Skip to main content
Log in

Effect of iridoid glucoside on plasma lipid profile, tissue fatty acid changes, inflammatory cytokines, and GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The present study was designed to examine the antihyperlipidaemic potential of iridoid glucoside isolated from Vitex negundo leaves in STZ-induced diabetic rats. The levels of cholesterol (TC), triglycerides, lipoproteins, free fatty acids, phospholipids, fatty acid composition, proinflammatory cytokines, muscle glycogen content, and glucose transporter 4 (GLUT4) expression were estimated in control and diabetic rats. Oral administration of iridoid glucoside at a dose of 50 mg/kg body weight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids, and phospholipids. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low density lipoprotein- and very low density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with iridoid glucoside. The fatty acid composition of the liver and kidney was analyzed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was also restored upon treatment with iridoid glucoside. Moreover, the elevated plasma levels of proinflammatory cytokines and decreased levels of muscle glycogen and GLUT4 expression in the skeletal muscle of diabetic rats were reinstated to their normal levels via enhanced secretion of insulin from the remnant β cells of pancreas by the administration of iridoid glucoside. The effect produced by iridoid glucoside on various parameters was comparable with that of glibenclamide, a well-known antihyperglycemic drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Scheen JA (1997) Drug treatment of non-insulin dependent diabetes mellitus in the 1990. Achievement and future development. Drug 54:355–368

    Article  CAS  Google Scholar 

  2. Mohan V, Madan Z, Jha R, Deepa R, Pradeepa R (2004) Diabetes—social and economic perspectives in the new millennium. Int J Diab Dev Countries 24:29–35

    Google Scholar 

  3. King H, Aubert R, Herman WH (1998) Global burden of diabetes 1995–2025. Diabetes Care 21:1414–1431

    Article  CAS  PubMed  Google Scholar 

  4. Maghrani M, Lemhadri A, Zeggwagh NA, El Amraoui M, Haloui M, Jouad H, Eddouks M (2004) Effects of an aqueous extract of Triticum repens on lipid metabolism in normal and recent-onset diabetic rats. J Ethnopharmacol 90:331–337

    Article  CAS  PubMed  Google Scholar 

  5. Manninen V, Tenkanen L, Koskinien P (1992) Joint effects of serum triglycerides and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki heart study: implications for treatment. Circulation 85:37–45

    Article  CAS  PubMed  Google Scholar 

  6. Das S, Mohan V (2003) Disorders of lipid metabolism. In: Shah SN (ed) API text book of medicine, 75th edn. Association of physician of India, Mumbai, pp 250–258

    Google Scholar 

  7. Bhattaram VA, Ceraefe M, Kohlest C, Vest M, Deundorf H (2002) Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine 9:1–36

    Article  CAS  PubMed  Google Scholar 

  8. Bailey CJ, Day C (1989) Traditional plant medicines as treatments for diabetes. Diabetes Care 12:553–564

    Article  CAS  PubMed  Google Scholar 

  9. Mitra SK, Gopumadhavan S, Muralidhar TS, Anturlikar SD, Sujatha MB (1996) Effect of a herbomineral preparation D-400 in streptozotocin induced diabetic rats. J Ethnopharmacol 54:41–46

    Article  CAS  PubMed  Google Scholar 

  10. Annapurna A, Kanaka S, Mahalakshmi D, Murali KK (2001) Antidiabetic activity of a polyherbal preparation (tincture of punchparna) in normal and diabetic rats. Indian J Exp Biol 39:500–502

    CAS  PubMed  Google Scholar 

  11. Bhattacharya SK, Satyan KS, Chakrbarti A (1997) Effect of trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats. Indian J Exp Biol 35:297–299

    CAS  PubMed  Google Scholar 

  12. The WHO Expert Committee on Diabetes Mellitus. Technical report series 646, Geneva, and World Health Organisation 1980

  13. Banerji A, Chadha MS, Malshet VG (1969) Isolation of 5-hydroxy-3,6,7,3′,4′-pentamethoxy flavone from Vitex negundo. Phytochemistry 8:511–512

    Article  CAS  Google Scholar 

  14. Suksamaran A, Kumpun S, Kirtikara K, Yingyongnarongkul B, Suksamrarn S (2002) Iridoid with anti-inflammatory activity from Vitex peduncularis. Planta Med 68:72–73

    Article  Google Scholar 

  15. Pianaro A, Pinto JP, Ferreira TD, Ishikawa NK, Raimundo Braz-Filho RB (2007) Iridoid glucoside and antifungal phenolic compounds from Spathodea campanulata roots Semina: Ciencias Agrarias. Londrina 28:251–256

