Abstract
Due to substantial morbidity and high complication rate of diabetes mellitus, which is considered as the third killer in the world, a search for the effective blockade of the progression of diabetic nephropathy (DN) remains a therapeutic challenge. Alternative antidiabetic drugs from natural plants are highly demanded nowadays. The aim of this study was to investigate the renoprotective effect of secoisolariciresinol diglucoside (SDG) on DN induced in rats. Diabetes was induced in male Sprague-Dawley rats by a high-fat diet (HFD) and an intraperitoneal 35 mg/kg streptozotocin (STZ) injection. Rats were divided into four groups: normal control rats, diabetic control rats, diabetic rats treated with SDG at 10 mg/kg/day for 4 weeks, and diabetic rats treated with SDG at 20 mg/kg/day for 4 weeks. At the end of the treatment, blood and renal tissue samples were collected for biochemical examination. The results revealed that SDG treatment significantly increased insulin level and decreased blood glucose, fructosamine, creatinine, and blood urea nitrogen levels in diabetic rats. Also, SDG significantly increased renal reduced glutathione, superoxide dismutase and decreased malondialdehyde and nitric oxide levels. In addition, SDG downregulated the renal nuclear factor kappa-B (NF-κB), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) and upregulated renal survivin and B-cell lymphoma-2 (Bcl-2) expressions when compared with untreated diabetic control rats. This study demonstrated, for the first time, the renoprotective effects of SDG in HFD/STZ-induced DN in rats through correction of hyperglycemia; attenuation of oxidative/nitrosative stress markers; downregulation of renal expressions of inflammatory markers NF-κB, TNF-α, and iNOS; along with upregulation of renal expressions of antiapoptotic markers survivin and Bcl-2.
Similar content being viewed by others
References
Adolphe JL, Whiting SJ, Juurlink BH, Thorpe LU, Alcorn J (2010) Health effects with consumption of the flax lignan secoisolariciresinol diglucoside. Br J Nutr 103:929
Ahad A, Ganai AA, Mujeeb M, Siddiqui WA (2014) Ellagic acid, an NF-kappaB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact 219C:64–75
Aktuğ H, Çetintaş VB, Kosova B, Oltulu F, Demiray ŞB, Çavuşoğlu T, Akarca SÖ, Yavaşoğlu A (2012) Dysregulation of nitric oxide synthase activity and Bcl-2 and caspase-3 gene expressions in renal tissue of streptozotocin-induced diabetic rats. Turk J Med Sci 42:830–838
Al-Aboudi A, Afifi FU (2011) Plants used for the treatment of diabetes in Jordan: a review of scientific evidence. Pharm Biol 49:221–239
Anjaneyulu M, Chopra K (2004) Effect of irbesartan on the antioxidant defence system and nitric oxide release in diabetic rat kidney. Am J Nephrol 24:488–496
Aragno M, Mastrocola R, Catalano MG, Brignardello E, Danni O, Boccuzzi G (2004) Oxidative stress impairs skeletal muscle repair in diabetic rats. Diabetes 53:1082–1088
Association AD (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33:S62–S69
Aziz MTA, Wassef MAA, Ahmed HH, Rashed L, Mahfouz S, Aly MI, Hussein RE, Abdelaziz M (2014) The role of bone marrow derived-mesenchymal stem cells in attenuation of kidney function in rats with diabetic nephropathy. Diabetol Metab Syndr 6:34
Barre D, Mizier-Barre K, Stelmach E, Hobson J, Griscti O, Rudiuk A, Muthuthevar D (2012) Flaxseed lignan complex administration in older human Type 2 diabetics manages central obesity and prothrombosis—an invitation to further investigation into polypharmacy reduction. J Nutr Metab 2012
Chaudhari HS, Bhandari U, Khanna G (2013) Embelia ribes extract reduces high fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats. Excli J 12:858–871
Duncan AM, Phipps WR, Kurzer MS (2003) Phyto-oestrogens. Best Pract Res Clin Endocrinol Metab 17:253–271
Fornoni A, Ijaz A, Tejada T, Lenz O (2008) Role of inflammation in diabetic nephropathy. Curr Diabetes Rev 4:10–17
Guijarro C, Egido J (2001) Transcription factor-kappa B (NF-kappa B) and renal disease. Kidney Int 59:415–424
Guo C, Han F, Zhang C, Xiao W, Yang Z (2014) Protective effects of oxymatrine on experimental diabetic nephropathy. Planta Med 80:269–276
Guo C, Zhang C, Li L, Wang Z, Xiao W, Yang Z (2014) Hypoglycemic and hypolipidemic effects of oxymatrine in high-fat diet and streptozotocin-induced diabetic rats. Phytomedicine 15:807–8014
Jang JH, Surh YJ (2003) Potentiation of cellular antioxidant capacity by Bcl-2: implications for its antiapoptotic function. Biochem Pharmacol 66:1371–1379
Kelly KJ, Zhang J, Han L, Wang M, Zhang S, Dominguez JH (2013) Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy. Am J Physiol Renal Physiol 305:F1804–F1812
Knight SF, Imig JD (2007) Obesity, insulin resistance, and renal function. Microcirculation 14:349–362
Ko GJ, Kang YS, Han SY, Lee MH, Song HK, Han KH, Kim HK, Han JY, Cha DR (2008) Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Nephrol Dial Transplant 23:2750–2760
