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Pharmacological Effect of Curcumin in Combination with Piperine in Nicotinamide-Streptozotocin Induced Diabetic Nephropathy in Male Wistar Rats.



Abstract

Background-Curcumin is one of the principle substances found in the rhizome of Curcuma longa L. Piperine, an alkaloid separated from Piper nigrum L., has bioenhancer property.

Objective- The objective of the present study was to evaluate the nephroprotective activity of curcumin when administered concomitantly with piperine in diabetic rats.

Methods- Male Wistar rats were divided into eight groups viz. vehicle control,  disease control,   glibenclamide (1), glibenclamide + piperine (1+50) , curcumin (50), curcumin+ piperine (50+10), curcumin + piperine (50+30), curcumin + piperine (50+50). Overnight fasted rats were administered nicotinamide (110 mg/kg, i.p.) and 15 min after nicotinamide injection, streptozotocin (65 mg/kg, i.p.) was injected in all groups except group 1. Curcumin and piperine combination was administered as 2% Tween 80 suspension. Curcumin was administered (50 mg/kg) by oral route. Piperine was administered (10, 30, 50 mg/kg) through the oral route in combination with curcumin. Treatment proceeded up to 6 weeks. Biochemical, antioxidant parameters and histopathological studies were carried out at the end of the study.

 Result- Curcumin + piperine (50+50 mg/kg) administration caused a significant decrease in blood glucose, triglyceride, serum creatinine, serum uric acid, urine creatinine, and urine albumin levels. The antioxidant activity of the combination was evident as there was a significant increase in kidney GSH and SOD levels along with significant decrease in MDA. The histopathological study showed reduced damage to kidney in curcumin + piperine (50+50 mg/kg) group.

Conclusion- It is thus concluded that curcumin in combination with piperine showed enhanced nephroprotective activity in diabetic rats.

Keywords: Curcumin diabetic nephropathy kidney piperine.

