Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes

Author(s): Seyed S. Mortazavi-Jahromi, Shahab Alizadeh, Mohammad H. Javanbakht* and Abbas Mirshafiey*

Volume 20, Issue 3, 2020

Page: [446 - 452] Pages: 7

DOI: 10.2174/1871530319666191016103918

Price: $65

Abstract

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes.

Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR.

Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05).

Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.

Keywords: G2013, Guluronic acid, NSAID, Scavenger receptors, Anti-diabetic, Angio-protective.

« Previous Next »
Graphical Abstract

[1]
Blair, M. Diabetes Mellitus Review. Urol. Nurs., 2016, 36(1), 27-36.
[http://dx.doi.org/10.7257/1053-816X.2016.36.1.27] [PMID: 27093761]
[2]
Rowley, W.R.; Bezold, C.; Arikan, Y.; Byrne, E.; Krohe, S. Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Popul. Health Manag., 2017, 20(1), 6-12.
[http://dx.doi.org/10.1089/pop.2015.0181] [PMID: 27124621]
[3]
Katakami, N. Mechanism of Development of Atherosclerosis and Cardiovascular Disease in Diabetes Mellitus. J. Atheroscler. Thromb., 2018, 25(1), 27-39.
[http://dx.doi.org/10.5551/jat.RV17014] [PMID: 28966336]
[4]
Kramer, C.K.; Leitão, C.B.; Pinto, L.C.; Boza, J.; Silveiro, S.P.; Gross, J.L.; Canani, L.H. Risk factors for micro and macrovascular disease in black and white patients with type 2 diabetes mellitus. Rev Assoc Med Bras (1992), 2009, 55(3), 308-314.
[http://dx.doi.org/10.1590/S0104-42302009000300024]
[5]
Yan, M.; Mehta, J.L.; Zhang, W.; Hu, C. LOX-1, oxidative stress and inflammation: a novel mechanism for diabetic cardiovascular complications. Cardiovasc. Drugs Ther., 2011, 25(5), 451-459.
[http://dx.doi.org/10.1007/s10557-011-6342-4] [PMID: 21993919]
[6]
Chen, M.; Masaki, T.; Sawamura, T. LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. Pharmacol. Ther., 2002, 95(1), 89-100.
[http://dx.doi.org/10.1016/S0163-7258(02)00236-X] [PMID: 12163130]
[7]
Allen, D.A.; Yaqoob, M.M.; Harwood, S.M. Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. J. Nutr. Biochem., 2005, 16(12), 705-713.
[http://dx.doi.org/10.1016/j.jnutbio.2005.06.007] [PMID: 16169208]
[8]
Shi, H.; Mao, X.; Zhong, Y.; Liu, Y.; Zhao, X.; Yu, K.; Zhu, R.; Wei, Y.; Zhu, J.; Sun, H.; Mao, Y.; Zeng, Q.; Lanatoside, C.; Lanatoside, C. Promotes Foam Cell Formation and Atherosclerosis. Sci. Rep., 2016, 6, 20154.
[http://dx.doi.org/10.1038/srep20154] [PMID: 26821916]
[9]
Alizadeh, S.; Mirshafiey, A.; Djalali, M.; Alvandi, E.; Mohammadzadeh Honarvar, N.; Javanbakht, M.H. Vitamin D3 Induces Gene Expression of Ox-LDL Scavenger Receptors in Streptozotocin-Induced Diabetic Rat Aortas: New Insight into the Role of Vitamin D in Diabetic Atherosclerosis. Rep. Biochem. Mol. Biol., 2018, 6(2), 170-177.
[PMID: 29766000]
[10]
