A personalized approach to the treatment and prevention of diabetic foot: molecular mechanisms and the role of taxifolin
- 作者: Seliverstov P.V.1, Zakrevsky V.V.1, Ivaniuk A.S.1, Kerimova A.M.2, Maltsev S.E.3, Tokarev K.M.4
-
隶属关系:
- Federal State Budgetary Educational Institution of Higher Education “S.M. Kirov Military Medical Academy” of the Ministry of Health of the Russian Federation
- Federal State Budgetary Educational Institution of Higher Education «Astrakhan State Medical University» of the Ministry of Healthcare of the Russian Federation
- Orenburg State Medical University (OrSMU)
- Federal State Budgetary Educational Institution of Higher Education “Academician I.P. Pavlov First Saint-Petersburg State Medical University” of the Ministry of Healthcare of Russian Federation
- 期: 卷 23, 编号 6 (2025)
- 页面: 30-40
- 栏目: Original research
- URL: https://ogarev-online.ru/1728-2918/article/view/373744
- DOI: https://doi.org/10.29296/24999490-2025-06-05
- EDN: https://elibrary.ru/eqcncs
- ID: 373744
如何引用文章
详细
Aim. To substantiate the pathogenetic rationale for including aqueous solution of dihydroquercetin (taxifolin) in the comprehensive treatment of diabetic foot and to present the results of a case series on the application of this form in patients with trophic ulcers receiving standard treatment, as well as to compare the obtained results with current data on the molecular mechanisms of taxifolin action.
Methods. A prospective observational study (case series, n = 15) in patients with severe diabetic foot receiving standard therapy supplemented with aqueous dihydroquercetin per os and topically as a gel. The dynamics of ulcer healing (area, depth, granulation), laboratory markers of inflammation and oxidative stress (including malondialdehyde levels), and quality of life according to the SF-36 questionnaire were evaluated. Additionally, to compare the clinical results obtained with global practice, a targeted analysis of publications in PubMed, Scopus, and eLIBRARY databases for 2019–2024 was conducted on the pathogenesis of diabetic foot and the use of taxifolin/dihydroquercetin.
Results. Complete ulcer healing within 6–10 weeks was achieved in 13 out of 15 patients (86.7%), while 2 patients (13.3%) showed a significant reduction in ulcer area (~75%) without complete closure by the end of the observation period. The mean reduction in ulcer area was 68 ± 18%, accompanied by decreased levels of C-reactive protein, malondialdehyde, leptin, and insulin, as well as improved quality of life scores on the SF-36 questionnaire. No adverse events related to the intake of aqueous solution of dihydroquercetin (taxifolin) and topical application of gel formulations based on it were registered. The obtained data are consistent with the concept of the key role of oxidative stress and microangiopathy in the pathogenesis of diabetic foot and indicate the potential of dihydroquercetin as an adjuvant component of comprehensive therapy in comorbid patients.
Conclusion. Based on the presented case series, the integration of aqueous solution of dihydroquercetin (taxifolin) into personalized comprehensive therapy for diabetic foot in comorbid patients appears promising, accelerating ulcer healing with satisfactory tolerability according to observational data; the obtained results are consistent with available experimental and clinical data from global literature, but require confirmation in randomized controlled trials.
作者简介
Pavel Seliverstov
Federal State Budgetary Educational Institution of Higher Education “S.M. Kirov Military Medical Academy” of the Ministry of Health of the Russian Federation
编辑信件的主要联系方式.
