Comparison of the Effect of Ethanol Extracts of Phaleria macrocarpa (scheff.Boerl) Fruit and Metformin on the Kidney Function of Hyperglycaemic Rat Models

Authors

  • Eman sutrisna jenderal Soedirman University http://orcid.org/0000-0001-6169-9650
  • Eman Sutrisna jenderal Soedirman University
  • Nur Signa Aini Gumilas Jenderal Soedirman University
  • Mus topa Jenderal Soedirman University
  • Evy Sulistyoningrum Indonesian Islamic University

DOI:

https://doi.org/10.30595/hmj.v3i2.6656

Keywords:

Phaleria macrocarpa (scheff. Boerl) extract, Kidney function, Hyperglycemia, Metformin, Streptozotocin

Abstract

Diabetes mellitus is a disease that often causes diabetic nephropathy complications due to persistent hyperglycaemia. Phaleria macrocarpa (scheff. Boerl)  is one of the plants that has been widely used in the treatment of diabetes mellitus, but its effect on the risk of diabetic nephropathy is still unknown. A dose of 300mg / 200gbb / day is known as an effective dose that can significantly reduce blood sugar levels in diabetic rat. The Streptozotocin Effect (STZ) causes damage to the pancreas and causes hyperglycaemia. This study aims to compare the effect of Phaleria macrocarpa (scheff. Boerl) fruit extracts on urea and creatinine levels as a parameter of kidney function in hyperglycaemic mouse models. The study was carried out experimentally using the post-test only with control group design. Fifteen white rats were divided into 3 groups. All rats were induced with 40 mg / 200gbb of Streptozotocin (STZ) to experience hyperglycaemia. Group I as negative control was given aquades. Group II was given ethanol extract of Phaleria macrocarpa (scheff. Boerl) with a dose of 300 mg / 200gbw / day. Group III was given Metformin at a dose of 150 mg / 200gbw / day. On the 22nd day of treatment, blood specimens were taken for examination of urea and creatinine levels. The research data were statistically analyzed with α <0.05; CI95%. The mean of urea levels in Group I (79.80 ± 25.09 mg / dl), II (76.00 ± 22.59 mg / dl and III (59.60 ± 6.35 mg / dl). Kruskal-Wallis test results showed no significant difference in urea levels between treatment groups (p value = 0.273; CI95%). The mean of creatinine levels in Group I (0.68 ± 0.07 mg / dl), II (0.63 ± 0.14 md / dL) and III (0.98 ± 0.25 mg / dL). One Way Anova and Post hoc test results showed a significant difference in mean creatinine levels between Groups I and III (p = 0.014; 95% CI) and II with III ( p value = 0.006; CI95%). the results of this study can be concluded that the extract of Phaleria macrocarpa (scheff. Boerl) fruit flesh at a dose of 300 mg / 200gbb has better effectiveness than metformin dose 150 mg / 200gbb in repairing the kidney function of hyperglycaemia rats.

