Antihyperglycemic effects of the northern berry extracts in the streptozotocin-induced rat model of type II diabetes mellitus
E.А. Krivykh ¹, А.E. Gulyaev ², L.V. Kovalenko ³, Z.T. Shulgau ⁴
¹ Budgetary institution of higher education of Khanty-Mansiysk Autonomous Okrug-Ugra «Khanty-Mansiysk state medical Academy», Khanty-Mansiysk, Russian Federation;
² Private institution «National Laboratory Astana» Nazarbayev University, Nur-Sultan, Republic of Kazakhstan;
³ Budgetary institution of higher education of Khanty-Mansiysk Autonomous Okrug-Yugra «Surgut state University», Surgut, Russian Federation;
⁴ Republican state enterprise «National center of biotechnology», Nur-Sultan, Republic of Kazakhstan
Abstract. The purpose of this study was to study the potential therapeutic properties of water-alcohol extracts of bilberry, blueberries, cowberries, cranberries, on the model of experimental streptozotocin diabetes mellitus. Research material and methods. Wild bilberry, cowberries, cranberries and blueberries collected in the summer and autumn of 2018 in the Surgut district of the Khanty-Mansiysk district of the Tyumen region of the Russian Federation were used to obtain polyphenolic water-alcohol extracts of Northern berries. The extracts were concentrated in a vacuum evaporator to the level of polyphenols in 10 mg / ml. the Rats were injected with polyphenol extracts at the rate of 10 mg / kg (the input volume of 0.2-0.3 ml). Results. The concentration of polyphenols in the samples was studied using a commercial set for determining the concentration of polyphenols «Polyphenols folin-ciocalteu (ENOLOGY line by BioSytems. Spain)», in accordance with the instructions of the reagent manufacturer. The results were expressed in the equivalent of Gallic acid, i.e. mg of Gallic acid/ml of berry extract (mgGAE /ml
Conclusion. A model of type II diabetes mellitus obtained in rats with streptozotocin was used to study the effect of extracts of wild bilberry, cowberries, cranberries and blueberries in North-Western Siberia on the level of glycemia and insulin resistance, lipid metabolism, the level of expression of CRP, IL-6 and TNF-α in the liver and adipose tissue of rats, and histopathological changes in pancreatic tissue were also established. Determined that extracts of bilberry, cowberries, cranberries and blueberry on the model of diabetes reduces the severity of insulin resistance such as Metformin, lower blood glucose levels (except lingonberry extract), reduce the concentration of triglycerides (except cowberries extract), reduces the concentration of LDL (except cranberries and cowberries). The use of blueberry extract on the background of diabetes reduces the expression of inflammatory cytokine genes IL-6, TNF-α and CRP. At the same time, extracts of Northern berries in the blood plasma prevent excessive release of free radicals and increase antioxidant activity. Pathomorphological studies of pancreatic tissue document a lower degree of damage to the Langerhans islets against the background of the introduction of Northern berry extracts.
Keywords: diabetes model, streptozotocin, extracts of a cranberry, cowberry, bilberry, blueberry, glycemia, insulin resistance, triglycerides, LDL oxidative status, pancreas tissue histology
There is no conflict of interest.
Contact details of the corresponding author:
Elena А. Krivykh
KrivyhEA@hmgma.ru
Received 04.03.2020г
For citation:
Krivykh E.А., Gulyaev А.E., Kovalenko L.V., Shulgau Z.T. Antihyperglycemic effects of the northern berry extracts in the streptozotocin-induced rat model of type II diabetes mellitus. URL: http://vestnikural.ru/article/1138. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2020, Vol. 17, no. 3, pp. 193–205. DOI: 10.22138/2500-0918-2020-17-3-193-205 (In Russ)
REFERENCES
1. Zuo L., Prather E.R., Stetskiv M., et al. Inflammaging and Oxidative Stress in Human Diseases. From Molecular Mechanisms to Novel Treatments. Int J Mol Sci. 2019, Sep. 10. Vol.20(18). PII: E4472. DOI: 10.3390/ijms20184472.
2. Jaganjac M., Milkovic L., Gegotek A., Cindric M, Zarkovic K., Skrzydlewska E., Zarkovic N. The relevance of pathophysiological alterations in redox signaling of 4-hydroxynonenal for pharmacological therapies of major stress-associated diseases. Free Radic Biol Med. 2019, Nov. 19. PII: S0891-5849(19)31639-9.
3. Moldogazieva N.T., Mokhosoev I.M., Mel’nikova T.I., Porozov Y.B., Terentiev A.A. Oxidative Stress and Advanced Lipoxidation and Glycation End Products (ALEs and AGEs) in Aging and Age-Related Diseases. Oxid Med Cell Longev. 2019, Aug. 14. 3085756. DOI: 10.1155/2019/3085756.
4. Gheibi S., Kashfi K., Ghasemi A. A. Practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin; Biomed Pharmacother; 2017, Nov; 95: 605-613.