Email: seliverstovpv@yandex.ru
ORCID iD: 0000-0001-5623-4226
SPIN 代码: 6166-7005
Candidate of Medical Sciences, Associate Professor, 2nd Department (Advanced Medical Therapy), Responsible for Coordinating Scientific Work at the Department
俄罗斯联邦, Lebedeva St., 6, Saint Petersburg, 194044Victor Zakrevsky
Federal State Budgetary Educational Institution of Higher Education “S.M. Kirov Military Medical Academy” of the Ministry of Health of the Russian Federation
Email: vzakr@list.ru
ORCID iD: 0000-0002-4355-2986
SPIN 代码: 4606-3139
Doctor of Medical Sciences, Professor, Associate Professor, 2nd Department of Advanced Therapy for Physicians
俄罗斯联邦, Lebedeva St., 6, Saint Petersburg, 194044Artem Ivaniuk
Federal State Budgetary Educational Institution of Higher Education “S.M. Kirov Military Medical Academy” of the Ministry of Health of the Russian Federation
Email: oper_hir@mail.ru
ORCID iD: 0009-0005-8622-3655
SPIN 代码: 2960-8188
Candidate of Medical Sciences, Lecturer at the Department of Hospital Surgery
俄罗斯联邦, Lebedeva St., 6, Saint Petersburg, 194044Aida Kerimova
Federal State Budgetary Educational Institution of Higher Education «Astrakhan State Medical University» of the Ministry of Healthcare of the Russian Federation
Email: aika.kerimova02@mail.ru
ORCID iD: 0009-0001-2314-036X
6th Year Student, Medical Degree
俄罗斯联邦, Bakinskaya St., 121, Astrakhan, Astrakhan Region, Southern Federal District, 414000Stanislav Maltsev
Orenburg State Medical University (OrSMU)
Email: pankeev2002@gmail.com
ORCID iD: 0009-0001-2432-7257
6th Year Student
俄罗斯联邦, Sovetskaya Street, 6, Orenburg, Orenburg Region, 460014Kirill Tokarev
Federal State Budgetary Educational Institution of Higher Education “Academician I.P. Pavlov First Saint-Petersburg State Medical University” of the Ministry of Healthcare of Russian Federation
Email: kir.tokarev@mail.ru
ORCID iD: 0009-0005-4505-8841
6th Year Student
俄罗斯联邦, L’va Tolstogo str., 6–8, Saint-Petersburg, 197022参考
- Wang Q., Liu C., An J., Liu J., Wang Y., Cai Y. Mechanisms of microbial infection and wound healing in diabetic foot ulcer: pathogenicity in the inflammatory-proliferative phase, chronicity, and treatment strategies. Front Endocrinol. 2025; 16: 1657928. doi: 10.3389/fendo.2025.1657928
- Armstrong D.G., Tan T.W., Boulton A.J.M., Bus S.A. Diabetic Foot Ulcers: A Review. JAMA. 2023; 330 (1): 62–75. doi: 10.1001/jama.2023.10578
- Santos G.S., Oliveira R.S.S., Rodrigues Y.B., Lima E.S., Carvalho D.R. Global burden of diabetic foot ulcers: a systematic review on prevalence, mortality, and clinical-economic impact. Research, Society and Development. 2025; 14 (7): e3914749222. doi: 10.33448/rsd-v14i7.49222
- Fuentes-Peñaranda Y., Labarta-González-Vallarino A., Arroyo-Bello E., Gómez de Quero Córdoba M. Global Trends in Diabetic Foot Research (2004–2023): A Bibliometric Study Based on the Scopus Database. Int. J. Environ Res Public Health. 2025; 22 (4): 463. doi: 10.3390/ijerph22040463
- Raja J.M., Maturana M.A., Kayali S., Khouzam A., Efeovbokhan N. Diabetic foot ulcer: A comprehensive review of pathophysiology and management modalities. World J. Clin. Cases. 2023; 11 (8): 1684–93. doi: 10.12998/wjcc.v11.i8.1684
- Kim J. The pathophysiology of diabetic foot: a narrative review. J. Yeungnam Med. Sci. 2023; 40 (4): 328–34. doi: 10.12701/jyms.2023.00731
- Silva M.A., Hamilton E.J., Russell D.A., Game F., Wang S.C., Baptista S., Monteiro-Soares M. Diabetic Foot Ulcer Classification Models Using Artificial Intelligence and Machine Learning Techniques: Systematic Review. J. Med. Internet Res. 2025; 27: e69408. doi: 10.2196/69408