    CAS  Google Scholar 

  16. Sundaram R, Naresh R, Ranadevan R, Shanthi P, Sachdanandam P (2012) Effect of iridoid glucoside on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolic enzymes. Eur J Pharmacol 674:460–467

    Article  CAS  PubMed  Google Scholar 

  17. Sundaram R, Naresh R, Ranadevan R, Shanthi P, Sachdanandam P (2012) Antihyperglycemic effect of iridoid glucoside, isolated from the leaves of Vitex negundo in streptozotocin-induced diabetic rats with special reference to glycoprotein components. Phytomedicine 19:211–216

    Article  CAS  PubMed  Google Scholar 

  18. Ramesh B, Pugalendi KV (2006) Antioxidant role of Umbelliferone in STZ-diabetic rats. Life Sci 79:306–310

    Article  CAS  PubMed  Google Scholar 

  19. Folch J, Lees M, Solane SGH (1957) A simple method for isolation and purification of total lipids from animal tissues. J Biol Chem 26:497–509

    Google Scholar 

  20. Zilversmit DB, Davis AK (1950) Micro determination of phospholipids by TCA precipitation. J Lab Clin Med 35:155–159

    CAS  PubMed  Google Scholar 

  21. Falholt K, Falholt W, Lund B (1973) An easy colorimetric method for routine determination of free fatty acid in plasma. Clinica Chimca Acta 46:105–111

    Article  CAS  Google Scholar 

  22. Morales MA, Jobbagy AJ, Terenzi HF (1973) Mutations affecting accumulation of glycogen. Neurospora News Lett 20:24–25

    Google Scholar 

  23. Morrison WR, Smith LM (1964) Preparations of fatty acid methyl esters and dimethylac- etals from lipids with boron fluoride methanol. J Lipid Res 5:600–607

    CAS  PubMed  Google Scholar 

  24. Dombrowski L, Roy D, Mareotte B, Marette A (1996) A new procedure for the isolation of plasma membrane, T-tubules and internal membranes from skeletal muscles. Am J Physiol 270:E667–E676

    CAS  PubMed  Google Scholar 

  25. Lowry OH, Rosenbrough NJ, Farr AI, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265

    CAS  PubMed  Google Scholar 

  26. Stamler JS, Vaccaro O, Neaton D (1993) Wentworth, diabetes, other risk factors and 12 year cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 16:434–444

    Article  CAS  PubMed  Google Scholar 

  27. Kanters SDJM, Banga JD, Erkelens DW (2001) Lipid-lowering therapy in diabetes mellitus. Neth J Med 58:214–222

    Article  Google Scholar 

  28. Maghrani M, Lemhadri A, Zeggwagh NA, El Amraoui A, Haloui M, Jouad M, Eddouks M (2004) Effect of Retama raetam on lipid metabolism in normal and recent onset diabetic rats. J Ethnopharmacol 90:323–329

    Article  CAS  PubMed  Google Scholar 

  29. Rhoads GS, Gulbrandse CL, Kagan A (1976) Serum lipoproteins and coronary artery diseases in a population study of Hawaii, a Japanese man. N Engl J Med 294:293–298

    Article  CAS  PubMed  Google Scholar 

  30. Goodman LS, Gilman A (1985) The Pharmacological Basis of Therapeutics, 7th edn. MacMillan, New York, p 490

    Google Scholar 

  31. Cameron NE, Cottter MA (1997) Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes. Diabetes Res Clin Pr 45:137–146

    Article  Google Scholar 

  32. Pelikanova T, Kohout M, Valek J, Base J, Stefka Z (1991) Fatty acid composition of serum lipids and erythrocyte membranes in type 2 (non-insulin dependent) diabetic men. Metabolism 40:175–180

    Article  CAS  PubMed  Google Scholar 

  33. Folsom AR, Ma J, McGovern PG, Eckfeldt H (1996) Relation between plasma phospholipid saturation fatty acids and hyperinsulinemia. Metabolism 45:223–228

    Article  CAS  PubMed  Google Scholar 

  34. Vessby B (2000) Dietary fat and insulin actions in humans. Brit J Nutr 83:91–96

    Article  Google Scholar 

  35. Ravi P, Dai S, Tam KC (2005) Synthesis and self assembly of [6O] fullerene containing sulfobetaine polymer in aqueous solution. J Phys Chem B Condens Matter Mater. Surf Interfaces Biophys 8:22791–22798

