluation of Centella asiatica leaf extract for wound healing in streptozotocin-induced diabetic rats. Res. J. Pharm. Biol. Chem. Sci. 2013 4 2 1082 1090
    [Google Scholar]
  43. Alsarayreh A.Z. Attalah Oran S. Shakhanbeh J.M. In vitro and in vivo wound healing activities of Globularia arabica leaf methanolic extract in diabetic rats. J. Cosmet. Dermatol. 2022 21 10 4888 4900 10.1111/jocd.14882 35212131
    [Google Scholar]
  44. Alsarayreh A.Z. Oran S.A. Shakhanbeh J.M. Effect of Rhus coriaria L. methanolic fruit extract on wound healing in diabetic and non‐diabetic rats. J. Cosmet. Dermatol. 2022 21 8 3567 3577 10.1111/jocd.14668 34928525
    [Google Scholar]
  45. Nayak S.B. Pinto Pereira L. Maharaj D. Wound healing activity of Carica papaya L. in experimentally induced diabetic rats. Indian J. Exp. Biol. 2007 45 8 739 743 17877152
    [Google Scholar]
  46. Ajani R. Ogunbiyi K. Carica papaya latex accelerates wound healing in diabetic Wistar rats. European J. Med. Plants 2015 9 3 1 12 10.9734/EJMP/2015/17758
    [Google Scholar]
  47. Perez Gutierrez R.M. Vargas S.R. Evaluation of the wound healing properties of Acalypha langiana in diabetic rats. Fitoterapia 2006 77 4 286 289 10.1016/j.fitote.2006.03.011 16713129
    [Google Scholar]
  48. Silva A.C.C. Eugênio A.N. Mariano S.S. Topical application of Azadirachta indica improves epidermal wound healing in hyperglycemic rats. Comp. Clin. Pathol. 2021 30 3 461 472 10.1007/s00580‑021‑03240‑1
    [Google Scholar]
  49. Manhas D. Malairaman U. Impact of Moringa oleifera hydro-alcoholic bark extract on diabetic wound healing: A topical approach. Int. J. Low. Extrem. Wounds 2024 15347346241297829 10.1177/15347346241297829 39636130
    [Google Scholar]
  50. Babu Natarajan S. Das S.K. Chandran S.P. Moringa oleifera leaf extract loaded hydrogel for diabetic wound healing. Malaysian J Med Res 2018 2 2 35 41 10.31674/mjmr.2018.v02i02.006
    [Google Scholar]
  51. Anwer T. Safhi M.M. Makeen H.A. Antidiabetic potential of Moringa oleifera Lam. leaf extract in type 2 diabetic rats, and its mechanism of action. Trop. J. Pharm. Res. 2021 20 1 95 103 10.4314/tjpr.v20i1.15
    [Google Scholar]
  52. Hernandez-Hernandez A.B. Alarcon-Aguilar F.J. Garcia-Lorenzana M. Rodriguez-Monroy M.A. Canales-Martinez M.M. Jatropha neopauciflora Pax latex exhibits wound-healing effect in normal and diabetic mice. J. Evid-Based Integr. Med. 2021 26 10.1177/2515690X20986762
    [Google Scholar]
  53. Teoh S.L. Latiff A.A. Das S. The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin. Clin. Exp. Dermatol. 2009 34 7 815 822 10.1111/j.1365‑2230.2008.03117.x
    [Google Scholar]
  54. Jayakumari S. Sangeetha M. Ali S. Formulation and evaluation of herbal gel from tannin-enriched fraction of Psidium guajava Linn. leaves for diabetic wound healing. Inter J Green Pharm 2018 12 3 S490
    [Google Scholar]
  55. Hussan F Teoh SL Muhamad N Mazlan M Latiff AA Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression J Wound Care 2014 23 8 400 407 402 404 407 10.12968/jowc.2014.23.8.400 25139598
    [Google Scholar]
  56. Pirbalouti A.G. Azizi S. Koohpayeh A. Hamedi B. Wound healing activity of Malva sylvestris and Punica granatum in alloxan-induced diabetic rats. Acta Pol. Pharm. 2010 67 5 511 516 20873419
    [Google Scholar]
  57. Karim S. Alkreathy H.M. Ahmad A. Khan M.I. Effects of methanolic extract based-gel from Saudi pomegranate peels with enhanced healing potential on excision wounds in diabetic rats. Front. Pharmacol. 2021 12 704503 10.3389/fphar.2021.704503 34122120
    [Google Scholar]