- Vuorlaakso M., Kiiski J., Salonen T., Karppelin M., Helminen M., Kaartinen I. Major amputation profoundly increases mortality in patients with diabetic foot infection. Front Surg. 2021; 8: 655902. doi: 10.3389/fsurg.2021.655902
- Costa R.H.R., Cardoso N.A., Procópio R.J., Navarro T.P., Dardik A., de Loiola Cisneros L. Diabetic foot ulcer carries high amputation and mortality rates, particularly in the presence of advanced age, peripheral artery disease and anemia. Diabetes Metab Syndr. 2017; 11 (2): 583–7. doi: 10.1016/j.dsx.2017.04.008
- Zhang W., Chen L., Xiong Y., Panayi A.C., Abududilibaier A., Hu Y., Yu C., Zhou W., Sun Y. еt al. Antioxidant therapy and antioxidant-related bionanomaterials in diabetic wound healing. Front Bioeng Biotechnol. 2021; 9: 707479. doi: 10.3389/fbioe.2021.707479
- Liu Y., Shi X., Tian Y., Zhai S., Liu Y., Xiong Z., Chu S. An insight into novel therapeutic potentials of taxifolin. Front Pharmacol. 2023; 14: 1173855. doi: 10.3389/fphar.2023.1173855
- Taldaev A., Savina A.D., Olicheva V.V., Ivanov S.V., Terekhov R.P., Ilyasov I.R., Zhevlakova A.K., Selivanova I.A. Protective Properties of Spheroidal Taxifolin Form in Streptozotocin-Induced Diabetic Rats. Int. J. Mol. Sci. 2023; 24 (15): 11962. doi: 10.3390/ijms241511962
- Sun X., Chen R.C., Yang Z.H., Sun G.B., Wang M., Ma X.J., Yang L.J., Sun X.B. Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis. Food Chem Toxicol. 2014; 63: 221–32. doi: 10.1016/j.fct.2013.11.013
- Mi Y., Wang J. Effectiveness of personalized continuous care in wound care of patients with diabetic foot ulcers. Front Endocrinol (Lausanne). 2025; 16: 1612047. doi: 10.3389/fendo.2025.1612047
- Shachar T., Yaacobi E., Romem R., Fadila M., Sarrabia G., Saban M., Ohana N. Personalized Approaches to Diabetic Foot Care: The Impact of Ethnic and Socioeconomic Disparities. J. Pers Med. 2025; 15 (4): 133. doi: 10.3390/jpm15040133
- Ardelean A., Balta D.F., Neamtu C., Neamtu A.A., Rosu M., Totolici B. Personalized and predictive strategies for diabetic foot ulcer prevention and therapeutic management: potential improvements through introducing Artificial Intelligence and wearable technology. Med Pharm Rep. 2024; 97 (4): 419–28. doi: 10.15386/mpr-2818
- Wang Y., Ding C., Zhao Y., Zhang J., Ding Q., Zhang S., Wang N., Yang J., Xi S., Zhao T., Zhao C., Liu W. Sodium alginate/poly(vinyl alcohol)/taxifolin nanofiber mat promoting diabetic wound healing by modulating the inflammatory response, angiogenesis, and skin flora. Int. J. Biol. Macromol. 2023; 252: 126530. doi: 10.1016/j.ijbiomac.2023.126530
- Ding Q., Ding C., Liu X., Zheng Y., Zhao Y., Zhang S., Sun S., Peng Z., Liu W. Preparation of nanocomposite membranes loaded with taxifolin liposome and its mechanism of wound healing in diabetic mice. Int. J. Biol. Macromol. 2023; 241: 124537. doi: 10.1016/j.ijbiomac.2023.124537
- Pérez-Zabala E., Basterretxea A., Castro B., Aizpuru A., Arancon J.A., Moreno C., Zubizarreta A., Larizgoitia Z., Ysa A., Lobato M., Larrazabal A. New antioxidant therapy for hard-to-heal neuroischaemic diabetic foot ulcers with deep exposure. J. Wound Care. 2023; 32 (4): 238–46. doi: 10.12968/jowc.2023.32.4.238
- Ding Q., Liu X., Liu X., Chai G., Wang N., Ma S., Zhang L., Zhang S., Yang J. et al. Polyvinyl alcohol/carboxymethyl chitosan-based hydrogels loaded with taxifolin liposomes promote diabetic wound healing by inhibiting inflammation and regulating autophagy. Int. J. Biol. Macromol. 2024; 263 (1): 130226. doi: 10.1016/j.ijbiomac.2024.130226