Mehta, J.L.; Sanada, N.; Hu, C.P.; Chen, J.; Dandapat, A.; Sugawara, F.; Satoh, H.; Inoue, K.; Kawase, Y.; Jishage, K.; Suzuki, H.; Takeya, M.; Schnackenberg, L.; Beger, R.; Hermonat, P.L.; Thomas, M.; Sawamura, T. Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet. Circ. Res., 2007, 100(11), 1634-1642.
[http://dx.doi.org/10.1161/CIRCRESAHA.107.149724] [PMID: 17478727]
[11]
Zeibig, S.; Li, Z.; Wagner, S.; Holthoff, H.P.; Ungerer, M.; Bültmann, A.; Uhland, K.; Vogelmann, J.; Simmet, T.; Gawaz, M.; Münch, G. Effect of the oxLDL binding protein Fc-CD68 on plaque extension and vulnerability in atherosclerosis. Circ. Res., 2011, 108(6), 695-703.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.240515] [PMID: 21293004]
[12]
Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 2012, 32(9), 2045-2051.
[http://dx.doi.org/10.1161/ATVBAHA.108.179705] [PMID: 22895665]
[13]
Belton, O.; Fitzgerald, D.J. Cyclooxygenase isoforms and atherosclerosis. Expert Rev. Mol. Med., 2003, 5(9), 1-18.
[http://dx.doi.org/10.1017/S1462399403005842] [PMID: 14987412]
[14]
Fosslien, E. Cardiovascular complications of non-steroidal anti-inflammatory drugs. Ann. Clin. Lab. Sci., 2005, 35(4), 347-385.
[PMID: 16254252]
[15]
Ong, C.K.; Lirk, P.; Tan, C.H.; Seymour, R.A. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin. Med. Res., 2007, 5(1), 19-34.
[http://dx.doi.org/10.3121/cmr.2007.698] [PMID: 17456832]
[16]
Nazeri, S.; Khadem Azarian, S.; Fattahi, M.J.; Sedaghat, R.; Tofighi Zavareh, F.; Aghazadeh, Z.; Abdollahi, M.; Mirshafiey, A. Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property. Immunopharmacol. Immunotoxicol., 2017, 39(2), 59-65.
[http://dx.doi.org/10.1080/08923973.2017.1282512] [PMID: 28145788]
[17]
Mirshafiey, A.; Mortazavi-Jahromi, S.S.; Taeb, M.; Cuzzocrea, S.; Esposito, E. Evaluation of the Effect of α-L-Guluronic Acid (G2013) on COX-1, COX-2 Activity and Gene Expression for Introducing this Drug as a Novel NSAID with Immunomodulatory Property. Recent Pat. Inflamm. Allergy Drug Discov., 2018, 12(2), 162-168.
[http://dx.doi.org/10.2174/1872213X12666180607121809] [PMID: 29879894]
[18]
Afraei, S.; Azizi, G.; Zargar, S.J.; Sedaghat, R.; Mirshafiey, A. New therapeutic approach by G2013 in experimental model of multiple sclerosis. Acta Neurol. Belg., 2015, 115(3), 259-266.
[http://dx.doi.org/10.1007/s13760-014-0392-x] [PMID: 25388635]
[19]
Taeb, M.; Mortazavi-Jahromi, S.S.; Jafarzadeh, A.; Mirzaei, M.R.; Mirshafiey, A. An in vitro evaluation of anti-aging effect of guluronic acid (G2013) based on enzymatic oxidative stress gene expression using healthy individuals PBMCs. Biomed. Pharmacother., 2017, 90, 262-267.
[http://dx.doi.org/10.1016/j.biopha.2017.03.066] [PMID: 28364598]
[20]
Mortazavi Jahromi, S.S.; Jamshidi, M.M.; Yousefi, M.; Navabi, S.S.; Motamed, N.; Zavareh, F.T.; Yousefi, M.; Mirshafiey, A. Inhibitory effect of G2013 molecule as a novel immunomodulatory agent, on miR-155 gene expression in HEK-Blue hTLR4 cell line. Eur. J. Inflamm., 2016, 14(2), 86-92.
[http://dx.doi.org/10.1177/1721727X16660093]
[21]