Author Biographies

Eman sutrisna, jenderal Soedirman University

DEPARTMENT OF PHARMACOLOGY

Eman Sutrisna, jenderal Soedirman University

Department of Pharmacology

Nur Signa Aini Gumilas, Jenderal Soedirman University

Department of Histology

Mus topa, Jenderal Soedirman University

Department of Physiology

Evy Sulistyoningrum, Indonesian Islamic University

Department of Histology

References

1. Tipping, R.W., Ford, C.E., Pressel, S.L., Folsom, A.R., Chambless, L.E., Selvin, E. et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733): 2215-2222.2. World Health Organization. Global report on diabetes. Geneva: WHO Press. 2016. http://www.who.int/about/licensing/copyright_form/index.html3. Chawla, A., Chawla, R., & Jaggi, S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian Journal of Endocrinology and Metabolism. 2016; 20(4): 546–5514. Ghaisas, M.M., Navghare, V.V., Takawale, A.R., Zope, V.S., & Phanse, M.A. Antidiabetic and Nephroprotective effect of Tectona grandis Linn. In Alloxan Induced Diabetes. Ars. Pharm. 2010; 51(4): 195-2065. Schena, F.P., & Gesualdo, L. Pathogenetic Mechanisms of Diabetic Nephropathy. Journal of American Society Nephrology. 2005; 16:S30–S336. Elmarakby, A.A. & Sullivan, J.C. Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy. Cardiovascular Therapeutics. 2012;30: 49-59.7. Novelli, M., Canistro, D., Martano, M., Funel, N., Sapone, A., Melega, S., et al. Anti-diabetic properties of a non-conventional radical scavanger,as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice. European Journal of Pharmacology. 2014;729:37-44.8. Cade, W.T. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Physical Therapy. 2008;88:1322–1335.9. Banerjee, M. & Vats, P. Reactive Metabolites and Antioxidant Gene Polymorphisms in Type 2 Diabetes Mellitus. Redox Biology, 2014; 2: 170-177.10. Giacco, F., & Brownlee, M. Oxidative stress and diabetic complications. Circ Res. 2010; 107:1058–1070.11. Geraldes, P. & King, G. L. Activation Protein Kinase C Isoform and Its Impact on Diabetic Complications. Circulation Research, 2010; 106(8): 1319-1331.12. Cao, Z., and Cooper, M.E. Pathogenesis of diabetic nephropathy. Journal of Diabetes Investigation. 2011;2 (4): 243-24713. MacIsaac, R.J., Jerums, G., & Ekinci, E.I. Effects of glycaemic management on diabetic kidney disease. World Journal of Diabetes, 2017; 8(5): 172-18614. Lay, M. M., Karsani, S. A., Mohajer, S., Malek, S.N.A. Phytochemical Constituents, Nutritional Values, Phenolics, Flavonols, Flavonoids, Antioxidant, and Citotoxicity Studies on Phaleria macrocarpa (Scheff.) Boerl Fruits. Biomed Central Complementary and Alternative Medicine, 2014;14: 152-164.15. Sugiwati, S., Setiasih, S.,& Afifah, E. Antihyperglycemic Activity of The Mahkota Dewa [Phaleria macrocarpa (Scheff.) Boerl.] Leaf Extracts As An Alpha-Glucosidase Inhibitor. Makara Kesehatan, 2009;13(2): 74-7816. Arjadi, F., & Priyo, S. Regenerasi Sel Pulau Langerhans pada Tikus Putih (Rattus norvegicus) Diabetes yang Diberi Rebusan Daging Mahkota Dewa (Phaleria macrocarp (scheff.) Boerl.). Sains Medika. 2010;2(2) :117-126.17. Kautsari, S., Susatyo, P., & Sulistyoningrum, E. Tinjauan Histologis Pembuluh Darah Tikus Putih (Rattus norvegicus) Diabetes yang Diberi Rebusan Daging Buah Mahkota Dewa (Phaleria macrocarpha (Scheff.) Boerl.). Mandala of Health. 