期刊论文详细信息
Diabetology & Metabolic Syndrome
Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)
Heba M Morsi1  Amira A Hassouna1  Fatma M Taha1  Hanan H Ahmed1  Hanan H Fouad1  Mohamed A Wassef1  Abdulrahman L Al-Malki4  Ameen M Rezq1  Ibrahim N El-Ibrashy3  Mohamed F El-Asmar2  Mohamed T Abdel Aziz1 
[1]Unit of Biochemistry and Molecular Biology, the Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo, Egypt
[2]Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
[3]Internal Medicine Department Faculty of Medicine, Cairo University, Cairo, Egypt
[4]Biochemistry Department, Faculty of Science, King Abdul-Aziz University, Jeddah, Saudi Arabia
关键词: Oxidative stress;    Insulin secretion;    Curcumin;    Heme oxygenase −1;    Diabetes Type 1;   
Others  :  814947
DOI  :  10.1186/1758-5996-4-30
 received in 2012-02-29, accepted in 2012-05-13,  发布年份 2012
PDF
【 摘 要 】

Background

Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions.

Materials and methods

Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation.

Results

NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver.

Conclusion

The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin.

【 授权许可】

   
2012 Abdel Aziz et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140710052046196.pdf 903KB PDF download
Figure 5 . 31KB Image download
Figure 4 . 22KB Image download
Figure 3 . 62KB Image download
Figure 2 . 28KB Image download
Figure 1 . 28KB Image download
【 图 表 】

Figure 1 .

Figure 2 .

Figure 3 .

Figure 4 .

Figure 5 .