5. Mazo V.K., Sidorova Y.S., Zorin S.N., Kochetkova A.A. Streptozotocin induced diabetes rat models; Vopr Pitan; 2016; 85(4):14-21.
6. Stull A.J. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance; Antioxidants (Basel); 2016, Nov. 29; 5(4). PII: E44.
7. Roopchand D.E., Kuhn P., Rojo L.E., Lila M.A., Raskin I. Blueberry polyphenol-enriched soybean flour reduces hyperglycemia, body weight gain and serum cholesterol in mice; Pharmacol Res; 2013, Feb; 68(1):59-67.
8. Kleinert M., Clemmensen C., Hofmann S.M., et al. Animal models of obesity and diabetes mellitus; Nat Rev Endocrinol; 2018, Mar;14(3):140-162.
9. Bonora E., Moghetti Р., Zancanaro С., et al. Estimates of in vivo insulin action in man: Comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies; J. Clin. Endocrinol. Metab; 1989; 68:374–378.
10. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method; Methods; 2001, Dec; 25(4):402-8.
11. Ito F., Ito H., Suzuki Ch., Yahata T., Ikeda K., Hamaoka K. The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein; Int J Mol Sci; 2017, Feb;18(2):454-462.
12. Różańska D., Regulska-Ilow B. Anthocyanins in prevention of type 2 diabetes. Adv Clin Exp Med. 2018; 27(1):135–142.
13. Lutz T.A. Considering our methods: Methodological issues with rodent models of appetite and obesity research; Physiol Behav; 2018, Aug; 1;192:182-187.
14. Ayoub H.M., McDonald M.R., Sullivan J.A., et al. The Effect of Anthocyanin-Rich Purple Vegetable Diets on Metabolic Syndrome in Obese Zucker Rats; J Med Food; 2017, Dec; 20(12):1240-1249.
15. Scazzocchio B., Varì R., Filesi C., et al. Cyanidin-3-O-b-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes; Diabetes; 2011; 60:2234–2244.
16. Nemes A., Homoki J.R., Kiss R., et al. Effect of Anthocyanin-Rich Tart Cherry Extract on Inflammatory Mediators and Adipokines Involved in Type 2 Diabetes in a High Fat Diet Induced Obesity Mouse Model. Nutrients. 2019, Aug.21; Vol.11(9). PII: E1966. DOI: 10.3390/nu11091966.
17. Skrovankova S., Sumczynski D., Mlcek J., Jurikova T., Sochor J. Bioactive Compounds and Antioxidant Activity in Different Types of Berries; Int J Mol Sci; 2015, Oct.16; 16(10):24673-706.
18. Diaconeasa Z., Iuhas C.I., Ayvaz H., et al. Phytochemical Characterization of Commercial Processed Blueberry, Blackberry, Blackcurrant, Cranberry, and Raspberry and Their Antioxidant Activity. Antioxidants (Basel). 2019, Nov.10. Vol. 8(11). PII: E540. DOI: 10.3390/antiox8110540.
19. Kalt W., Cassidy A., Howard L.R., Krikorian R., Stull A.J., Tremblay F., Zamora-Ros R.Recent Research on the Health Benefits of Blueberries and Their Anthocyanins; Adv Nutr; 2019, Jul.22; PII: nmz065.
20. Salehi B., Ata A., Anil Kumar N., et al. Antidiabetic Potential of Medicinal Plants and Their Active Components; Biomolecules. 2019, Sep.30. Vol. 9(10). PII: E551. DOI: 10.3390/biom9100551.
Authors
Elena А. Krivykh
Budgetary institution of higher education of Khanty-Mansi Autonomous Okrug-Yugra «Khanty-Mansi state medical Academy»
Candidate of medical Sciences, associate Professor, head of the Department of public health and healthcare
Russian Federation, 628011, Tyumenskaya oblast’, Khanty-Mansiyskii avtonomnyi okrug – Yugra, g. Khanty-Mansiisk, ul. Mira, d.40,
KrivyhEA@hmgma.ru
Аleksandr E. Gulyaev
Private institution «National Laboratory Astana» Nazarbayev University
Doctor of medical Sciences, Professor, scientific consultant of RSE «national center of biotechnology»
Republic of Kazakhstan, 010000, Nur-Sultan, Kabanbaj-batyra, d. 5
akin@mail.ru
Lyudmila V. Kovalenko
Budgetary institution of higher education of Khanty-Mansiysk Autonomous Okrug-Yugra «Surgut state University»
Doctor of medical Sciences, Professor, head of the Department of pathophysiology and General pathology, Director of the medical Institute
Russian Federation, 628412, Tyumenskaya oblast’, Khanty-Mansiyskii avtonomnyi okrug – Yugra, g. Surgut, ul. Energetikov, d. 22
medsurdirector@gmail.com
Zarina T. Shulgau
«National center of biotechnologies» of the Republic of Kazakhstan
Candidate of medical Sciences, head of the laboratory of toxicology and pharmacology
Republic of Kazakhstan, 010000, Nur-Sultan, Kurgal’zhinskoe shosse, 13/5
shulgau@biocenter.kz