Skip to content
2000
Volume 22, Issue 5
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Aim

Preclinical Evaluation of Fisetin in the Management of Diabetic Foot Ulcer in Wistar Rats.

Introduction

Diabetic foot ulcer (DFU) is a complication of diabetes mellitus, often leading to non-traumatic amputations and significantly impacting patient morbidity. Globally, the prevalence of DFU ranges from 9.1 to 26.1 million annually. A 2022 meta-analysis revealed that 6.3% of diabetic adults (33 million) are affected by DFUs. The current treatments primarily focus on topical treatments, neglecting the underlying metabolic conditions.

Objective

To investigate the wound healing efficacy of the phytoconstituent fisetin, administered orally, in managing DFU in diabetic neuropathic Wistar rats.

Methods

This study investigates the therapeutic potential of a phytoconstituent fisetin, in the management of wound healing in STZ-NAD induced diabetic animal model with surgically induced wounds after indication of neuropathy. Fisetin was administered orally at doses of 5, 10, and 15 mg/kg for 30 days following the induction of foot ulcers, Various parameters were measured, including blood glucose levels, HbA1c, lipid profile, pro-inflammatory cytokines, antioxidant activity, MDA, and histopathological analysis of wound healing.

Results and Discussion

Fisetin, particularly at 15 mg/kg, significantly modulates blood glucose level, HbA1c, lipid profile, and pro-inflammatory cytokines, further enhancing antioxidant activity, while reducing MDA, indicating a reduction in oxidative stress. Histopathological analysis demonstrated enhanced wound healing by increased fibroblast proliferation and collagen formation, as well as restoration of the epithelial layer. Fisetin also exhibited potential in enhancing re-epithelization, enhancing pro-angiogenic markers, diminishing inflammation, and reducing wound size.

Conclusion

Fisetin demonstrates promising potential in managing DFU by modulating metabolic conditions, reducing blood glucose, oxidative stress, and inflammation, and promoting wound healing. Future studies should focus on unraveling the detailed molecular pathways involved in fisetin's action, along with clinical trials to validate its efficacy in DFU patients.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cdr/10.2174/0115733998367395250515130758
2025-06-16
2026-04-17

  • From This Site

    /content/journals/cdr/10.2174/0115733998367395250515130758
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cdr/22/5/CDR-22-5-02.html?itemId=/content/journals/cdr/10.2174/0115733998367395250515130758&mimeType=html&fmt=ahah

