ORIGINAL ARTICLES |
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Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation for the management of insulin resistance: chemical analysis and bioactivity |
Ganna Kravchenko1, Oksana Krasilnikova1, Ain Raal2, Matar Mazen1, Natalia Chaika1, Igor Kireyev1, Andriy Grytsyk3, Oleh Koshovyi1 |
1 National University of Pharmacy, 53 Pushkinska Str., Kharkiv 61002, Ukraine; 2 Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia; 3 Ivano-Frankivsk National Medical University, 2 Halytska Str., Ivano-Frankivsk 76018, Ukraine |
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Abstract Bearberry (Arctostaphylos uva-ursi L.) is a perennial plant of the heather family (Ericaceae). The leaves are dominated by arbutin, phenol carbonic acids flavonoids, saponins, etc. It was previously shown that the bearberry leaves extract reduced blood glucose level in healthy animals under glucose overload, so it need to be studied more detail. The aim of the study was to investigate the chemical composition and the effect of dry alcohol extract from bearberry leaves, which enriched with cysteine, on the rats pancreas under experimental dexamethasone-induced insulin resistance (IR). Arctostaphylos uva-ursi L. leaves extract and its modified cysteine preparation were obtained according to the developed method with 50% ethanol solution. Their phytochemical profile, hypoglycaemic and pancreatic protective effect were investigated. Phenologlycoside (arbutin), phenolic carboxylic acid (gallic acid), 5 flavonoids and 4 hydroxycinnamic acids were identified and quantified in the extracts by HPLC. Present data revealed that bearberry leaves alcoholic dry extract enriched with cysteine has a hypoglycaemic and pancreatic protective effect in treated animals under dexamethasone-induced IR model. Treatment improved hyperglycaemia, insulin resistance and beta cell reduction induced by dexamethasone injections.
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Keywords
Arctostaphylos uva-ursi L.
Extract
Hypoglycaemic activity
Leaves
Phenolic substances
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Fund:The research was funded by the Ministry of Health Care of Ukraine at the expense of the State Budget in the framework#2301020"Scientific and scientific-technical activity in the field of health protection "on the topic" Modern approaches to the creation of new medicines for a correction of metabolic syndrome". |
Corresponding Authors:
Ain Raal,E-mail:ain.raal@ut.ee
E-mail: ain.raal@ut.ee
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Issue Date: 12 October 2022
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1 Harding JL, Pavkov ME, Magliano DJ, et al. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62:3–16. 2 Westman EC. Type 2 diabetes mellitus: a pathophysiologic perspective. Front Nutri. 2021;8:536. 3 Sharma VK, Singh TG. chronic stress and diabetes mellitus: interwoven pathologies. Curr Diabetes Rev. 2020;16(6):546–56. 4 Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133–223. 5 Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: review of the underlying molecular mechanisms. J Cell Physiol. 2019;234:8152–61. 6 Chaudhury A, Duvoor C, Dendi VSR, Kraleti S, Chada A, et al. Clinical review of antidiabetic drugs: implications for Type 2 diabetes mellitus management. Front Endocrinol. 2017;8:6. 7 Padhi S, Nayak AK, Behera A. Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed Pharmacother. 2020;131: 110708. 8 Ayepola OR, Brooks NL, Oguntibeju OO. Oxidative stress and diabetic complications: the role of antioxidant vitamins and flavonoids, chapter 2 book. In: Antioxidant-Antidiabetic Agents and Human Health, 2014. 