2010; 4(2): 92-96.18. Sulistyoningrum, E. & Setiawati. Phaleria macrocarpa reduces glomerular growth factor expression in alloxan-induced diabetic rats. Universa medicina, 2013; 3(2):71-7919. Ali, R.B., Atangwho, I.J., Kaur, N., Abraika, O.S., Ahmad, M., Mahmud, R., et al. Bioassay-Guided Antidiabetic Study of Phaleria macrocarpa Fruit Extract. Molecules, 2012; 17: 4986-500220. Hendra, R., Ahmad, S., Sukari, A., Shukor, M.Y., Oskoueian, E. Flavonoid Analyses and Antimicrobial Activity of Various Parts of Phaleria macrocarpa (Scheff.) Boerl Fruits. International Journal of Molecular Sciences, 2011;12: 3422-3431.21. Bashir, S. O., Morsy, M.D., Sakr, H.F., El Refaey, H.M., Eid, R. A., Alkhateeb, M. A., et al. Quercetin Ameliorates Diabetic Nephropathy in Rats via Modulation of Renal Na+/K+ ATPase Expression and Oxidative Stress. American Journal of Pharmacology and Toxicology, 2014;9(1): 84-95.22. Sellamuthu, P.S., Muniappan, B.P., Perumal, S.M., Kandasamy, M. Bioassay-Guided Antidiabetic Study of Phaleria macrocarpa Fruit Extract. Journal of Health Sciences, 2008;55(2): 206-21423. ADA (American Diabetes Association). Standards of Medical Care in Diabetes. Diabetes Care, 2015;38(1): 1-99.24. Katzung, B. G. Farmakologi Dasar dan Klinik Edisi 10. Jakarta : EGC. 2012.25. Morales, A. I., Detaille, D., Prieto, M., Puente, A., Briones, E., Are´valo, M., et al. Metformin Prevents Experimental Gentamicin-Induced Nephropathy by A Mitochondria-Dependent Pathway. Kidney International, 2010; 77: 861-869.26. Singh, J. Maceration, Percolation and Infusion Techniques for the Extraction of Medicinal and Aromatic Plants. In: Handa SS, Khanuja SPS, Longo G, Rakesh DD. Extraction Technologies for Medicinal and Aromatic Plants. Italy:International Center For Science and High Technology. 2008;67-8127. Subiyono, M., Martsiningsih, A., & Gabrela, D. Gambaran Kadar Glukosa Darah Metode GOD-PAP (Glucose Oxsidase – Peroxidase Aminoantypirin) Sampel Serum dan Plasma EDTA (Ethylen Diamin Terta Acetat). Jurnal Teknologi Laboratorium, 2016; 5(1):45-48.28. Amartey, N.A.A., Nsiah, K., & Mensah, F.O. Plasma Levels of Uric Acid, Urea and Creatinine in Diabetics Who Visit the Clinical Analysis Laboratory (CAn-Lab) at Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Journal of Clinical and Diagnostic Research. 2015; 9(2): BC05-BC0929. Sihombing, Marice., Sulistyowati, & Tuminah. Perubahan nilai hematologi, biokimia darah, bobot organ dan bobot badan tikus pada umur berbeda. Jurnal Veteriner, 2011;12(1):58-64.30. Giknis, M.L.A., & Clifford, C.B. Clinical Laboratory Parameter for CRL:WI (Han) Rats. Charles River. 2008.31. Eleazu, C.O., Eleazu, K.C., Chukwuma, S., Essien, U.N. Review of Mechanism of Cell Death Resulting from Streptozotocin Challenge in Experimental Animals, Its Practical Use and Potential Risk to Humans. Journal of Diabetes & Metabolic Disorders, 2013; 12(60): 1-7.32. Ohshiro, Y., Lee, Y., & King, G. L. Mechanism of Diabetic Nephropathy: Role of Protein Kinase-C Acivation. Johns Hopkins Advanced Study in Medicine, 2005; 5(1A): 10-1933. Rahmoune, H., Thompson, P. W., Ward, J. M., Smith, C. D., Hong, G., & Brown, J. Glucose Transporters in Human Renal Proximal Tubular Cells Isolated From The Urine of Patients With Non-Insulin-Dependent Diabetes. Diabetes, 2005; 54: 3427-3434

  1. Triastuti, A., Park, H., & Choi, J.W. Phaleria macrocarpa Suppress Nephropathy by Increasing Renal Antioxidant Enzyme Activity in Alloxan-Induced Diabetic Rats. Natural Product Sciences, 2009;15(3):167-172.
35. Oshimi, S., Zaima, K., Matsuno, Y., Hirasawa, Y., Iizuka, T., Studiawan, H., et al. Studies on the constituens from the fruits of Phaleria macrocarpa. Journal National Medicine, 2008; 62:207-210.36. Detaille, D., Guigas, B., Chauvin, C., Batandier, C., Fontaine, E., Wiernsperger, N., et al. Metformin prevents high glucose induced endothelial cell deaths through a mitochondrial permeability transition dependent process. Diabetes, 2005;54:2179-2187.

Downloads

Published

2020-08-31