References

  1. ChenY. ZhuangJ. YangC. Development of a major amputation prediction model and nomogram in patients with diabetic foot.Postgrad. Med. J.2024100119090891610.1093/postmj/qgae08739005047
     [Google Scholar]
  2. AhsanA. KhanA. FarooqM.A. NaveedM. BaigM.M.F.A. TianW-x. Physiology of endocrine system and related metabolic disorders.Endocrine Disrupting Chemicals-induced Metabolic Disorders and Treatment StrategiesSpringer: Cham202134110.1007/978‑3‑030‑45923‑9_1
     [Google Scholar]
  3. Aguilar-RecarteD. PalomerX. WahliW. Vázquez-CarreraM. The PPARβ/δ-AMPK connection in the treatment of insulin resistance.Int. J. Mol. Sci.20212216855510.3390/ijms2216855534445261
     [Google Scholar]
  4. MauricioD. AlonsoN. GratacòsM. Chronic diabetes complications: the need to move beyond classical concepts.Trends Endocrinol. Metab.202031428729510.1016/j.tem.2020.01.00732033865
     [Google Scholar]
  5. PrimadhiR.A. SeptrinaR. HapsariP. KusumawatiM. Amputation in diabetic foot ulcer: A treatment dilemma.World J. Orthop.202314531231810.5312/wjo.v14.i5.31237304194
     [Google Scholar]
  6. ZakirM. AhujaN. SurkshaM.A. SachdevR. KalariyaY. NasirM. KashifM. ShahzeenF. TayyabA. KhanM.S. JunejoM. Manoj KumarF.N.U. VarrassiG. KumarS. KhatriM. MohamadT. Cardiovascular complications of diabetes: From microvascular to macrovascular pathways.Cureus2023159e4583510.7759/cureus.4583537881393
     [Google Scholar]
  7. TarginoIG SouzaJSO Factors related to the development of ulcers in patients with Diabetes Mellitus.Research Journal: Care is Key Online201684492934
     [Google Scholar]
  8. ChalotraR. GuptaT. ChibS. AmanatM. KumarP. SinghR. Treatment of diabetic complications: do flavonoids holds the keys?Crit. Rev. Food Sci. Nutr.2023202312237435788
     [Google Scholar]
  9. AnY. XuB. WanS. MaX. LongY. XuY. JiangZ. The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovasc. Diabetol.202322123710.1186/s12933‑023‑01965‑737660030
     [Google Scholar]
  10. LinQ. LiK. ChenY. XieJ. WuC. CuiC. DengB. Oxidative stress in diabetic peripheral neuropathy: Pathway and mechanism-based treatment.Mol. Neurobiol.20236084574459410.1007/s12035‑023‑03342‑737115404
     [Google Scholar]
  11. JwadS.M. Al-FatlawiH.Y. Types of diabetes and their effect on the immune system.J Adv Pharm Pract.2022412130
     [Google Scholar]
  12. ChauhanS. ChalotraR. RathiA. SainiM. DeolS. LardM. Current approaches in healing of wounds in diabetes and diabetic foot ulcers.Curr. Bioact. Compd.2023193104121
     [Google Scholar]
  13. DuanY. ZhangK. XuY. RenW. PuF. A promising method for reducing the incidence of diabetic foot ulcers: Regulating foot temperature during walking.Med. Hypotheses202418311126810.1016/j.mehy.2024.111268
     [Google Scholar]
  14. BhararaM. ArmstrongD.G. RiloH.L. MillsJ. Diabetes related amputations: a call to arms to make a difference.Can. J. Diabetes200933325510.1016/S1499‑2671(09)33183‑4
     [Google Scholar]
  15. EverettE. MathioudakisN. Update on management of diabetic foot ulcers.Ann. N. Y. Acad. Sci.20181411115316510.1111/nyas.1356929377202
     [Google Scholar]
  16. DoupisJ. VevesA. Classification, diagnosis, and treatment of diabetic foot ulcers.Wounds200820511712625942412
     [Google Scholar]
  17. GrynkiewiczG. DemchukO.M. New perspectives for fisetin.Front Chem.2019769710.3389/fchem.2019.0069731750288
     [Google Scholar]
  18. PalH.C. PearlmanR.L. AfaqF. Fisetin and Its Role in Chronic Diseases.Adv Exp Med Biol.201692821324410.1007/978‑3‑319‑41334‑1_10
     [Google Scholar]
  19. ChalotraR. DhanawatM. ChauhanS. MujwarS. GuptaS. Evaluation of Iris Kashmiriana Baker plant extracts against nociception and rheumatoid arthritis in experimental rats: A concept proof by in-silico model.J. Ethnopharmacol.202432111749810.1016/j.jep.2023.11749838030021
     [Google Scholar]
  20. YanL.J. The nicotinamide/streptozotocin rodent model of Type 2 diabetes: Renal pathophysiology and redox imbalance features.Biomolecules2022129122510.3390/biom1209122536139064
     [Google Scholar]
  21. GayathriM. KannabiranK. Antidiabetic and ameliorative potential of Ficus bengalensis bark extract in streptozotocin induced diabetic rats.Indian J. Clin. Biochem.200823439440010.1007/s12291‑008‑0087‑223105795
     [Google Scholar]
  22. LiX. Pharmaceutics and new material.Fibroblast Growth Factors.2nd ed LiX. Academic Press202460368510.1016/B978‑0‑443‑15793‑6.00006‑8
     [Google Scholar]
  23. DecosterdI. AllchorneA. WoolfC.J. Progressive tactile hypersensitivity after a peripheral nerve crush: non-noxious mechanical stimulus-induced neuropathic pain.Pain2002100115516210.1016/S0304‑3959(02)00275‑012435468
