Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy

Authors

  • Oon Zhi Lim Department of Physiology https://orcid.org/0000-0002-3545-709X
  • Boon Seng Yeoh Department of Physiology https://orcid.org/0000-0002-5766-2270
  • Norsuhana Omar Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
  • Mahaneem Mohamed Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia https://orcid.org/0000-0001-9333-1957
  • Anani Aila Mat Zin Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Ker
  • Rozaziana Ahmad Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

DOI:

https://doi.org/10.1590/s2175-97902022e19652%20

Keywords:

Stingless bee, Propolis, Antioxidant, Diabetic cardiomyopathy, Endogenous secretory receptor for advanced glycation end products, Advanced Glycated End Products

Abstract

Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson’s Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.

Downloads

Download data is not yet available.

References

Ahmed R, Tanvir EM, Hossen M, Afroz R, Ahmmed I, Rumpa NE, et al. Antioxidant properties and cardioprotective mechanism of Malaysian propolis in rats. Evidence-Based Complementary Altern Med. 2017;2017.

Beysel S, Unsal IO, Kizilgul M, Caliskan M, Ucan B, Cakal E. The effects of metformin in type 1 diabetes mellitus. BMC endocrine disorders. 2018 Dec;18(1):1.

Bjornstad P, Schäfer M, Truong U, Cree-Green M, Pyle L, Baumgartner A, et al. Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus: randomized controlled trial. Circulation. 2018 Dec 18;138(25):2895-2907.

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615-1625.

Burlá AK, Lobato NS, Fortes ZB, Oigman W, Neves MF. Cardiac fibrosis and vascular remodeling are attenuated by metformin in obese rats. Int J Cardiol. 2013;165(3):483-487.

Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med. 2013;23(3):266-280.

Close B, Banister K, Baumans V, Bernoth EM, Bromage N, Bunyan J, et al. Recommendations for euthanasia of experimental animals: Part 2. Lab Anim. 1991;31(1):1-32.

Cong W, Ruan D, Xuan Y, Niu C, Tao Y, Wang Y, et al. Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart. J Mol Cell Cardiol. 2015;89(Pt B):314-325.

El-Sadany, D. Antioxidants and hypoglycemic studies on Egyptian propolis and foeniculum vulgare on alloxan induced diabetic rats. Int J Anim Biol. 2016;2(1):1-10.

El-Sayed ES, Abo-Salem OM, Aly HA, Mansour AM. Potential antidiabetic and hypolipidemic effects of propolis extract in streptozotocin-induced diabetic rats. Pak J Pharm Sci. 2009;22(2):168-174.

Gagnon J, Sheppard E, Anini Y. Metformin directly inhibits ghrelin secretion through AMP-activated protein kinase in rat primary gastric cells. Diabetes, Obes Metab. 2013;15(3):276-279.

Gajdosik A, Gajdosikova A, Stefek M, Navarova J, Hozova R. Streptozotocin-induced experimental diabetes in male Wistar rats. Gen Physiol Biophys. 1999;18:54-62.

Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation . 2006;114(6):597-605.

Jalil MA, Kasmuri AR, Hadi H. Stingless bee honey, the natural wound healer: a review. Skin Pharm Physiol. 2017;30(2):66-75.

Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res. 2018;122(4):624-638.

Gugliucci A, Menini T. The axis AGE-RAGE-soluble RAGE and oxidative stress in chronic kidney disease. Oxidative Stress and Inflammation in Non-communicable Diseases- Molecular Mechanisms and Perspectives in Therapeutics. 2014:191-208. Springer, Cham.

Heier M, Margeirsdottir HD, Gaarder M, Stensæth KH, Brunborg C, Torjesen PA, et al. Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow- up study. Cardiovasc Diabetol. 2015;14(1):126.

Ibrahim N., Zakaria AJ, Ismail Z, Mohd KS. Antibacterial and phenolic content of propolis produced by two Malaysian stingless bees, Heterotrigona itama and Geniotrigona thoracica. Int J Pharmacogn Phytochem Res. 2016;8(1):156-161.

Ighodaro OM, Akinloye OA. First line defence antioxidants- superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54(4):287- 293.

Kuropatnicki AK, Szliszka E, Krol W. Historical aspects of propolis research in modern times. Evidence-Based Complementary Altern Med . 2013;2013.

Lijnen P, Petrov V. Induction of cardiac fibrosis by aldosterone. J Mol Cell Cardiol . 2000;32(6):865-879.

Miki T, Yuda S, Kouzu H, Miura T. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Failure Rev. 2013;18(2):149-166.

Mladenov M, Gokik M, Hadzi-Petrushev N, Gjorgoski I, Jankulovski N. The relationship between antioxidant enzymes and lipid peroxidation in senescent rat erythrocytes. Physiol Res. 2015;64(6):891.

Mohan M, Al-Talabany S, McKinnie A, Mordi I, Singh J, et al. A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial. Eur Heart J. 2019;40(41):3409-17.

Nna VU, Bakar AB, Lazin MR, Mohamed M. Antioxidant, anti-inflammatory and synergistic anti-hyperglycemic effects of Malaysian propolis and metformin in streptozotocin- induced diabetic rats. Food Chem Toxicol. 2018;120:305-320.

Pournaghi P, Sadrkhanlou RA, Hasanzadeh S, Foroughi A. An investigation on body weights, blood glucose levels and pituitary-gonadal axis hormones in diabetic and metformin- treated diabetic female rats. Vet Res Forum 2012;3(2):79-84. Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Qinna NA, Badwan AA. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats. Drug Des, Dev Ther. 2015;9:2515.

Samak M, Fatullayev J, Sabashnikov A, Zeriouh M, Schmack B, Farag M, et al. Cardiac hypertrophy: an introduction to molecular and cellular basis. Med Sci Monit Basic Res. 2016;22:75-79.

Sharma V, McNeill JH, Verma S. Diabetic cardiomyopathy: where are we 40 years later?. Can J Cardiol. 2006;22(4):305- 308.

Shimizu I, Minamino T. Physiological and pathological cardiac hypertrophy. J Mol Cell Cardiol . 2016;97:245-262.

Szaleczky E, Prechl J, Feher J, Somogyi A. Alterations in enzymatic antioxidant defence in diabetes mellitus− a rational approach. Postgrad Med J. 1999;75(879):13-17.

Usman UZ, Bakar AB, Zin AA, Mohamed M. LC-MS analysis and effects of Malaysian propolis on insulin, glucagon, pancreas and oxidative stress status in streptozotocin- induced diabetic rats. J Med Biomed Res. 2017;16(1):15-27.

Usman UZ, Bakar AB, Mohamed M. Phytochemical composition and activity against hyperglycemia of Malaysian propolis in diabetic rats. Biomed Res. 2016;27(1):46-51.

Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Hui LI, et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003;370(3):1097-1109.

Zhang YL, Wei JR. 3-Nitrotyrosine, a biomarker for cardiomyocyte apoptosis induced by diabetic cardiomyopathy in a rat model. Mol Med Rep. 2013;8(4):989-994.

Downloads

Published

2022-11-23

Issue

Section

Original Article

How to Cite

Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy. (2022). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e19652

Funding data