Pharmacological evaluation of sustained release matrix tablets containing Vaccinium myrtillus leaf dry extract as an alpha-glucosidase inhibitory drug
DOI:
https://doi.org/10.24959/ubphj.18.169Keywords:
Vaccinium myrtillus leaves, herbal extract, matrix tablets, diabetes mellitus, alpha-glucosidase inhibition, hamstersAbstract
Vaccinium myrtillus leaves are the source of natural polyphenols known to improve glycemic control in diabetic conditions through different mechanisms including intestinal a-glucosidase inhibition. In order to increase the effectiveness of V. myrtillus leaf dry extract as a-glucosidase inhibitory drug its sustained release matrix tablets have been developed.
Aim. To carry out the pharmacological evaluation of V. myrtillus leaf dry extract and its sustained release matrix tablets as a-glucosidase inhibitory agents.
Materials and methods. The matrix tablets were prepared by te wet granulation method. Experimental alimentary metabolic syndrome with persistent insulin resistance was induced in Syrian hamsters by feeding them with highly palatable fat- and sugar rich diet for 12 weeks. From the tenth week of the diet feeding, the pathological hamsters were treated with V. myrtillus leaf dry extract, its sustained release matrix tablets and voglibose tablets as a reference drug. At the end of the treatment period an oral maltose loading test with the determination of blood glucose and serum insulin concentration dynamics was performed. Vaccinium myrtillus leaf dry extract (VMLDE) was obtained according to the method developed under the supervision of Dr. O. Koshoviy (Department of Pharmacognosy, National University of Pharmacy, Kharkiv, Ukraine) [13]. The excipients used to manufacture sustained release matrix tablets were hypromellose (HPMC) of grades Methocel K4M and Methocel K100LV (Dow Chemical Company, USA), Eudragit L100 (Evonik, Germany), microcrystalline cellulose (MCC) of a grade Avicel PH101 (FMC BioPolymer, USA), Plasdone S-630 (Ashland Inc., USA) and magnesium stearate (S.D. Fine. Chemicals Ltd., India). The tablets containing 0.2 mg of voglibose (“Voksid” produced by Kusum Pharm LLC, Ukraine), a marketed α-glucose inhibitor, were used as a reference drug in this study. Methods used : preparation of sustained release matrix tablets, induction of metabolic syndrome and experimental design, biochemical tests, statistical analysis.
Results and discussion. By all markers studied in this work the effectiveness of matrix tablets containing V. myrtillus leaf dry extract exceeded that one of the pure extract and statistically significantly did not differ from reference drug.
Conclusions. V. myrtillus leaf dry extract and its matrix tablets possess the antidiabetic action through several mechanisms, including, but not only intestinal a-glucosidase inhibition, therefore they can be considered as promising agents in diabetes and metabolic syndrome treatment.
References
International Diabetes Federation. IDF Diabetes Atlas, 8th ed. (2017).Brussels,Belgium: International Diabetes Federation. Available at: http://www.diabetesatlas.org/resources/2017–atlas.html
Tundis, R., Loizzo, M. R., Menichini, F. (2010). Natural Products as Amylase and Glucosidase Inhibitors and their Hypoglycaemic Potential in the Treatment of Diabetes: An Update. Mini–Reviews in Medicinal Chemistry, 10 (4), 315–331. doi: 10.2174/138955710791331007
Coman, C., Rugina, O. D., Socaciu, C. (2012). Plants and Natural Compounds with Antidiabetic Action. Notulae Botanicae Horti Agrobotanici Cluj–Napoca, 40 (1), 314. doi: 10.15835/nbha4017205
Dragan, S., Andrica, F., Serban, M.–C., Timar, R. (2014). Polyphenols–Rich Natural Products for Treatment of Diabetes. Current Medicinal Chemistry, 22 (1), 14–22. doi: 10.2174/0929867321666140826115422
Kolychev, I.O., Koshovyi, O. M., Zahaiko, A. L., Krasnikova, T. O., Kovalova, A. M. (2016). Farmakom, 1, 67–73.