     [Google Scholar]
  24. JahangirianJ. JannatifarR. HafeziM. AmozegarH. HosseiniR. NasiriN. MohammadiM. Eftekhari-YazdiP. Is there an association between dyslipidemia and the risk of ovarian hyperstimulation syndrome in a population of non-obese polycystic ovary syndrome patients? A cross-sectional study.Int. J. Fertil. Steril.202519219319940200778
     [Google Scholar]
  25. HiranoT. Excess Triglycerides in Very Low-Density Lipoprotein (VLDL) Estimated from VLDL-Cholesterol could be a Useful Biomarker of Metabolic Dysfunction Associated Steatotic Liver Disease in Patients with Type 2 Diabetes.J. Atheroscler. Thromb.202532225326410.5551/jat.6516439231648
     [Google Scholar]
  26. AdeliO.A. Heidari-SoureshjaniS. RostamianS. Azadegan-DehkordiZ. KhaghaniA. Effects and Mechanisms of Fisetin against Ischemia-reperfusion Injuries: A Systematic Review.Curr. Pharm. Biotechnol.202425162138215310.2174/011389201028182124010210541538310454
     [Google Scholar]
  27. CarvalhoM.T.B. Araújo-FilhoH.G. BarretoA.S. Quintans-JúniorL.J. QuintansJ.S.S. BarretoR.S.S. Wound healing properties of flavonoids: A systematic review highlighting the mechanisms of action.Phytomedicine20219015363610.1016/j.phymed.2021.15363634333340
     [Google Scholar]
  28. Wang-FischerY. GaryantesT. Improving the reliability and utility of streptozotocin-induced rat diabetic model.J. Diabetes Res.20182018111410.1155/2018/805407330345315
     [Google Scholar]
  29. LenzenS. The mechanisms of alloxan and streptozotocin-induced diabetes.Diabetologia200851221622610.1007/s00125‑007‑0886‑718087688
     [Google Scholar]
  30. GriebelerM.L. Morey-VargasO.L. BritoJ.P. TsapasA. WangZ. Carranza LeonB.G. PhungO.J. MontoriV.M. MuradM.H. Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis.Ann. Intern. Med.2014161963964910.7326/M14‑051125364885
     [Google Scholar]
  31. MurakamiT. IwanagaT. OgawaY. FujitaY. SatoE. YoshitomiH. SunadaY. NakamuraA. Development of sensory neuropathy in streptozotocin-induced diabetic mice.Brain Behav.201331354110.1002/brb3.11123407314
     [Google Scholar]
  32. YaribeygiH. AtkinS.L. SahebkarA. A review of the molecular mechanisms of hyperglycemia-induced free radical generation leading to oxidative stress.J. Cell. Physiol.201923421300131210.1002/jcp.2716430146696
     [Google Scholar]
  33. HosseiniA. AbdollahiM. Diabetic neuropathy and oxidative stress: therapeutic perspectives.Oxid. Med. Cell. Longev.20132013111510.1155/2013/16803923738033
     [Google Scholar]
  34. BasraR. PapanasN. FarrowF. KarallieddeJ. VasP. Diabetic foot ulcers and cardiac autonomic neuropathy.Clin. Ther.202244232333010.1016/j.clinthera.2021.12.00234974945
     [Google Scholar]
  35. AlamU. RileyD.R. JugdeyR.S. AzmiS. RajbhandariS. D’AoûtK. MalikR.A. Diabetic neuropathy and gait: a review.Diabetes Ther.2017861253126410.1007/s13300‑017‑0295‑y28864841
     [Google Scholar]
  36. AlmeidaD.A.T. BragaC.P. NovelliE.L.B. FernandesA.A.H. Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin.Braz. Arch. Biol. Technol.201255452753610.1590/S1516‑89132012000400007
     [Google Scholar]
  37. Holzer-GeisslerJ.C.J. SchwingenschuhS. ZachariasM. EinsiedlerJ. KainzS. ReiseneggerP. HolecekC. HofmannE. Wolff-WiniskiB. FahrngruberH. BirngruberT. KamolzL.P. KotzbeckP. The impact of prolonged inflammation on wound healing.Biomedicines202210485610.3390/biomedicines1004085635453606
     [Google Scholar]
  38. Mathew-SteinerS.S. RoyS. SenC.K. Collagen in wound healing.Bioengineering (Basel)2021856310.3390/bioengineering805006334064689
     [Google Scholar]
  39. AntikaL.D. DewiR.M. Pharmacological aspects of fisetin.Asian Pac. J. Trop. Biomed.20211111910.4103/2221‑1691.300726
     [Google Scholar]
  40. PutraMI GustiN DutaTF AlinaM QanitaI NaufalMA Vitamin D supplementation improves foot ulcers among diabetic patients: Pooled analysis of randomized controlled trials.Narra X.202313.
     [Google Scholar]
/content/journals/cdr/10.2174/0115733998367395250515130758
Loading
Preclinical Evaluation of Fisetin in the Management of Diabetic Foot Ulcer in Wistar Rats
Curr. Diabetes Rev. 22, E15733998367395 (2026); https://doi.org/10.2174/0115733998367395250515130758
/content/journals/cdr/10.2174/0115733998367395250515130758
/content/journals/cdr/10.2174/0115733998367395250515130758
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Diabetic foot ulcer; fisetin; phytochemical therapy; preclinical study; streptozotocin-induced diabetes; wound healing

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test