Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats

  • Nikhil Khurana Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India
  • Pankaj Sharma Deptt. of Chemistry, University of Delhi, Delhi-110007, India
  • Sunita Bhagat Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India
  • Suman Bala Sharma Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India
DOI https://doi.org/10.22270/jddt.v8i6-s.2080

Abstract

4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid which is a succinamic acid derivative has been synthesized in 3 step reaction with malic acid. Its structure confirmation was done by various techniques like 1H NMR, 13C NMR, & HRMS and is recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study, the effect of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid on plasma glucose, serum insulin, serum lipid profile and lipid peroxidation in streptozotocin–nicotinamide induced type 2 diabetic model was investigated.  4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid was administered orally (20 mg/kg b.w.) to streptozotocin + nicotinamide (STZ + NAD) induced diabetic rats for 28 days. A significant increase in fasting blood glucose levels, HbA1c levels, Serum lipid profile (TG & TC) and in  the levels of Malonaldialdehyde (MDA, end product of lipid peroxidation) was observed in STZ +NAD diabetic rats whereas the levels of high density lipoprotein-cholesterol (HDL-C) and serum insulin levels were significantly decreased  in STZ + NAD induced diabetic rats The effect of 4-((benzyloxy)amino)-2-hydroxy-4-oxobutanoic acid was compared with glibenclamide, a reference drug. Treatment with 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid and glibenclamide resulted in a significant reduction of fasting blood glucose levels with increase in plasma insulin levels in diabetic treated rats. 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid also resulted in a significant improvement in serum lipids and lipid peroxidation products. Our results suggest the potential role of 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid in the management of type-2 diabetes mellitus experimental rats.


Keywords: 4-((benzyloxy) amino)-2-hydroxy-4-oxobutanoic acid, dyslipidemia, streptozotocin induced diabetes, lipid peroxidation

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Author Biographies

Nikhil Khurana, Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Pankaj Sharma, Deptt. of Chemistry, University of Delhi, Delhi-110007, India

Deptt. of Chemistry, University of Delhi, Delhi-110007, India

Sunita Bhagat, Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India

Deptt. of Chemistry, Atma Ram Sanatan Dharma College (Univ. of Delhi), New Delhi, India

Suman Bala Sharma, Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

Deptt. of Biochemistry, University College of Medical Sciences (Univ. of Delhi), Delhi, India

References

1. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Emerging Risk Factors Collaboration. Lancet. 2010; 26(375):2215-2222.
2. Pradeepa R, Deepa R, and Mohan V. Epidemiology of diabetes in India-current perspective and future projections. J Indian Med Assoc. 2002; 100 (3):144-8
3. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, et. al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128:40-50.
4. Peetrson KF, Shulman GI. Etiology of Insulin Resistance. Am J Med. 2006; 119:S106
5. Samuel VT, Shulman GI. Integrating mechanisms for insulin resistance: Common threads and missing links. Cell. 2012; 148(5):852-71
6. Tyalor DA. Botanical supplements: weeding out the health risks. Environmental Health Perspectives. 2004; 112(13):A750-753
7. Sharma B, C. Balomajumder, and P. Roy, Hypoglycemic and hypolipidemic effects of flavonoid rich extract from Eugenia jambolana seeds on streptozotocin induced diabetic rats, Food and Chemical Toxicology. 2008; 46 (7):2376–2383,
8. Ravi K., Sivagnanam K., Subramanian S. Anti-diabetic activity of Eugenia jambolana seed kernels on streptozotocin-induced diabetic rats. J Med Food. 2004; 7(2):187-191.
9. Rizvi S.I., Mishra N. Traditional Indian medicines used for the management of diabetes mellitus. J Diabetes Res. 2013: 712092.
10. Tanwar R.S., Sharma S.B., Singh U.R., et al. Antiatherosclerotic Potential of Active Principle Isolated from Eugenia jambolana in Streptozotocin- Induced Diabetic Rats. Evid Based Complement Alternat Med. 2011; 127641.
11. Sharma, S.B., Nasir A., Prabhu K.M., et al. Antihyperglycemic effect of the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus. J Ethnopharmacol.2006; 104(3):367-373.
12. Taofiq O, Gonzalez-Paramas, Barreiro M, Ferreira I. Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review. Molecules. 2017; 22:281
13. Szkudelski T. Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med (Maywood). 2012; 237(5):481-490.
14. Afifi NA, Ramadan A, El-Kashoury EA, El-Banna HA. Some pharmacological activities of essential oils of certain umbelliferous fruits. Vet Me J Giza. 1994; 42:85-92.
15. Zawalich WS, Zawalich KC: Biochemical mechanisms involved in monomethyl succinate-induced insulin secretion. Endocrinology. 1992; 131:649–654,
16. Ladriere L, Louchami K, Vinamber C, Kadiata MM, Jijakli H, Villanueva Penacarrillo ML et al.: Insulinotropic action of the monoethyl ester of succinic acid. Gen Pharm. 1998; 31:377–383
17. Al-Shamaony L, Al-Khazraji SM, Twaiji IA: Hypoglycemic effect of Artemisia herba alba. II. Effect of a valuable extract on some blood parametes in diabetic animals. J Ethnopharmacol. 1994; 43:167–171
18. Hamadi N, Mansour A, Hassan MH, Khalifi-Touhami F, Badary O. Ameliorative effects of resveratrol on liver injury in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2012; 26:384–392.
19. Mano T, Shinohara R, Nagasaka A, Nakagawa H, Uchimura K, Hayashi R et al.: Scavenging effect of nicorandil on free radicals and lipid peroxide in streptozotocin-induced diabetic rats. Metabolism. 2000; 49:427–431, 2
20. Kwiatkowsha S, Piasecka G, Zieba M, Piotrowski W, Nowak D: Increased serum concentrations of conjugated dienes and malondialdehyde in patients with pulmonary tuberculosis. Respiratory Med. 1999; 93:272–276
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1.
Khurana N, Sharma P, Bhagat S, Sharma SB. Effect of a novel succinamic acid derivative as potential anti-diabetic agent in experimental diabetic rats. JDDT [Internet]. 15Dec.2018 [cited 27Jan.2021];8(6-s):57-2. Available from: http://jddtonline.info/index.php/jddt/article/view/2080
Issue
Vol 8 No 6-s (2018): VOLUME 8, ISSUE 6-s Nov-Dec 2018
Section
Research
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