- Canadian Institute for Health Information. Equity in diabetes care: A focus on lower limb amputation. Ottawa (ON): CIHI; 2024. Available from: https://www.cihi.ca/en/equity-in-diabetes-care-a-focus-on-lower-limb-amputation
- Van Netten J.J., Woodburn J., Bus S.A. The future for diabetic foot ulcer prevention: A paradigm shift from stratified healthcare towards personalized medicine. Diabetes Metab Res Rev. 2020; 36 (1): e3234. doi: 10.1002/dmrr.3234
- Faraji N., Goli R., Choobianzali B., Bahrami S., Sadeghian A., Sepehrnia N., Ghalandari M. Ozone therapy as an alternative method for the treatment of diabetic foot ulcer: a case report. J. Med. Case Rep. 2021; 15 (1): 326. doi: 10.1186/s13256-021-02829-y
- Хундерякова Н.В., Белослудцева Н.В., Хмиль Н.В., Мосенцов А.А., Степанов М.Р., Ананян М.А., Миронова Г.Д. Исследование влияния водорастворимой формы дигидрокверцетина при его введении per os на энергетический обмен в лимфоцитах крови крыс с экспериментальной кардиомиопатией. Вопросы питания. 2021; 90 (6): 50–8. doi: 10.33029/0042-8833-2021-90-6-50-58 [Khunderyakova N.V., Belosludtseva N.V., Khmil N.V., Mosentsov A.A., Stepanov M.R., Ananyan M.A., Mironova G.D. Study of the effect of a water-soluble form of dihydroquercetin administered per os on energy metabolism in blood lymphocytes of rats with experimental cardiomyopathy. Voprosy pitaniya [Problems of Nutrition]. 2021; 90 (6): 50–8. doi: 10.33029/0042-8833-2021-90-6-50-58 (in Russian)]
- Belosludtseva N.V., Uryupina T.A., Pavlik L.L., Khunderyakova N.V., Khmil N.V., Shigaeva M.I., Kharechkina E.S., Krasnikov A.V., Ananyan M.A., Stepanov M.R., Mironova G.D. Structural and functional alterations in heart mitochondria in a rat model of isoprenaline-induced myocardial injury and their correction with water-soluble Taxifolin. Int. J. Mol. Sci. 2024; 25 (21): 11596. doi: 10.3390/ijms252111596
- Varlamova E.G., Uspalenko N.I., Khmil N.V., Shigaeva M.I., Stepanov M.R., Ananyan M.A., Timchenko M.A., Molchanov M.V., Mironova G.D., Turovsky E.A. A Comparative analysis of neuroprotective properties of Taxifolin and its water-soluble form in ischemia of cerebral cortical cells of the mouse. Int. J. Mol. Sci. 2023; 24 (14): 11436. doi: 10.3390/ijms241411436
- Alalykina E.S., Sergeeva T.N., Ananyan M.A., Cherenkov I.A., Sergeev V.G. A Watersoluble form of dihydroquercetin reduces LPS-induced astrogliosis, vascular remodeling, and mRNA VEGF-a levels in the substantia nigra of aged rats. J. Neurosci Neurol Disord. 2024; 8: 014–9. doi: 10.29328/journal.jnnd.1001092
- Gmoshinski I.V., Ananyan M.A., Shipelin V.A., Riger N.A., Trushina E.N., Mustafina O.K., Guseva G.V., Balakina A.S., Kolobanov A.I., Khotimchenko S.A., Ozherelkov D.Yu. Effect of dihydroquercetin supplementation on the toxic properties of nickel nanoparticles in the experiment. Foods and Raw Materials. 2023; 11 (2): 232–42. doi: 10.21603/2308-4057-2023-2-572
- Селивёрстов П.В., Крюков Е.В., Гриневич В.Б. Практическая реализация технологий искусственного интеллекта при проведении профилактического медицинского осмотра. Медицинский совет. 2025; 13: 266–72. doi: 10.21518/ms2025-322 [Seliverstov P.V., Kryukov E.V., Grinevich V.B. Practical implementation of artificial intelligence technologies during preventive medical examination. Meditsinskiy Sovet. 2025; 13: 266–72. doi: 10.21518/ms2025-322 (in Russian)]
补充文件