  58. Abu-Al-Basal M.A. Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice. J. Ethnopharmacol. 2010 131 2 443 450 10.1016/j.jep.2010.07.007 20633625
    [Google Scholar]
  59. Umasankar K. Nambikkairaj B. Backyavathy D.M. Effect of topical treatment of Rosmarinus officinalis essential oil on wound healing in STZ-induced diabetic rats. Nature Environ Poll Tech 2012 11 4 607 611
    [Google Scholar]
  60. Khan M.A. Shahzadi T. Malik S.A. Shahid M. Ismail M. Zubair M. Pharmacognostic evaluation of turmeric (Curcuma longa) extracts in diabetic wound healing. J. Anim. Plant Sci. 2019 29 1 68 74
    [Google Scholar]
  61. Soman S. Rajamanickam C. Rauf A.A. Madambath I. Molecular mechanisms of the antiglycative and cardioprotective activities of Psidium guajava leaves in the rat diabetic myocardium. Pharm. Biol. 2016 54 12 3078 3085 10.1080/13880209.2016.1207090 27418019
    [Google Scholar]
  62. Alqahtani A.S. Li K.M. Razmovski-Naumovski V. Kam A. Alam P. Li G.Q. Attenuation of methylglyoxal-induced glycation and cellular dysfunction in wound healing by Centella cordifolia. Saudi J. Biol. Sci. 2021 28 1 813 824 10.1016/j.sjbs.2020.11.016 33424371
    [Google Scholar]
  63. Khalid M. Petroianu G. Adem A. Advanced glycation end products and diabetes mellitus: Mechanisms and perspectives. Biomolecules 2022 12 4 542 10.3390/biom12040542 35454131
    [Google Scholar]
  64. Ding Y. Ding X. Zhang H. Li S. Yang P. Tan Q. Relevance of NLRP3 inflammasome-related pathways in the pathology of diabetic wound healing and possible therapeutic targets. Oxid. Med. Cell. Longev. 2022 2022 1 9687925 10.1155/2022/9687925 35814271
    [Google Scholar]
  65. Jindam A. Yerra V.G. Kumar A. Nrf2: A promising trove for diabetic wound healing. Ann. Transl. Med. 2017 5 23 469 10.21037/atm.2017.09.03 29285502
    [Google Scholar]
  66. Mirza R.E. Fang M.M. Weinheimer-Haus E.M. Ennis W.J. Koh T.J. Sustained inflammasome activity in macrophages impairs wound healing in type 2 diabetic humans and mice. Diabetes 2014 63 3 1103 1114 10.2337/db13‑0927 24194505
    [Google Scholar]
  67. Nelson K.K. Melendez J.A. Mitochondrial redox control of matrix metalloproteinases. Free Radic. Biol. Med. 2004 37 6 768 784 10.1016/j.freeradbiomed.2004.06.008 15304253
    [Google Scholar]
  68. Sargowo D. Handaya A.Y. Tjokroprawiro A. The effect of aloe gel in enhancing angiogenesis in diabetic wound healing. Indones. Biomed. J. 2012 3 3 204 10.18585/inabj.v3i3.152
    [Google Scholar]
  69. Atiba A. Ueno H. Uzuka Y. The effect of aloe vera oral administration on cutaneous wound healing in type 2 diabetic rats. J. Vet. Med. Sci. 2011 73 5 583 589 10.1292/jvms.10‑0438 21178319
    [Google Scholar]
  70. Zhao D. Luo Z. Li S. Liu S. Wang C. Metabolomics revealed the effects of Momordica charantia L. saponins on diabetic hyperglycemia and wound healing in mice. Foods 2024 13 19 3163 10.3390/foods13193163 39410199
    [Google Scholar]
  71. Farooq M.A. Ali S. Sulayman R. Therapeutic applications of garlic and turmeric for the diabetic wound healing in mice. J. Burn Care Res. 2023 44 4 800 809 10.1093/jbcr/irac169 36331804
    [Google Scholar]
  72. Singla R. Soni S. Patial V. In vivo diabetic wound healing potential of nanobiocomposites containing bamboo cellulose nanocrystals impregnated with silver nanoparticles. Int. J. Biol. Macromol. 2017 105 Pt 1 45 55 10.1016/j.ijbiomac.2017.06.109 28669805
    [Google Scholar]
  73. Fei J. Ling Y.M. Zeng M.J. Zhang K.W. Shixiang plaster, a traditional Chinese medicine, promotes healing in a rat model of diabetic ulcer through the receptor for advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) and vascular endothelial growth factor (VEGF)/vascular cell adhesion molecule-1 (VCAM-1)/endothelial nitric oxide synthase (eNOS) signaling pathways. Med. Sci. Monit. 2019 25 9446 9457 10.12659/MSM.918268 31825949