9 Koshovyi OM, Zagayko AL, Kolychev IO, Akhmedov EYu, Komissarenko AN. Phytochemical study of the dry extract from bilberry leaves. Azerbaijan Pharmaceut Pharmacother J. 2016;16(1):18–23. 10 Zagayko AL, Kolisnyk TY, Chumak OI, Ruban OA, Koshovyi OM. Evaluation of anti-obesity and lipid-lowering properties of vaccinium myrtillus leaves powder extract in a hamster model. J Basic Clin Physiol Pharmacol. 2018;29(6):697–703. 11 Koshovyi O, Granica S, Piwowarski JP, Stremoukhov O, Kostenko Y, Kravchenko G, Krasilnikova O, Zagayko A. Highbush blueberry (Vaccinium corymbosum L.) leaves extract and its modified arginine preparation for the management of metabolic syndrome—chemical analysis and bioactivity in rat model. Nutrients. 2021;13:2870. 12 Bone K, Mills S, Ch. Livingstone principles and practice of phytotherapy. In: Modern Herbal Medicine, 2nd edn. 2013. 13 Kravchenko G, Matar M, Krasilnikova O. Screening of bearberry leaves extracts hypoglycemic effect and study of acute toxicity. Ukrainian Biopharmaceut J. 2018;2(55):13–6. 14 Chaika N, Mazen M, Koshovyi O, et al. Research in phytochemical composition and hypoglycemic activity screening of the dry extracts from bearberry leaves. ScienceRise Pharmaceut Sci. 2021;3(31):42–50. 15 Kravchenko GB, Krasilnikova OA, Matar M. The study of hypoglycemic action of extracts from bearberry leaves under the experimental insulin resistance in rats. Clin Pharm. 2020;24(3):40–6. 16 Chaika N, Koshovyi O, Raal A, et al. Phytochemical profile and pharmacological activity of the dry extract from arctostaphylos uva-ursi leaves modified with phenylalanine. ScienceRise Pharmaceut Sci. 2020;6(28):74–8. 17 Kovalenko VN. Compendium 2020-Medicines. MORION, Kiiv, Ukraine, 2020. 18 Parfenov VA. The use of l-lysine Aescinate in diseases of the central nervous system. Neurol Neuropsychiatry Psychosom. 2011;3:99–104. 19 Koshovyi O, Raal A, Kireyev I, Tryshchuk N, et al. Phytochemical and psychotropic research of motherwort (Leonurus cardiaca L.) modified dry extracts. Plants. 2021;10:230. 20 Liu J, Yong H, Yao X, Hu H, Yu D, Xiao L. Recent advances in phenolic– protein conjugates: synthesis, characterization, biological activities and potential applications. RSC Adv. 2019;9:35825–40. 21 Quan TH, Benjakul S, Sae-Leaw T, Balange AK, Maqsood S. Protein– polyphenol conjugates: antioxidant property, functionalities and their applications. Trends Food Sci Technol. 2019;91:507–17. 22 Wego MT, Kamani SLP, Miaffo D, et al. Protective effects of aqueous extract of Baillonella toxisperma stem bark on dexamethasone-induced insulin resistance in rats. Adv Pharmacol Pharmaceut Sci. 2019;2019:1–6. 23 Burgos-Morón E, Abad-Jiménez Z, Martínez de Marañón A, et al. Relationship between oxidative stress, ER stress, and inflammation in type 2 diabetes: the battle continues. J Clin Med. 2019;8(9):1385. 24 Eguchi N, Vaziri ND, Dafoe DC, Ichii H. The role of oxidative stress in pancreatic β cell dysfunction in diabetes. Int J Mol Sci. 2021;22:1509. 25 Shah S, King EM, Chandrasekhar A, Newton R. Roles for the mitogenactivated protein kinase (MAPK) phosphatase, DUSP1, in feedback control of inflammatory gene expression and repression by dexamethasone. J Biol Chem. 2014;289(19):13667–79. 26 Mazzoli A, Sardi C, Breasson L, Theilig F, Becattini B, Solinas G. JNK1 ablation improves pancreatic β-cell mass and function in db/db diabetic mice without affecting insulin sensitivity and adipose tissue inflammation. FASEB Bioadv. 2020;3(2):94–107. 27 Wei Q, Qi L, Lin H, et al. Pathological mechanisms in diabetes of the exocrine pancreas: what’s known and what’s to know. Front Physiol. 