Veterinary Research Forum

Vet Res Forum

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Betulinic acid reduces the complications of autoimmune diabetes on the body and kidney through effecting on inflammatory cytokines in C57BL/6 mice

Document Type : Original Article

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

3 Department of Pathobiology, Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran

Abstract

Autoimmune diabetes is one of the most common metabolic diseases with increasing prevalence in the past decades in which pancreatic Langerhans β cells are destroyed and lead to lack of insulin due to increased blood sugar. One of the consequences of diabetes is glomerular disease of the kidney, also called diabetes nephropathy. Different studies have been carried out on the effects of triterpenoids and their medicinal effects on diabetes mellitus. betulinic acid, a pentacyclic triterpenoid of Terpenes, is found in bushes and trees. Its medical effects are also approved by many studies. In this survey, we studied the effect of betulinic acid on diabetic inbred C57BL/6 male mice. They were randomly divided to three groups. Group A: Consisted of healthy mice which received citrate buffer. Group B: Diabetic mice without any treatment and group C: Treated diabetic mice with betulinic acid. The level of blood insulin level, fasting blood glucose, C-peptide, TNF-α, IFN-γ, and IL-1 cytokines were measured and pathologic studies of the kidney were performed. The results showed that betulinic acid could increase insulin and C-peptide, and decrease fasting blood sugar, kidney lesions and TNF-α, IFN-γ, IL-1 in the treated groups. The differences were significant except for IL-1. Betulinic acid through reduction of inflammatory cytokines could have positive effects on inflammatory and autoimmune disease including autoimmune diabetes.