    [Google Scholar]
  74. Pereira J.A. Oliveira I. Sousa A. Ferreira I.C.F.R. Bento A. Estevinho L. Bioactive properties and chemical composition of six walnut (Juglans regia L.) cultivars. Food Chem. Toxicol. 2008 46 6 2103 2111 10.1016/j.fct.2008.02.002 18334279
    [Google Scholar]
  75. Zhao M.H. Jiang Z.T. Liu T. Li R. Flavonoids in Juglans regia L. leaves and evaluation of in vitro antioxidant activity via intracellular and chemical methods. Scient World J 2014 2014 1 6 10.1155/2014/303878 25133218
    [Google Scholar]
  76. Al-Ghanayem A.A. Alhussaini M.S. Asad M. Joseph B. Moringa oleifera leaf extract promotes healing of infected wounds in diabetic rats: Evidence of antimicrobial, antioxidant and proliferative properties. Pharmaceuticals 2022 15 5 528 10.3390/ph15050528 35631354
    [Google Scholar]
  77. Khan I.A. Lodhi A.H. Munawar S.H. Manzoor A. Raza M.A. Formulation and evaluation of allicin and curcumin gel improves normal and diabetic ulcers in rabbits. Lat. Am. J. Pharm. 2018 37 8 1602 1607
    [Google Scholar]
  78. Peng Y. Ao M. Dong B. Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug Des. Devel. Ther. 2021 15 4503 4525 10.2147/DDDT.S327378 34754179
    [Google Scholar]
  79. Xia S. Weng T. Jin R. Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds. Burns Trauma 2022 10 tkac001 10.1093/burnst/tkac001 35291229
    [Google Scholar]
  80. Mitra S. Mateti T. Ramakrishna S. Laha A. A review on curcumin-loaded electrospun nanofibers and their application in modern medicine. J. Miner. Met. Mater. Soc. 2022 74 9 3392 3407 10.1007/s11837‑022‑05180‑9 35228788
    [Google Scholar]
  81. Liu J. Chen Z. Wang J. Encapsulation of curcumin nanoparticles with MMP9-responsive and thermos-sensitive hydrogel improves diabetic wound healing. ACS Appl. Mater. Interfaces 2018 10 19 16315 16326 10.1021/acsami.8b03868 29687718
    [Google Scholar]
  82. Taghavifar S. Afroughi F. Saadati Keyvan M. Curcumin nanoparticles improved diabetic wounds infected with methicillin-resistant Staphylococcus aureus sensitized with HAMLET. Int. J. Low. Extrem. Wounds 2022 21 2 141 153 10.1177/1534734620933079 32594792
    [Google Scholar]
  83. Gao S.Q. Chang C. Niu X.Q. Li L.J. Zhang Y. Gao J.Q. Topical application of Hydroxysafflor Yellow A accelerates the wound healing in streptozotocin induced T1DM rats. Eur. J. Pharmacol. 2018 823 72 78 10.1016/j.ejphar.2018.01.018 29408092
    [Google Scholar]
  84. Kant V. Jangir B.L. Sharma M. Kumar V. Joshi V.G. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol. Immunotoxicol. 2021 43 5 536 553 10.1080/08923973.2021.1950758 34278923
    [Google Scholar]
  85. Özay Y. Güzel S. Yumrutaş Ö. Wound healing effect of kaempferol in diabetic and nondiabetic rats. J. Surg. Res. 2019 233 284 296 10.1016/j.jss.2018.08.009 30502261
    [Google Scholar]
  86. Chanu N.R. Gogoi P. Barbhuiya P.A. Dutta P.P. Pathak M.P. Sen S. Natural flavonoids as potential therapeutics in the management of diabetic wound: A review. Curr. Top. Med. Chem. 2023 23 8 690 710 10.2174/1568026623666230419102140 37114791
    [Google Scholar]
  87. Naseeb M Albajri E Almasaudi A Rutin promotes wound healing by inhibiting oxidative stress and inflammation in metformin-controlled diabetes in rats. ACS Omega 2024 2024 9 30 acsomega.3c05595 10.1021/acsomega.3c05595 39100330
    [Google Scholar]