2020;28(11): 570276. 28 Win S, Than TA, Kaplowitz N. The regulation of JNK signalling pathways in cell death through the interplay with mitochondrial SAB and upstream post-translational effects. Int J Mol Sci. 2018;19(11):3657. 29 Salman ZK, Refaat R, Selima E, et al. The combined effect of metformin and l-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Eur J Pharmacol. 2013;714(1–3):448–55. 30 Tang C, Yeung LSN, Koulajian K, et al. Glucose-induced β-cell dysfunction in vivo: evidence for a causal role of C-jun N-terminal kinase pathway. Endocrinology. 2018;159(11):3643–54. 31 Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol. 2019;317(3):420–33. 32 Dobrochaeva DN, Kotov MI, Prokudin YN, Barbarich AI. Key to higher plants of Ukraine. 2nd edn. Science Dumka, Kiev, Ukraine, 1999. 33 State Pharmacopoeia of Ukraine. 2nd edn in 3 vol. SO 《Ukrainian Scientific Pharmacopoeial Center of Drugs Quality》, Kharkiv, Ukraine, 2015. 34 Zabolotnyi O, Zabolotnyi V, Koshevoy N. Oil products moisture measurement using adaptive capacitive instrument measuring transducers, integrated computer technologies in mechanical engineering—2020. Lect Notes Netw Syst. 2021;188:81–91. 35 Zabolotnyi O, Koshevoi M. An effective method of bulk materials moisture measurement using capacitive sensors. J Stored Prod Res. 2020;89: 101733. 36 Koshovyi O, Raal A, Kovaleva A, et al. The phytochemical and chemotaxonomic study of Salvia spp. growing in Ukraine. J Appl Biol Biotech. 2020;8(03):29–36. 37 Kurkin VA, Ryazanova TK, Platonov IA, Pavlova LV. Quantitative determination of arbutin in the leaves of Arctostaphylos uva-ursi (l.) Spreng. Chem Plant Mat. 2015;1:95–100. 38 Krivoruchko E, Markin A, Samoilova V, et al. Research in the chemical composition of the bark of Sorbus aucuparia. Ceska Slov Farm. 2018;67(3):113–5. 39 Raal A, Meos A, Hinrikus T, Heinämäki J, et al. Dragendorff’s reagent: historical perspectives and current status of a versatile reagent introduced over 150 years ago at the University of Dorpat, Tartu, Estonia. Pharmazie. 2020;75:299–306. 40 Gontova T, Ilyinska N, Golembiovska O, et al. Study of the component composition of phenolic compounds obtained from dahlia varieties Ken’s flame herb. Der Pharma Chem. 2016;8(18):455–9. 41 Zagayko AL. Modification of the method of modelling experimental insulin resistance in rats: inform. Letter No. 86-2015, Ukrmedpatentinform about innovations in the health care system, Kyiv, 2015. 42 Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–10. 43 Peg RJ. Determination of conjugated dienes and trienes. In: Current protocols in food analytical chemistry. Wiley: New York, D2.1.1–D2.1.3; 2001. 44 Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67–78. 45 McCord JM, Fridovich I. Superoxide dismutase an enzymic function for Erythrocuprein (Hemocuprein). J Biol Chem. 1969;244(22):6049–55. 46 Hafeman DG, Sunde RA, Hoekstra WG. Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J Nutr. 1974;104(5):580–7. 47 Tenovuo J, Pruitt KM, Mansson-Rahemtulla B, Harrington P, Baldone DC. Products of thiocyanate peroxidation: properties and reaction mechanisms. Biochim Biophys Acta. 1986;870(3):377–84. 48 Miller GL. Protein determination for large numbers of samples anal. Chemistry. 1959;31(5):964–6. 49 Bondarenko VH, Kanivska IY, Paramonova SM. Probability theory and mathematical statistics, Part 1. NTUU “KPI”, Kiiv, Ukraine; 2006. 50 Lapach SM, Chubenko AV, Babich PM. Statistical methods in biomedical research using Excel. MORION, Kiiv, Ukraine, 2000. |
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