Correction by neuroglutam and succicard of age-associated impairments in accelerated aging in rats with diabetes

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.12.1063

Abstract

Introduction: The study aimed to investigate the impact of a long-term diabetic state on the development of accelerated aging and to evaluate the efficacy of therapy with metformin, neuroglutam, and succicard in correcting associated metabolic, behavioral, and molecular impairments.

Materials and Methods: A diabetes model was induced in rats by combined administration of streptozotocin (50 mg/kg) and nicotinamide (110 mg/kg). The total number of animals involved in the experiment was 50 individuals (25 males, 25 females). The animals were divided into 5 groups: intact, control (diabetic), and groups receiving a 4-week course of metformin (400 mg/kg), neuroglutam (26 mg/kg), or succicard (50 mg/kg). A comprehensive assessment was performed, including behavioral tests (open field, elevated cross maze, novel object recognition, forced swimming with a load, rotarod), metabolic status (oral glucose tolerance test, OGTT), and Klotho protein levels (ELISA).

Results: Diabetes induced anxiety-like behavior, cognitive decline, impaired motor coordination, and a significant decrease in Klotho protein levels. Therapy with metformin and succicardsignificantly increased Klotho protein levels and improved metabolic parameters. Neuroglutam exhibited pronounced nootropic and antidepressant-like effects. All drugs demonstrated differential effects on various aspects of behavioral activity.

Conclusion: The study demonstrates the potential of using metformin (400 mg/kg), neuroglutam (26 mg/kg), and succicard (50 mg/kg) to correct the manifestations of accelerated aging in diabetic rats with daily administration for 4 weeks. Metformin and succicard showed the most pronounced geroprotective potential. The results justify further investigation of combination therapy for correcting age-associated impairments.

Graphical Abstract

Keywords:

accelerated aging, GABA derivatives, Klotho protein, diabetes

References

Bagmetova VV, Tyurenkov IV, Malyuzhenko IV, Ganzikova NS (2018) Neuroprotective effects of neuroglutam in brain damage caused by chronic alcohol intoxication. Experimental and Clinical Pharmacology [Eksperimental’naya i Klinicheskaya Farmakologiya] 81(S): 20. [in Russian]

Dao L, Choi S, Freeby M (2023) Type 2 diabetes mellitus and cognitive function: understanding the connections. Current Opinion in Endocrinology, Diabetes, and Obesity 30(1): 7–13. https://doi.org/10.1097/MED.0000000000000783 [PubMed]

Darenskaya MA, Kolesnikova LI, Kolesnikov SI. (2021) Oxidative stress: Pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bulletin of Experimental Biology and Medicine 171(2): 179–189. https://doi.org/10.1007/s10517-021-05191-7 [PubMed] [PMC]

Dove A, Wang J, Huang H, Dunk MM, Sakakibara S, Guitart-Masip M, Papenberg G, Xu W (2024) Diabetes, prediabetes, and brain aging: The role of healthy lifestyle. Diabetes Care 47(10): 1794–1802. https://doi.org/10.2337/dc24-0860 [PubMed] [PMC]

Echouffo-Tcheugui JB, Perreault L, Ji L, Dagogo-Jack S (2023) Diagnosis and management of prediabetes: A Review. JAMA 329(14): 1206–1216. https://doi.org/10.1001/jama.2023.4063[PubMed]

Galiero R, Caturano A, Vetrano E, Beccia D, Brin C, Alfano M, Di Salvo J, Epifani R, Piacevole A, Tagliaferri G, Rocco M, Iadicicco I, Docimo G, Rinaldi L, Sardu C, Salvatore T, Marfella R, Sasso FC (2023) Peripheral neuropathy in diabetes mellitus: pathogenetic mechanisms and diagnostic options. International Journal of Molecular Sciences 24(4): 3554. https://doi.org/10.3390/ijms24043554 [PubMed] [PMC]

Kavalerova DA, Snigur GL, Surin SS, Tyurenkov IN, Bakulin DA, Sakharova EYu (2023) Features of klotho protein expression in rat kidneys in experimental hyperglycemia against the background of pharmacological correction with GABA derivatives. Journal of Anatomy and Histopathology [Zhurnal Anatomii i Ghistopatologhii] 12(4): 38-46. https://doi.org/10.18499/2225-7357-2023-12-4-38-46 [in Russian]

Piskovatska V, Stefanyshyn N, Storey KB, Vaiserman AM, Lushchak O (2019) Metformin as a geroprotector: Experimental and clinical evidence. Biogerontology 20(1): 33–48. https://doi.org/10.1007/s10522-018-9773-5 [PubMed]

Prud'homme GJ, Glinka Y, Kurt M, Liu W, Wang Q (2017) The anti-aging protein Klotho is induced by GABA therapy and exerts protective and stimulatory effects on pancreatic beta cells. Biochemical and Biophysical Research Communications 493(4): 1542–1547. https://doi.org/10.1016/j.bbrc.2017.10.029 [PubMed]

Prud'homme GJ, Kurt M, Wang Q (2022) Pathobiology of the Klotho antiaging protein and therapeutic considerations. Frontiers in Aging 3: 931331. https://doi.org/10.3389/fragi.2022.931331 [PubMed] [PMC]

Sagoo MK, Gnudi L (2020) Diabetic nephropathy: An overview. Methods in Molecular Biology 2067: 3–7. https://doi.org/10.1007/978-1-4939-9841-8_1 [PubMed]