Mortazavi-Jahromi, S.S.; Farazmand, A.; Motamed, N.; Navabi, S.S.; Mirshafiey, A. Effects of guluronic acid (G2013) on SHIP1, SOCS1 induction and related molecules in TLR4 signaling pathway. Int. Immunopharmacol., 2018, 55, 323-329.
[http://dx.doi.org/10.1016/j.intimp.2018.01.003] [PMID: 29310108]
[22]
Khadem Azarian, S.; Akhlaghi, M.; Mahmoudi, M.; Mostafaei, S.; Jamshidi, A.R.; Nazeri, S.; Mirshafiey, A. A randomized clinical trial for the assessment of the efficacy and safety of guluronic acid (G2013) in patients with rheumatoid arthritis. Immunopharmacol. Immunotoxicol., 2019, 41(1), 95-101.
[http://dx.doi.org/10.1080/08923973.2018.1555844] [PMID: 30621471]
[23]
Kisiel, B.; Kruszewski, R.; Juszkiewicz, A.; Kłos, K.; Tłustochowicz, M.; Tłustochowicz, W. Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis. Pak. J. Med. Sci., 2015, 31(5), 1078-1083.
[PMID: 26648990]
[24]
Hulthe, J.; Fagerberg, B. Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR Study). Arterioscler. Thromb. Vasc. Biol., 2002, 22(7), 1162-1167.
[http://dx.doi.org/10.1161/01.ATV.0000021150.63480.CD] [PMID: 12117732]
[25]
Li, J.; Zhang, N.; Ye, B.; Ju, W.; Orser, B.; Fox, J.E.; Wheeler, M.B.; Wang, Q.; Lu, W.Y. Non-steroidal anti-inflammatory drugs increase insulin release from beta cells by inhibiting ATP-sensitive potassium channels. Br. J. Pharmacol., 2007, 151(4), 483-493.
[http://dx.doi.org/10.1038/sj.bjp.0707259] [PMID: 17435793]
[26]
Coe, L.M.; Denison, J.D.; McCabe, L.R. Low dose aspirin therapy decreases blood glucose levels but does not prevent type i diabetes-induced bone loss. Cell. Physiol. Biochem., 2011, 28(5), 923-932.
[http://dx.doi.org/10.1159/000335806] [PMID: 22178944]
[27]
Mork, N.L.; Robertson, R.P. Effects of nonsteroidal antiinflammatory drugs in conventional dosage on glucose homeostasis in patients with diabetes. West. J. Med., 1983, 139(1), 46-49.
[PMID: 6624082]
[28]
Viñals, M.; Bermúdez, I.; Llaverias, G.; Alegret, M.; Sanchez, R.M.; Vázquez-Carrera, M.; Laguna, J.C. Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages. Cardiovasc. Res., 2005, 66(1), 141-149.
[http://dx.doi.org/10.1016/j.cardiores.2004.12.024] [PMID: 15769457]
[29]
Anwar, K.; Voloshyna, I.; Littlefield, M.J.; Carsons, S.E.; Wirkowski, P.A.; Jaber, N.L.; Sohn, A.; Eapen, S.; Reiss, A.B. COX-2 inhibition and inhibition of cytosolic phospholipase A2 increase CD36 expression and foam cell formation in THP-1 cells. Lipids, 2011, 46(2), 131-142.
[http://dx.doi.org/10.1007/s11745-010-3502-4] [PMID: 21181286]
[30]
Voloshyna, I.; Kasselman, L.J.; Carsons, S.E.; Littlefield, M.J.; Gomolin, I.H.; De Leon, J.; Reiss, A.B. COX-2-dependent and independent effects of COX-2 inhibitors and NSAIDs on proatherogenic changes in human monocytes/macrophages. J. Investig. Med., 2017, 65(3), 694-704.
[http://dx.doi.org/10.1136/jim-2016-000259] [PMID: 27940550]

Rights & Permissions Print Cite
Article Metrics
16
2
1
1
© 2024 Bentham Science Publishers | Privacy Policy