  88. Kandhare A.D. Ghosh P. Bodhankar S.L. Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats. Chem. Biol. Interact. 2014 219 101 112 10.1016/j.cbi.2014.05.012 24880026
    [Google Scholar]
  89. Zhang E.Y. Gao B. Shi H.L. 20(S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice. Exp. Mol. Med. 2017 49 10 e387 e7 10.1038/emm.2017.151 29075038
    [Google Scholar]
  90. Zeng Z. Zhu B.H. Arnebin-1 promotes the angiogenesis of human umbilical vein endothelial cells and accelerates the wound healing process in diabetic rats. J. Ethnopharmacol. 2014 154 3 653 662 10.1016/j.jep.2014.04.038 24794013
    [Google Scholar]
  91. Ren J. Yang M. Chen J. Ma S. Wang N. Anti-inflammatory and wound healing potential of kirenol in diabetic rats through the suppression of inflammatory markers and matrix metalloproteinase expressions. Biomed. Pharmacother. 2020 129 110475 10.1016/j.biopha.2020.110475 32768960
    [Google Scholar]
  92. Lodhi S. Jain A.P. Sharma V.K. Singhai A.K. Wound-healing effect of flavonoid-rich fraction from Tephrosia purpurea Linn. on STZ-induced diabetic rats. J. Herbs Spices Med. Plants 2013 19 2 191 205 10.1080/10496475.2013.779620
    [Google Scholar]
  93. Sanapalli B.K.R. Yele V. Sigalapalli D.K. Forging of nicotine for the effective management of diabetic wounds: A hybrid of scaffold hopping and molecular dynamics simulation approaches. Arab. J. Chem. 2022 15 2 103585 10.1016/j.arabjc.2021.103585
    [Google Scholar]
  94. Wang L. Xia K. Han L. Local administration of ginkgolide B using a hyaluronan-based hydrogel improves wound healing in diabetic mice. Front. Bioeng. Biotechnol. 2022 10 898231 10.3389/fbioe.2022.898231 35694224
    [Google Scholar]
  95. Shao Y. Dang M. Lin Y. Xue F. Evaluation of wound healing activity of plumbagin in diabetic rats. Life Sci. 2019 231 116422 10.1016/j.lfs.2019.04.048 31059689
    [Google Scholar]
  96. Hordyjewska A. Ostapiuk A. Horecka A. Kurzepa J. Betulin and betulinic acid: Triterpenoids derivatives with a powerful biological potential. Phytochem. Rev. 2019 18 3 929 951 10.1007/s11101‑019‑09623‑1
    [Google Scholar]
  97. Xie W. Hu W. Huang Z. Betulinic acid accelerates diabetic wound healing by modulating hyperglycemia-induced oxidative stress, inflammation and glucose intolerance. Burns Trauma 2022 10 tkac007 10.1093/burnst/tkac007 35415192
    [Google Scholar]
  98. Li J. Chou H. Li L. Li H. Cui Z. Wound healing activity of neferine in experimental diabetic rats through the inhibition of inflammatory cytokines and nrf-2 pathway. Artif. Cells Nanomed. Biotechnol. 2020 48 1 96 106 10.1080/21691401.2019.1699814 31852261
    [Google Scholar]
  99. Deng L. Du C. Song P. The role of oxidative stress and antioxidants in diabetic wound healing. Oxid. Med. Cell. Longev. 2021 2021 1 8852759 10.1155/2021/8852759 33628388
    [Google Scholar]
  100. Song J. Liu A. Liu B. Natural biologics accelerate healing of diabetic foot ulcers by regulating oxidative stress. Front. Biosci. 2022 27 10 285 10.31083/j.fbl2710285 36336859
    [Google Scholar]
  101. Chen L.Y. Cheng H.L. Kuan Y.H. Liang T.J. Chao Y.Y. Lin H.C. Therapeutic potential of luteolin on impaired wound healing in STZ-induced rats. Biomedicines 2021 9 7 761 10.3390/biomedicines9070761 34209369
    [Google Scholar]
  102. Accipe L. Abadie A. Neviere R. Bercion S. Antioxidant activities of natural compounds from Caribbean plants to enhance diabetic wound healing. Antioxidants 2023 12 5 1079 10.3390/antiox12051079 37237945
    [Google Scholar]
  103. Yuan X. Han L. Fu P. Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways. Lab. Invest. 2018 98 6 783 798 10.1038/s41374‑018‑0025‑8 29463877
    [Google Scholar]