Kuhad A, Chopra K (2009) Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB signaling pathway. Life Sci 84:296–301
Lechler P, Wu X, Bernhardt W, Campean V, Gastiger S, Hackenbeck T, Klanke B, Weidemann A, Warnecke C, Amann K (2007) The tumor gene survivin is highly expressed in adult renal tubular cells: implications for a pathophysiological role in the kidney. Amer J Pathol 171:1483–1498
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408
Mani UV, Mani I, Biswas M, Kumar SN (2011) An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus. J Diet Suppl 8:257–265
Maritim A, Sanders R, Watkins JB (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38
Montgomery HAC, Dymock JF (1961) The determination of nitrite in water. Analyst 86:414–416
Moree SS, Rajesha J (2011) Secoisolariciresinol diglucoside—a phytoestrogen nutraceutical of flaxseed: synthesis and evaluation of antioxidant potency. Free Radicals Antioxid 1:31–38
Moree SS, Kavishankar G, Rajesha J (2013) Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats. Phytomedicine 20:237–245
Prabhakar PK, Prasad R, Ali S, Doble M (2013) Synergistic interaction of ferulic acid with commercial hypoglycemic drugs in streptozotocin induced diabetic rats. Phytomedicine 20:488–494
Prasad K (2002) Suppression of phosphoenolpyruvate carboxykinase gene expression by secoisolariciresinol diglucoside (SDG), a new antidiabetic agent. Inter J Angiol 11:107–109
Prasad K (2013) Secoisolariciresinol diglucoside (SDG) isolated from flaxseed, an alternative to ACE inhibitors in the treatment of hypertension. Int J Angiol 22:235–238
Rajesha J, Murthy KNC, Kumar MK, Madhusudhan B, Ravishankar GA (2006) Antioxidant potentials of flaxseed by in vivo model. J Agric Food Chem 54:3794–3799
Rajesha J, Harish N, Basavaraj M, Shylaja M, Karuna K, Ravishankar G (2008) Antioxidant potential of secoisolariciresinol diglucoside isolated from different fractions of flaxseeds. Seed Sci Biotech 2:83–88
Reed M, Meszaros K, Entes L, Claypool M, Pinkett J, Gadbois T, Reaven G (2000) A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 49:1390–1394
Salimifar M, Fatehi-Hassanabad Z, Fatehi M (2013) A review on natural products for controlling type 2 diabetes with an emphasis on their mechanisms of actions. Curr Diabetes Rev 9:402–411
Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 3:401–410
Schmid H, Boucherot A, Yasuda Y, Henger A, Brunner B, Eichinger F, Nitsche A, Kiss E, Bleich M, Gröne HJ (2006) Modular activation of nuclear factor-κB transcriptional programs in human diabetic nephropathy. Diabetes 55:2993–3003
Selcuk MY, Aygen B, Dogukan A, Tuzcu Z, Akdemir F, Komorowski JR, Atalay M, Sahin K (2012) Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-B pathway in high-fat diet fed and Streptozotocin-induced diabetic rats. Nutr Metab 9:30–36
Sharma S, Kulkarni SK, Chopra K (2006) Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats. Clin Exp Pharmacol Physiol 33:940–945
Si X, Li P, Zhang Y, Lv W, Qi D (2014) Renoprotective effects of olmesartan medoxomil on diabetic nephropathy in streptozotocin-induced diabetes in rats. Biomed Rep 2:24–28
Song Q, An X, Li D, Sodha NR, Boodhwani M, Tian Y, Sellke FW, Li J (2009) Hyperglycemia attenuates angiogenic capability of survivin in endothelial cells. Microvas Res 78:257–264
Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P (2005) Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 52:313–320
Staels B, Fruchart JC (2005) Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 54:2460–2470
Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:537–546
Tavafi M (2013) Diabetic nephropathy and antioxidants. J nephropathol 2:20–27
Wiwanitkit V (2006) Formation of fructosamine in diabetic patients—what are implications in terms of energy exchange. Diabetol Croat 2:35–37
Wu Y, Ouyang JP, Wu K, Wang SS, Wen CY, Xia ZY (2005) Rosiglitazone ameliorates abnormal expression and activity of protein tyrosine phosphatase 1B in the skeletal muscle of fat‐fed, streptozotocin‐treated diabetic rats. Br J Pharmacol 146:234–243
Xie W, Du L (2011) Diabetes is an inflammatory disease: evidence from traditional Chinese medicines. Diabetes Obes Metab 13:289–301
Yamabe N, Yokozawa T, Oya T, Kim M (2006) Therapeutic potential of (−)-epigallocatechin 3-O-gallate on renal damage in diabetic nephropathy model rats. J Pharmacol Exp Ther 319:228–236
Zhang T, Gao J, Jin ZY, Xu XM, Chen HQ (2014) Protective effects of polysaccharides from Lilium lancifolium on streptozotocin-induced diabetic mice. Int J Biol Macromol 65:436–440
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of interest
The author declared no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sherif, I.O. Secoisolariciresinol diglucoside in high-fat diet and streptozotocin-induced diabetic nephropathy in rats: a possible renoprotective effect. J Physiol Biochem 70, 961–969 (2014). https://doi.org/10.1007/s13105-014-0364-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-014-0364-x