References

  1. Gao Q, Shen W, Qin W, Zheng C, Zhang M, Zeng C, Wang S, Wang J, Zhu X, Liu Z. Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy. Nephrology Dialysis Transplantation. 2010 18; 25(11):3539-47. https://www.ncbi.nlm.nih.gov/pubmed/20483955
  2. ______________________________________________________________________________
  3. Chen KH, Hung CC, Hsu HH, Jing YH, Yang CW, Chen JK. Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats. Chemico-biological interactions. 2011 15; 190(1):45-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863562/
  4. ______________________________________________________________________________
  5. Yamagishi SI, Matsui T. Advanced glycation end products, oxidative stress and diabetic nephropathy. Oxidative medicine and cellular longevity. 2010; 3(2):101-8. https://www.ncbi.nlm.nih.gov/pubmed/20716934
  6. ______________________________________________________________________________
  7. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The lancet. 1998 12; 352(9131):837-53. https://www.ncbi.nlm.nih.gov/pubmed/9742976
  8. ______________________________________________________________________________
  9. Veerapur VP, Prabhakar KR, Thippeswamy BS, Bansal P, Srinivasan KK, Unnikrishnan MK. Antidiabetic effect of Dodonaea viscosa (L). Lacq. aerial parts in high fructose-fed insulin resistant rats: a mechanism based study.
  10. https://www.ncbi.nlm.nih.gov/pubmed/21341538
  11. ______________________________________________________________________________
  12. Saravanan G, Ponmurugan P. Ameliorative potential of S-allylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes. Experimental and toxicologic pathology. 2012 1; 64 (6):639-44. https://www.semanticscholar.org/paper/Ameliorative-potential-of-S-allylcysteine%3A-effect-Saravanan-Ponmurugan/e349df719e32127c2fc1696237a7efa291f0832d
  13. ______________________________________________________________________________
  14. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. InThe molecular targets and therapeutic uses of curcumin in health and disease 2007 (pp. 1-75). Springer, Boston, MA.
  15. https://www.ncbi.nlm.nih.gov/pubmed/17569205
  16. ______________________________________________________________________________
  17. Sharma S, Kulkarni SK, Chopra K. Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clinical and experimental pharmacology and physiology. 2006; 33(10):940-5.
  18. https://www.ncbi.nlm.nih.gov/pubmed/17002671
  19. ______________________________________________________________________________
  20. Meghana K, Sanjeev G, Ramesh B. Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role. European Journal of Pharmacology. 2007 22; 577(1-3):183-91. https://www.ncbi.nlm.nih.gov/pubmed/17900558
  21. ______________________________________________________________________________
  22. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Molecular pharmaceutics. 2007 14; 4(6):807-18. https://www.ncbi.nlm.nih.gov/pubmed/17999464
  23. ______________________________________________________________________________
  24. Sahebkar A. Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome? Biofactors. 2013; 39(2):197-208. https://www.ncbi.nlm.nih.gov/pubmed/23239418
  25. ______________________________________________________________________________
  26. Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. Journal of Pharmacology and Experimental Therapeutics. 1985 Jan 1; 232(1):258-62. https://www.ncbi.nlm.nih.gov/pubmed/3917507
  27. ______________________________________________________________________________
  28. Reen RK, Roesch SF, Kiefer F, Weibel FJ, Singh, J. Piperine impairs cytochrome PA50 1A1 by direct interaction with the enzyme and not by down regulation of CYP1A1 gene expression in rat hepatoma 5 L Cell. Line. Biochem. Biophys. Research Comm. 1996; 218:562-69. http://dx.doi.org/10.1006/bbrc.1996.0100
  29. ______________________________________________________________________________
  30. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA)-General Subjects. 1979 4; 582(1):67-78. https://www.ncbi.nlm.nih.gov/pubmed/760819
  31. ______________________________________________________________________________
  32. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. Journal of Biological chemistry. 1972 May 25; 247(10):3170-5.
  33. https://www.ncbi.nlm.nih.gov/pubmed/4623845
  34. ______________________________________________________________________________
  35. Slater TF, Sawyer BC. The stimulatory effects of carbon tetrachloride and other halogenoalkanes on peroxidative reactions in rat liver fractions in vitro. General features of the systems used. Biochemical Journal. 1971 Aug 1; 123(5):805-14 https://www.ncbi.nlm.nih.gov/pubmed/4399399.
  36. ______________________________________________________________________________
  37. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. Journal of biological chemistry. 1951; 193:265-75. https://www.ncbi.nlm.nih.gov/pubmed/14907713
  38. ______________________________________________________________________________
  39. Yu W, Wu J, Cai F, Xiang J, Zha W, Fan D, Guo S, Ming Z, Liu C. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PloS one. 2012 14; 7(12):e52013. https://www.ncbi.nlm.nih.gov/pubmed/23251674
  40. ______________________________________________________________________________