  104. Fathi A.N. Sakhaie M.H. Babaei S. Babaei S. Slimabad F. Babaei S. Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: An experimental model. J. Wound Care 2020 29 9 488 495 10.12968/jowc.2020.29.9.488 32924815
    [Google Scholar]
  105. Yassien R.I. El-Ghazouly D.E.S. The role of hesperidin on healing an incised wound in an experimentally induced diabetic adult male albino rats. Histological and immunohistochemical study. Egypt. J. Histol. 2021 44 1 144 162
    [Google Scholar]
  106. Fu J. Huang J. Lin M. Xie T. You T. Quercetin promotes diabetic wound healing via switching macrophages from M1 to M2 polarization. J. Surg. Res. 2020 246 213 223 10.1016/j.jss.2019.09.011 31606511
    [Google Scholar]
  107. Sanapalli B.K.R. Yele V. Singh M.K. Thaggikuppe Krishnamurthy P. Karri V.V.S.R. Preclinical models of diabetic wound healing: A critical review. Biomed. Pharmacother. 2021 142 111946 10.1016/j.biopha.2021.111946 34339915
    [Google Scholar]
  108. Berry-Kilgour C. Cabral J. Wise L. Advancements in the delivery of growth factors and cytokines for the treatment of cutaneous wound indications. Adv. Wound Care 2021 10 11 596 622 10.1089/wound.2020.1183 33086946
    [Google Scholar]
  109. Wang X. Yuan C.X. Xu B. Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J. Diabetes 2022 13 12 1049 1065 10.4239/wjd.v13.i12.1049 36578871
    [Google Scholar]
  110. Agharazi M. Gazerani S. Huntington M.K. Topical turmeric ointment in the treatment of diabetic foot ulcers: A randomized, placebo-controlled study. Int. J. Low. Extrem. Wounds 2022 15347346221143222 10.1177/15347346221143222 36514270
    [Google Scholar]
  111. Malini H. Sari Y.K. Oktarina E. Effect of Aloe vera gel on wound healing process for diabetic foot ulcers: A pilot study. Gac. Med. Caracas 2022 130 5S 10.47307/GMC.2022.130.s5.15
    [Google Scholar]
  112. Labichella ML The use of an extract of hypericum perforatum and azadirachta indica in advanced diabetic foot: An unexpected outcome BMJ Case Rep 2013 2013 10.1136/bcr‑2012‑007299
    [Google Scholar]
  113. Fatimah M. Alam S.S. Hamiduddin. Importance of raw papaya dressing in diabetic foot ulcer– A case report. European J Biomed Pharm Sci 2015 2 3 504 508
    [Google Scholar]
  114. Kuo Y.S. Chien H.F. Lu W. Plectranthus amboinicus and Centella asiatica cream for the treatment of diabetic foot ulcers. Evid. Based Complement. Alternat. Med. 2012 2012 1 9 10.1155/2012/418679 22693530
    [Google Scholar]
  115. Fsj A.J.M. Vaithiyanathan R. Vijayaragavan R. Effectiveness of conventional and herbal treatment on diabetic foot ulcer using Texas and Wagner wound scales. Int. J. Nurs. Educ. 2017 9 4 1 5 10.5958/0974‑9357.2017.00087.3
    [Google Scholar]
  116. Izundu M.I. Anyamene C.O. Okoro N.C. Okoli U.O. Antimicrobial effects of Azadrachita indica leaf extracts on Escherichia coli isolated from infected diabetic wounds. Bioscientist J 2021 9 1 99 108
    [Google Scholar]
  117. Zeng Y.Q. He J.T. Hu B.Y. Li W. Deng J. Lin Q.L. Virgin coconut oil: A comprehensive review of antioxidant activity and mechanisms contributed by phenolic compounds. Crit. Rev. Food Sci. Nutr. 2022 1 24 35997296
    [Google Scholar]
  118. Farhat F. Sohail S.S. Siddiqui F. Irshad R.R. Madsen D.Ø. Curcumin in wound healing-A bibliometric analysis. Life 2023 13 1 143 10.3390/life13010143 36676091
    [Google Scholar]
  119. Karimi Z. Behnammoghadam M. Rafiei H. Impact of olive oil and honey on healing of diabetic foot: A randomized controlled trial. Clin. Cosmet. Investig. Dermatol. 2019 12 347 354 10.2147/CCID.S198577 31190942
    [Google Scholar]