【 参考文献 】
  • [1]King H, Aubert R, Herman W: Global burden of diabetes, 1995–2025. Prevalence, numerical estimates and projections. Diabetes Care 1998, 21:1414-1431.
  • [2]Oberly LW: Free radicals and diabetes. Free Radic Biol Med 1988, 5:113-124.
  • [3]Kaneto H, Kajimoto Y, Miyagawa J, Matruoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M: Benefecial effects of antioxidants in diabetes. Possible protection of pancreatic b - cells against glucose toxicity. Diabetes 1999, 48:2398-2406.
  • [4]Abraham NG, Kushida T, McClung J, Weiss M, Quan S, Lafaro R, Darzynkiewicz Z, Wolin M: Heme oxygenase-1 attenuates glucose mediatedcell growth arrest and apoptosis in human microvessel endothelial cells. Circ Res 2003, 93:507-514.
  • [5]Baumgartner-Parzer SM, Wagner L, Pettermann M, Grillari J, Gessl A, Waldhausl W: High-glucose-triggered apoptosis in cultured endothelial cells. Diabetes 1995, 44:1323-1327.
  • [6]Zou MH, Shi C, Cohen RA: High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H2 receptor-mediated apoptosis and adhesion molecular expression in cultured human aortic endothelial cells. Diabetes 2002, 51:198-203.
  • [7]Curcio F, Ceriello A: Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. In Vitro Cell Dev Biol 1992, 28A:787-790.
  • [8]Ceriello A, dello RP, Amstad P, Cerutti P: High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes 1996, 45:471-477.
  • [9]Du X, Stocklauser-Farber K, Rosen P: Generation of reactive oxygen intermediates, activation of NF-_B, and induction of apoptosis inhuman endothelial cells by glucose: role of nitric oxide synthase? Free Radic Biol Med 1999, 27:752-763.
  • [10]Goycheva P, Gadjeva V, Popov B: Oxidative stress and its complications in diabetes mellitus. Trakia Journal of Sciences 2006, 4(Suppl 1):1-8.
  • [11]Deng SL, Chen WF, Yang BZL, Liu ZL: Protective effects of curcumin and its analogues free radical-induced oxidative haemolysis of human red blood cells. Food Chem 2006, 98:112-119.
  • [12]Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB: Bioavailability of Curcumin: Problems and Promises. Mol Pharm 2007, 4(Suppl 6):807-818.
  • [13]Otterbein LE, Choi AM: Heme oxygenase: colors of defense against cellular Stress. Am J Physiol Lung Cell Mol Physiol 2000, 279:L1029-L1037.
  • [14]Ndisang JF, Jadhav A: Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes. Am J Physiol 2009, 296(Suppl 4):E829-E841.
  • [15]Ndisang JF, Jadhav A: The heme oxygenase system attenuates pancreatic lesions and improves insulin sensitivity and glucose metabolism in deoxycorticosterone acetate hypertension. Am J Physiol 2010, 298(Suppl 1):R211-R223.
  • [16]Maines MD: The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997, 37:517-554.
  • [17]Piantadosi CA: Biological chemistry of carbon monoxide. Antioxid Redox Signal 2002, 4(Suppl 2):259-270.
  • [18]Mosén H, Salehi A, Henningsson R, Lundquist I: Nitric oxide inhibits, and carbon monoxide activates, islets acid α-glucoside hydrolase activities in parallel with glucose stimulated insulin secretion. J Endocrinol 2006, 190(Suppl 3):681-693.
  • [19]Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R: Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 2002, 61:554-561.
  • [20]Motterlini R, Foresti R, Bassi R, Green CJ: Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000, 28:1303-1312.
  • [21]Trinder P: Determination of blood glucose using an oxidase peroxidase system with a non – carcinogenic chromogen. J Clin Pathol 1969, 22:158-161.
  • [22]Olsson R, Carisson PO: Better vascular engraftment and function in pancreatic islets transplanted without prior culture. Diabetologia 2005, 48:469-476.
  • [23]Bucolo G, David H: Quantitative determination of serum triglycerides by use of enzymes. Clin Chem 1973, 19(Suppl 5):476-482.
  • [24]Burstein M, Scholnick HR, Morfin R: Rapid method for the isolation of lipoproteins from human serum by precipitation by polyanions. J Lipid Res 1970, 11:583-585.
  • [25]Richmond W: Preparation and Properties of a Cholesterol Oxidase from Nocardia sp. and Its Application to the Enzymatic Assay of Total Cholesterol in Serum. Clin Chem 1973, 19:1350-1356.
  • [26]Satoh K: Serum Lipid Peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978, 90:37-43.
  • [27]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 1951, 193:265-275.
  • [28]Abraham NG, Lin JH, Schwartzman ML, Levere RD, Shibahara S: The physiological significance of heme oxygenase. Int J Biochem 1988, 20:543-558.
  • [29]Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 1979, 18(Suppl 24):5294-5299.
  • [30]Miller K, Storts D: PCR Access! A sensitive single-tube two-enzyme system for RT-PCR. Promega Notes 1995, 53:2-5.
  • [31]Lukita-Atmadja W, Ito Y, Baker GL, McCuskey RS: Effect of curcuminoids as anti-inflammatory agents on the hepatic microvascular response to endotoxin. Shock 2002, 17:399-403.
  • [32]Fujisawa S, Atsumi T, Ishihara M, Kadoma Y: Cytotoxicity, ROS-generation activity and radical scavenging activity of curcumin and related compounds. Anticancer Res 2004, 24:563-569.
  • [33]Aggar1wal B, Kumar A, Bharti A: Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 2003, 23:363-398.
  • [34]Pari L, Murugan P: Effect of tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. J Basic Clin Physiol Pharmacol 2005, 16:257-274.
  • [35]Seo KI, Choi MS, Jung UN, Kim HJ, Yeo J, Jeon SM, Lee MK: Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 2008, 52(Suppl 9):995-1004.
  • [36]Rungseesantivanon S, Thenchaisri N, Ruangvejvorachai P, Patumraj S: Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition. BMC Complement Alternat Med 2010, 10:57-65. BioMed Central Full Text
  • [37]Wickenberg J, Ingemansson SL, Hlebowicz J: Effects of Curcuma longa (turmeric) on postprandial plasma glucose and insulin in healthy subjects. Nutr J 2010, 9:43-47. BioMed Central Full Text
  • [38]El-Azab MF, Attia FM, El-Mowafy AM: Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: Effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines. Eur J Pharmacol 2011, 658(Suppl 1):41-48.
  • [39]Best L, Elliott AC, Brown PD: Curcumin induces electrical activity in rat pancreatic beta-cells by activating the volume-regulated anion channel. Biochem Pharmacol 2007, 73:1768-1775.
  • [40]Kanitkar M, Bhonde RR: Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation. Life Sci 2008, 82:182-189.
  • [41]Abdel Aziz MT, El-Asmar MF, El Nadi EG, Wassef MA, Ahmed HH, Rashed LA, Obaia EM, Sabry D, Hassouna AA, Abdel Aziz AT: The Effect of Curcumin on Insulin Release in Rat- Isolated Pancreatic Islets. Angiology 2010, 61(Suppl 6):557-566.
  • [42]Pugazhenthi S, Akhov L, Selvaraj G, Wang M, Alam J: Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells. Am J Physiol Endocrinol Metab 2007, 293:E645-E655.
  • [43]Kim M, Kim Y: Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr Res Pract 2010, 4(Suppl 3):191-195.
  • [44]Donnini D, Zambito AM, Perella G: Glucose may induce cell death through a free radical-mediated mechanism. Biochem Biophys Res Commun 1996, 219:412-417.
  • [45]Baynes JW: Role of oxidative stress in development of complications in diabetes. Diabetes 1991, 40:405-412.
  • [46]Lyons TJ: Oxidized low-density lipoproteins, a role in the pathogenesis of atherosclerosis in diabetes. Diabet Med 1991, 8:411-419.
  • [47]Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL: Neonatal streptozotocin-induced rat model of Type 2 diabetes mellitus: A glance. Indian J Pharmacol 2004, 36(Suppl 4):217-221.
  • [48]Jain SK, Kannan K, Lim G: Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells. Free Radic Biol Med 1998, 25:1083-1088.
  • [49]Jain SK, McVie R: Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients. Diabetes 1999, 48:1850-1855.
  • [50]Suryanarayana P, Satyanarayana A, Balakrishna N, Kumar PU, Reddy GB: Effect of turmeric and curcumin on oxidative stress and antioxidant enzymes in streptozotocin-induced diabetic rat. Med Sci Monit 2007, 13:BR286-BR292.
  • [51]Osawa T, Kato Y: Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci 2005, 1043:440-451.
  • [52]Jain SK, Rains J, Jones K: Effect of curcumin on protein glycosylation, lipid peroxidation, and oxygen radical generation in human red blood cells exposed to high glucose levels. Free Radic Biol Med 2006, 41:92-96.
  • [53]Abraham NG, Rezzani R, Rodella L, Kruger A, Taller D: Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes. Am J Physiol Heart Circ Physiol 2004, 287:H2468-H2477.
  文献评价指标  
  下载次数:20次 浏览次数:7次