Keywords

References
  1. Rother KI. Diabetes treatment — Bridging the divide. N Engl J Med 2007; 12;356(15):1499-1501.
  2. Nordwall M, Bojestig M, Arnqvist HJ, et al. Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linköping Diabetes Complications Study. Diabetologia 2004; 47(7): 1266-1272.
  3. Ökten A, Kaya G, Karagüzel G, et al. Prevalence of diabetic nephropathy in Turkish children with insulin-dependent diabetes mellitus. Tr J Med Sci 1999; 29: 169-173.
  4. Hovind P, Tarnow L, Rossing K, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 2003; 26(4): 1258-1264.
  5. Razavi Z, Momtaz HE, Sahari S. Frequency of microalbuminuria in type 1 diabetic children. Iran J Pediatr 2009; 19(4), 404-408.
  6. Thomson M, Al-Amin ZM, Al-Qattan KK, et al. Anti-diabetic and hypolipidemic properties of garlic (Allium sativum) in streptozotocin-induced diabetic rats. Int J Diabetes Metab 2007; 15: 108-115.
  7. Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy. Clin Chim Acta 2000; 297(1-2): 135-144.
  8. Kodera Y, Ayabe M, Ogasawara K, et al. Allixin accumulation with long-term storage of garlic. Chem Pharm Bull (Tokyo) 2002; 50(3): 405-407.
  9. Wu YG, Lin H, Qi XM,et al. Prevention of early renal injury by mycophenolate mofetil and its mechanism in experimental diabetes. Int Immunopharmacol 2006; 6(3): 445-453.
  10. Thomas L, Huber AR. Renal function--estimation of glomerular filtration rate. Clin Chem Lab Med 2006; 44(11): 1295-1302.
  11. Sharma S, Kulkarni SK, Chopra K. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 2006; 33(10): 940-945.           
  12. Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017; 8(3): 475-487.
  13. Nicholson LB, Kuchroo VK. Manipulation of the Th1/Th2 balance in autoimmune disease.Curr Opin Immunol 1996; 8(6):837-842.
  14. Xiao J,Li J,Cai L, et al .Cytokines and diabetes research.J Diabetes Res 2014; 2014: 920613. doi:10.1155/ 2014/920613.
  15. Jung ME, Duclos BA. Synthetic approach to analogues of betulinic acid. Tetrahedron 2006; 62(40): 9321-9334.
  16. Alakurtti S, Mäkelä T, Koskimies S, et al. Pharmacological properties of the ubiquitous natural product betulin. Eur J Pharm Sci 2006; 29(1): 1-13.
  17. Yoshizumi K, Hirano K, Ando H, et al. Lupane-type saponins from leaves of acanthopanax sessiliflorus and their inhibitory activity on pancreatic lipase. J Agric Food Chem 2006;54(2):335-341.
  18. Zhang Y-N, Zhang W, Hong D, et al. Oleanolic acid and its derivatives: new inhibitor of protein tyrosine
    phosphatase 1B with cellular activities. Bioorg Med Chem 2008;16(18):8697-8705.
  19. Rahman A, Zareen S, Choudhary MI, et al. alpha-glucosidase inhibitory activity of triterpenoids from Cichorium intybus. J Nat Prod 2008;71(5):910-913.
  20. de Melo CL, Queiroz MGR, Filho ACVA, et al. Betulinic acid, a natural pentacyclic triterpenoid, prevents abdominal fat accumulation in mice fed a high-fat diet. J Agric Food Chem 2009;57(19):8776-8781.
  21. Yoon JJ, Lee YJ, Kim JS, et al. Betulinic acid inhibits high glucose-induced vascular smooth muscle cells proliferation and migration. J Cell Biochem 2010; 111(6):1501- 1511.
  22. Ahangarpour A, Ali-Akbari FR, Mohaghegh SM, et al. Effects of Arctium lappa aqueous extract on lipid profile and hepatic enzyme levels of sucrose-induced metabolic syndrome in female rats. Braz J Pharm Sci 2016;52(3):425-431.
  23. Wang S, Yang Z, Xiong F, et al. Betulinic acid ameliorates experimental diabetic-induced renal inflammation and fibrosis via inhibiting the activation of NF-κB signaling pathway. Mol Cell Endocrinol 2016; 434:135-143.
  24. Castro GAJ, Cazarolli LH, Bretanha LC, et al. The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels. Arch Biochem Biophys 2018;648: 20-26.
  25. Rodríguez-Tovar LE, Nevárez-Garza AM, Trejo-Chávez A, et al. Encephalitozoon cuniculi: Grading the histological lesions in brain, kidney, and liver during primoinfection outbreak in rabbits. J Pathog 2016; 2016: 5768428. doi: 10.1155/2016/5768428.
  26. Lee J, Yee ST, Kim JJ, et al. Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice. Chem Biol Interact 2010;188(3):635-642.
  27. Chia YY, Liong SY, Ton SH, et al. Amelioration of glucose homeostasis by glycyrrhizic acid through gluconeogenesis rate-limiting enzymes. Eur J Pharmacol 2012;677(1-3):197-202.
  28. Kim SJ, Quan HY, Jeong KJ, et al. Beneficial effect of betulinic acid on hyperglycemia via suppression of hepatic glucose production. J Agric Food Chem 2014;62(2):434-442.
  29. Gao D, Li Q, Li Y, et al. Antidiabetic potential of oleanolic acid from Ligustrum lucidum Ait. Can J Physiol Pharmacol 2007;85(11): 1076-1083.
  30. Karthic K, Kirthiram KS, Sadasivam S, et al. Identification of alpha-amylase inhibitors from Syzygium cumini Linn seeds. Indian J Exp Biol 2008; 46(9):677-680.
  31. Kim SD, Nho HJ. Isolation and characterization of alpha-glucosidase inhibitor from the fungus Ganoderma lucidum. J Microbiol 2004;42(3):223-227.
  32. Arzani BirganiG, Ahangarpour A, Khorsandi L, et al. Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model. Braz J Pharm Sci [online] 2018; 54(2): e17171, doi:10.1590/ s2175-97902018000217171.
  33. Tang JJ, Li JG, Qi W, et al. Inhibition of SREBP by a small molecule, betulin, improves hyperlipidemia and insulin resistance and reduces atherosclerotic plaques. Cell Metab 2011; 13(1):44-56.
  34. Xie R, Zhang H , Wang XZ, et al. The protective effect of betulinic acid (BA) diabetic nephropathy on streptozotocin (STZ)-induced diabetic rats. Food Funct 2017;8(1):299-306.
  35. Kim SJ, Quan HY, Jeong KJ, et al. Beneficial effect of betulinic acid on hyperglycemia via suppression of hepatic glucose production.J Agric Food Chem 2014; 62(2): 434-442.
  36. Ahangarpour A, Oroojan AA, Khorsandi L, et al. Preventive effects of betulinic acid on streptozotocin-nicotinamide induced diabetic nephropathy in male mouse. J Nephropathol 2016;5(4):128-133.
  37. Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond) 2013; 124(3):139-152.
  38. Jheng HF, Tsai PJ, Chuang YL, et al. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy. Dis Model Mech 2015;8(10):-1311-1321.
  39. Lingaraju MC, Pathak NN, Begum J, et al. Betulinic acid attenuates renal oxidative stress and inflammation in experimental model of murine polymicrobial sepsis. Eur J Pharm Sci. 2015; 70: 12-21.
  40. Chen T, Mou Y, Tan J, et al. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. Int Immunopharmacol 2015; 25(1), 55-64.
  41. Mora C, Navarro JF. Inflammation and diabetic nephropathy. Current Diabetes Reports 2006; 6, 463-468.
  42. Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19(3): 433-442.
  43. Kolati SR, Kasala ER, Bodduluru LN, et al. BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-κB pathway. Environ Toxicol Pharmacol 2015; 39(2):690-699.
  44. Oliveria Costa JF, Barbosa-Filho JM, de Azeveddo Maia GL, et al. Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia. Int Immunopharmacol 2014; 23(2): 469-474.
  45. Zdzisińska B, Rzeski W, Paduch R, et al. Differential effect of betulin and betulinic acid on cytokine production in human whole blood cell cultures. Pol J Pharmacol 2003; 55(2): 235-238.
  46. Hope SV, Knight BA, Shields BM, et al. Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic. Diabet Med 2016; 33(11): 1554-1558
  47. Kramer CK, Choi H, Zinman B, et al. Glycemic variability in patients with early type 2 diabetes: the impact of improvement in β-cell function. Diabetes Care 2014; 37(4):1116-1123.
  48. Bhatt MP, Lim YC, Hwang JY, et al. C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated trans-glutaminase 2 activation. Diabetes 2013; 62(1):243-253.
  49. Nakagawa-Goto K, Yamada K, Taniguchi M, et al. Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents. Bioorg Med Chem Lett 2009;19(13): 3378-3381.
  50. Cichewicz RH, Kouzi SA. Chemistry, biological activity and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med Res Rev 2004; 24(1): 90-114.
Veterinary Research Forum
Volume 12, Issue 2
June 2021
Pages 203-210
Files
History
  • Receive Date: 06 January 2019
  • Revise Date: 26 May 2019
  • Accept Date: 08 June 2019
Share
How to cite
Statistics