  41. Meng B, Li J, Cao H. Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications. Current pharmaceutical design. 2013 1; 19(11):2101-13. https://www.ncbi.nlm.nih.gov/pubmed/23116316
  42. ______________________________________________________________________________
  43. Selvendiran K, Banu SM, Sakthisekaran D. Protective effect of piperine on benzo (a) pyrene-induced lung carcinogenesis in Swiss albino mice. Clinica Chimica Acta. 2004 1;350(1-2):73-8
  44. https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201800086
  45. ______________________________________________________________________________
  46. Darshan S, Doreswamy R. Patented antiinflammatory plant drug development from traditional medicine. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives. 2004; 18(5):343-57.
  47. https://www.ncbi.nlm.nih.gov/pubmed/15173991
  48. ______________________________________________________________________________
  49. Bajad S, Singla AK, Bedi KL. Liquid chromatographic method for determination of piperine in rat plasma: application to pharmacokinetics. Journal of Chromatography B. 2002 Sep 5; 776(2):245-9.
  50. https://www.ncbi.nlm.nih.gov/pubmed/12138007
  51. ______________________________________________________________________________
  52. Khajuria A, Zutshi U, Bedi KL. Permeability characteristics of piperine on oral absorption-an active alkaloid from peppers and a bioavailability enhancer. Indian journal of experimental biology. 1998; 36:46-50.
  53. https://www.ncbi.nlm.nih.gov/pubmed/9536651
  54. ______________________________________________________________________________
  55. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia. 1990 1; 33(8):462-4. https://www.semanticscholar.org/paper/Traditional-plant-treatments-for-diabetes.-Studies-Swanston-Flatt-Day/64f070b3e7ee728bf3f4129ccb685c9069ba5ea6
  56. ______________________________________________________________________________
  57. Shirwaikar A, Rajendran K, Kumar CD, Bodla R. Antidiabetic activity of aqueous leaf extract of Annona squamosa in streptozotocin–nicotinamide type 2 diabetic rats. Journal of ethnopharmacology. 2004 1; 91(1):171-5. https://www.ncbi.nlm.nih.gov/pubmed/15036485
  58. ______________________________________________________________________________
  59. Kiran G, Nandini CD, Ramesh HP, Salimath PV. Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rat’s evaluation of various kidney related parameters. Indian J Exp Biol. 2012; 50:133-140. https://www.ncbi.nlm.nih.gov/pubmed/22670476
  60. ______________________________________________________________________________
  61. Patel S, Shan SR, Goyal KR. Antihyperglycemic antihyperlipidemic and antioxidant effects a dihar a polyherbal ayurvedic formulation in streptozotocin induced diabetic rats. Indian J Exp Biol. 2009; 47:564-70.
  62. https://www.ncbi.nlm.nih.gov/pubmed/19761040
  63. ______________________________________________________________________________
  64. Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis.
  65. ; 47:51-9.https://www.ncbi.nlm.nih.gov/pubmed/16377385
  66. ______________________________________________________________________________
  67. Chen KH, Hung CC, Hsu HH, Jing YH, Yang CW, Chen JK. Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats. Chemico-biological interactions. 2011 Mar 15; 190(1):45-53.
  68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863562/
  69. ______________________________________________________________________________
  70. Ramkumar KM, Ponmanickam P, Velayuthaprabhu S, Archunan G, Rajaguru P. Protective effect of Gymnema montanum against renal damage in experimental diabetic rats. Food and Chemical Toxicology. 2009 1; 47(10):2516-21. https://www.researchgate.net/publication/26680448_Protective_effect_of_Gymnema_montanum_against_renal_damage_in_experimental_diabetic_rats
  71. ______________________________________________________________________________
  72. Grover JK, Vats V, Rathi SS, Dawar R. Traditional Indian anti-diabetic plants attenuate progression of renal damage in streptozotocin induced diabetic mice. Journal of Ethnopharmacology. 2001 1; 76(3):233-8. https://www.ncbi.nlm.nih.gov/pubmed/11448544
  73. ______________________________________________________________________________
  74. Ewis SA, Abdelâ€Rahman MS. Effect of metformin on glutathione and magnesium in normal and streptozotocinâ€induced diabetic rats. Journal of applied toxicology. 1995; 15(5):387-90.
  75. https://www.ncbi.nlm.nih.gov/pubmed/8666722
  76. ______________________________________________________________________________
  77. Loven D, Schedl H, Wilson H, Daabees TT, Stegink LD, Diekus M, Oberley L. Effect of insulin and oral glutathione on glutathione levels and superoxide dismutase activities in organs of rats with streptozocin-induced diabetes. Diabetes. 1986 1; 35(5):503-7. https://www.ncbi.nlm.nih.gov/pubmed/3514329
  78. ______________________________________________________________________________
  79. Sözmen EY, Sözmen B, Delen Y, Onat T. Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control. Archives of medical research. 2001 1; 32(4):283-7.
  80. https://www.ncbi.nlm.nih.gov/pubmed/11440784

How to Cite

Kanzar, A., Bodhankar, S., s, arulmozhi, Ghaisas, M., & Mahadik, K. (2021). Pharmacological Effect of Curcumin in Combination with Piperine in Nicotinamide-Streptozotocin Induced Diabetic Nephropathy in Male Wistar Rats. Diabesity, 7(1). https://doi.org/10.15562/diabesity.2021.61
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