Meng, S., Cao, J., Feng, Q., Peng, J., Hu, Y. (2013). Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review. Evidence–Based Complementary and Alternative Medicine, 2013, 1–11. doi: 10.1155/2013/801457
Ong, K. W., Hsu, A., Tan, B. K. H. (2013). Anti–diabetic and anti–lipidemic effects of chlorogenic acid are mediated by ampk activation. Biochemical Pharmacology, 85 (9), 1341–1351. doi: 10.1016/j.bcp.2013.02.008
Ruban, E. A., Kolisnyk, T. E., Slipchenko, G. D. (2015). Annals of Mechnikov Institute, 4, 17–24.
Farah, A., Monteiro, M., Donangelo, C. M., Lafay, S. (2008). Chlorogenic Acids from Green Coffee Extract are Highly Bioavailable in Humans. The Journal of Nutrition, 138 (12), 2309–2315. doi: 10.3945/jn.108.095554
Lafay, S., Gil–Izquierdo, A. (2007). Bioavailability of phenolic acids. Phytochemistry Reviews, 7 (2), 301–311. doi: 10.1007/s11101–007–9077–x
Bljajić, K., Petlevski, R., Vujić, L., Čačić, A., Šoštarić, N., Jablan, J., Zovko Končić, M. (2017). Chemical Composition, Antioxidant and α–Glucosidase–Inhibiting Activities of the Aqueous and Hydroethanolic Extracts of Vaccinium myrtillus Leaves. Molecules, 22 (5), 703. doi: 10.3390/molecules22050703
Oboh, G., Agunloye, O. M., Adefegha, S. A., Akinyemi, A. J., Ademiluyi, A. O. (2015). Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): a comparative study. Journal of Basic and Clinical Physiology and Pharmacology, 26 (2). doi: 10.1515/jbcpp–2013–0141
Koshovyi, O. M., Zahaiko, A. L., Kolychev, I.O., Fylymonenko, V. P., Komisarenko, A. M. (2016). Sposib oderzhannia likuvalno–profilaktychnoho zasobu iz hipohlikemichnoiu diieiu z lystia chornytsi zvychainoi. Pat. 111134 Ukraine, MPK A61K 36/45, A61K 31/195, A61K 31/05, A61P 3/10; declared 30.06.2015, published 25.03.2016, № 26.
14. Derzhavna Farmakopeia Ukrainy : v 3 tomakh. (2015). Kharkiv: Ukrainskyi naukovyi farmakopeinyi tsentr yakosti likarskykh zasobiv, 1, 1128.
15. Guide for the Care and Use of Laboratory Animals, 8–th edition. (2011).Washington: The National Academies Press, 246. doi: 10.17226/12910
16. European convention for the protection of vertebrate animals used for experimental and other scientific purposes. (1986).Strasbourg : Council ofEurope, 52.
Dalbøge, L. S., Pedersen, P. J., Hansen, G., Fabricius, K., Hansen, H. B., Jelsing, J., Vrang, N. (2015). A Hamster Model of Diet–Induced Obesity for Preclinical Evaluation of Anti–Obesity, Anti–Diabetic and Lipid Modulating Agents. PLOS ONE, 10 (8), e0135634. doi: 10.1371/journal.pone.0135634
Briand, F., Thiéblemont, Q., Muzotte, E., Sulpice, T. (2012). High–fat and fructose intake induces insulin resistance, dyslipidemia, and liver steatosis and alters in vivo macrophage–to–feces reverse cholesterol transport in hamsters. J Nutr, 142 (4), 704–709. doi: 10.3945/jn.111.153197
Higa, T. S., Spinola, A. V., Fonseca–Alaniz, M. H., Evangelista, F. S. (2014). Comparison between cafeteria and high–fat diets in the induction of metabolic dysfunction in mice. Int J Physiol Pathophysiol Pharmacol, 6 (1), 47–54.
Nair, A., Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal of Basic and Clinical Pharmacy, 7 (2), 27. doi: 10.4103/0976–0105.177703
Downloads
Published
Issue
Section
License
Copyright (c) 2018 National University of Pharmacy
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).