Shen J, Bin W, Lin X, Lai Y, Lin X, Guan T, Liu H (2025) Klotho protein: A multifaceted guardian of healthy aging and its therapeutic potential. International Journal of Nanomedicine 20: 7251–7270. https://doi.org/10.2147/IJN.S514516 [PubMed] [PMC]

Smirnov AV, Tyurenkov IN, Bisinbekova AI, Bakulin DA (2024) Morphofunctional changes in cerebral motor cortex in experimental type I diabetes mellitus. Journal of Anatomy and Histopathology [Zhurnal Anatomii i Ghistopatologhii] 13(2): 46–53. https://doi.org/10.18499/2225-7357-2024-13-2-46-53 [in Russian]

Tyurenkov IN, Bakulin DA, Smirnov AV, Ekova MR, Bisinbekova AI, Snigur GL, Velikorodnaya YuI, Morkovin EI, Verkholyak DV, Vasilyeva OS (2023) Neuroprotective properties of GABA and its derivatives in diabetic encephalopathy in old animals. Pharmacy & Pharmacology 11(3): 211–227. https://doi.org/10.19163/2307-9266-2023-11-3-211-227

Tyurenkov IN, Faibisovich TI, Bakulin DA (2023a) Synergistic effects of GABA and hypoglycemic drugs. Problems of Endocrinology [Problemy Endokrinologii] 69(4): 61–69. https://doi.org/10.14341/probl13257 [in Russian]

Tyurenkov IN, Faibisovich TI, Dubrovina MA, Bakulin DA, Kurkin DV (2023b) Gabaergic system in the regulation of the functioning of pancreas beta-cells in normal physiological conditions and in diabetes. Progress in Physiological Science [Uspekhi Fiziologicheskikh Nauk] 54(2): 86–104. https://doi.org/10.31857/S030117982302008X [in Russian]

Wang Y, Liu H, Zheng M, Yang Y, Ren H, Kong Y, Wang S, Wang J, Jiang Y, Yang J, Shan C (2021) Berberine slows the progression of prediabetes to diabetes in zucker diabetic fatty rats by enhancing intestinal secretion of glucagon-like peptide-2 and improving the gut microbiota. Frontiers in Endocrinology 12: 609134. https://doi.org/10.3389/fendo.2021.609134 [PubMed] [PMC]

Weinberg Sibony R, Segev O, Dor S, Raz I (2024) Overview of oxidative stress and inflammation in diabetes. Journal of Diabetes 16(10): e70014. https://doi.org/10.1111/1753-0407.70014 [PubMed] [PMC]

World Health Organization (WHO). Ageing and ealth https://www.who.int/news-room/fact-sheets/detail/ageing-and-health

Author Contribution

Alexandr A. Pokhlebin, Volgograd State Medical University

Researcher of Laboratory of Pharmacology of Cardiovascular Drugs, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University, Volgograd, Russia; e-mail: a.pokhlebin@gmail.com; ORCID ID: https://orcid.org/0000-0002-0474-5005. The author was responsible for all aspects of the work; analyzing and interpreting the study results; design of the final version of the manuscript.

Nikita S. Bolokhov, Volgograd State Medical University

Researcher of Laboratory of Pharmacology of Cardiovascular Drugs, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University, Volgograd, Russia; e-mail: main@gmail.com; ORCID ID: https://orcid.org/0000-0002-2458-5731. The author was responsible for modeling and control of pathology, design of the final version of the manuscript.

Gennady Yu Balakin, Volgograd State Medical University

Assistant of the Department of Operative Surgery and Topographic Anatomy, Volgograd State Medical University, Volgograd, Russia; e-mail: cobra.balakin@yandex.ru; ORCID ID: https://orcid.org/0009-0003-5333-1399. The author was responsible for conducting behavioral tests and physical performance tests.

Vladislav E. Pustynnikov, Volgograd State Medical University

Researcher of Laboratory of Pharmacology of Cardiovascular Drugs, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University, Volgograd, Russia; e-mail: volgmed@gmail.com; ORCID ID: https://orcid.org/0000-0001-9561-5320. The author was responsible for conducting enzyme immunoassay and interpreting the results.

Olga S. Vasilyeva, Herzen Russian State Pedagogical University

Candidate of Sciences (Chemistry), Senior Researcher, Laboratory of Nitro Compounds, Herzen Russian State Pedagogical University, St. Petersburg, Russia; e-mail: ovasja@gmail.com; ORCID ID:https://orcid.org/0000-0002-0309-1580. The author was responsible for the development of the studied compounds.

Ivan N. Tyurenkov, Volgograd State Medical University

Doctor Habil. of Medical Sciences, Professor, Corresponding member of the Russian Academy of Sciences, Head of the Laboratory of Pharmacology of Cardiovascular Drugs, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University, Volgograd, Russia; e-mail: fibfuv@mail.ru; ORCID ID: https://orcid.org/0000-0001-7574-3923. The author was responsible for the idea and planning of the work structure.

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Published

30-03-2026

How to Cite

Pokhlebin AA, Bolokhov NS, Balakin GY, Pustynnikov VE, Vasilyeva OS, Tyurenkov IN (2026) Correction by neuroglutam and succicard of age-associated impairments in accelerated aging in rats with diabetes. Research Results in Pharmacology 12(1): 101–110. https://doi.org/10.18413/rrpharmacology.12.1063

Issue

Vol. 12 No. 1 (2026)

Section

Experimental Pharmacology

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Copyright (c) 2026 Pokhlebin AA, Bolokhov NS, Balakin GYu, Pustynnikov VE, Vasilyeva OS, Tyurenkov IN

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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