  120. Abdoli A. Shahbazi R. Zoghi G. The effect of topical olive oil dressing on the healing of grade 1 and 2 diabetic foot ulcers: An assessor-blind randomized controlled trial in type 2 diabetes patients. Diabetes Metab. Syndr. 2022 16 12 102678 10.1016/j.dsx.2022.102678 36459908
    [Google Scholar]
  121. Al-Irayfawee N.S.H. Al-Biatey D.K.A.A. Al-Mubarak Z.A.H. Effectiveness of Punica granatum and propolis: A new dressing method in the management of diabetic foot ulceration. Indian J Forensic Med Toxicol 2019 13 1 314 320 10.5958/0973‑9130.2019.00062.8
    [Google Scholar]
  122. Jayalakshmi M. Effect of neem leaves extract irrigation on the wound healing outcome in nurse managed diabetic foot ulcers. Natl. J. Physiol. Pharm. Pharmacol. 2020 11 1 1 10.5455/njppp.2021.10.09238202008092020
    [Google Scholar]
  123. Jayalakshmi M.S. Thenmozhi P. Vijayaraghavan R. Plant leaves extract irrigation on wound healing in diabetic foot ulcers. Evid. Based Complement. Alternat. Med. 2021 2021 9924725 34055026
    [Google Scholar]
  124. Mokhtari M. Razzaghi R. Momen-Heravi M. The effects of curcumin intake on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial. Phytother. Res. 2021 35 4 2099 2107 10.1002/ptr.6957 33200488
    [Google Scholar]
  125. Paocharoen V. The efficacy and side effects of oral Centella asiatica extract for wound healing promotion in diabetic wound patients. J. Med. Assoc. Thai. 2010 93 7 S166 S170 21298840
    [Google Scholar]
  126. El Hage R. Knippschild U. Arnold T. Hinterseher I. Stem cell-based therapy: A promising treatment for diabetic foot ulcer. Biomedicines 2022 10 7 1507 10.3390/biomedicines10071507 35884812
    [Google Scholar]
  127. Flynn K. Mahmoud N.N. Sharifi S. Gould L.J. Mahmoudi M. Chronic wound healing models. ACS Pharmacol. Transl. Sci. 2023 6 5 783 801 10.1021/acsptsci.3c00030 37200810
    [Google Scholar]
  128. Poblete Jara C. Nogueira G. Morari J. An older diabetes-induced mice model for studying skin wound healing. PLoS One 2023 18 2 0281373 10.1371/journal.pone.0281373 36800369
    [Google Scholar]
  129. Aljamal D. Iyengar P.S. Nguyen T.T. Translational challenges in drug therapy and delivery systems for treating chronic lower extremity wounds. Pharmaceutics 2024 16 6 750 10.3390/pharmaceutics16060750 38931872
    [Google Scholar]
  130. Kandemir K. Tomas M. McClements D.J. Capanoglu E. Recent advances on the improvement of quercetin bioavailability. Trends Food Sci. Technol. 2022 119 192 200 10.1016/j.tifs.2021.11.032
    [Google Scholar]
  131. Quispe C. Herrera-Bravo J. Javed Z. Therapeutic applications of curcumin in diabetes: A review and perspective. BioMed Res. Int. 2022 2022 1 1375892 10.1155/2022/1375892 35155670
    [Google Scholar]
  132. Ong E. Extraction methods and chemical standardization of botanicals and herbal preparations. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2004 812 1-2 23 33 10.1016/S1570‑0232(04)00647‑6 15556486
    [Google Scholar]
/content/journals/cdrr/10.2174/0125899775395717250903190844
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A Comprehensive Review on the Role of Medicinal Plants in the Management of Diabetic Wound: A Mechanistic Insight
Bentham Science Publishers ; https://doi.org/10.2174/0125899775395717250903190844
/content/journals/cdrr/10.2174/0125899775395717250903190844
/content/journals/cdrr/10.2174/0125899775395717250903190844
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  • Article Type:     Review Article
Keywords: medicinal plants ; molecular targets ; clinical studies ; wound healing ; plant-derived molecules ; Diabetes

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