    Google Scholar 

  36. Murugan P, Pari L (2007) Protective role of tetrahydrocurcumin on changes in the fatty acid composition in streptozotocin–nicotinamide induced type 2 diabetic rats. J Applied Biomed 5:31–38

    CAS  Google Scholar 

  37. Demaison L, Sergiel JP, Moreau D, Grynberg A (1994) Influence of the phospholipid n-6/n-3 polyunsaturated fatty acid ratio on the mitochondrial oxidative metabolism before and after myocardial ischemia. Biochimica Biophysica Acta 127:53–59

    Article  Google Scholar 

  38. Robertson RP (2004) Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 279:42351–42354

    Article  CAS  PubMed  Google Scholar 

  39. Kaneto H, Kawamori D, Matsuoka TA, Kajimoto Y, Yamasaki Y (2005) Oxidative stress and pancreatic beta-cell dysfunction. Am J Ther 12:529–533

    Article  PubMed  Google Scholar 

  40. Leung PS, Chan YC (2009) Role of oxidative stress in pancreatic inflammation. Antioxid Redox Sign 11:135–165

    Article  CAS  Google Scholar 

  41. Kaneto H, Matsuoka T, Nakatani Y, Kawamori D, Matsuhisa M, Yamasaki Y (2005) Oxidative stress and the JNK pathway in diabetes. Curr Diabetes Rev 1:65–72

    Article  CAS  PubMed  Google Scholar 

  42. Saghizadesh M, Ong JM, Garvey WT, Henry RR, Kern PA (1996) The expression of TNF-α by human muscle. Relationship to insulin resistance. J Clin Invest 97:1111–1116

    Article  Google Scholar 

  43. Devaraj S, Jialal I (2000) Antioxidants and vitamins to reduce cardiovascular disease. Curr Atheroscler Rep 2:342–351

    Article  CAS  PubMed  Google Scholar 

  44. Halse R, Pearson SL, McCormack JG, Yeaman SJ, Taylor R (2001) Effects of tumor necrosis factor-a on insulin action in cultured human muscle cells. Diabetes 50:1102–1109

    Article  CAS  PubMed  Google Scholar 

  45. Kern PA, Ranganathan S, Li C (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:745–751

    Google Scholar 

  46. Rui L, Aguirre V, Kim JK, Shulman GI, Lee A, Corbould A, Dunaif A, White MF (2001) Insulin/IGF-1 and TNF- stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest 107:181–189

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Singh U, Devraj S, Jialal I (2005) Vitamin E, oxidative stress and inflammation. Annu Rev Nutr 25:151–174

    Article  CAS  PubMed  Google Scholar 

  48. Andreozzi F, Laratta E, Cardellini M (2006) Plasma interleukin-6 levels are independently associated with insulin secretion in a cohort of Italian-Caucasian nondiabetic subjects. Diabetes 55:2021–2024

    Article  CAS  PubMed  Google Scholar 

  49. Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11:372–377

    Article  CAS  PubMed  Google Scholar 

  50. Yudkin JS, Stehouwer CD, Emeis JJ (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19:972–978

    Article  CAS  PubMed  Google Scholar 

  51. Rosenstock M, Greenberg AS, Rudich A (2001) Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes. Diabetologia 44:55–62

    Article  CAS  PubMed  Google Scholar 

  52. Cavallo MG, Pozzilli P, Bird C, Wadhwa M, Meager A, Visalli N, Gearing AJ, Andreani D, Thorpe R (1991) Cytokines in sera from insulin dependent diabetic patients at diagnosis. Clin Exp Immunol 86:256–259

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Hussain MF, Peakman M, Gallati H, Lo SS, Hawa M, Viberti GC, Watkins PJ, Leslie RD, Vergani D (1996) Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia 39:60–69

    CAS  PubMed  Google Scholar 

  54. Rader DJ (2000) Inflammatory markers of coronary risk. N Engl J Med 343:1179–1182

    Article  CAS  PubMed  Google Scholar 

  55. Jain SK, Kannan K, Lim G, Matthew-Greer J, McVie R, Bocchini JA (2003) Elevated blood interleukin-6 levels in hyperketonemic type 1 diabetic patients and secretion by acetoacetate-treated cultured U937 monocytes. Diabetes Care 26:2139–2143

    Article  CAS  PubMed  Google Scholar 

  56. Peraldi P, Spiegelman B (1998) TNF-alpha and insulin resistance: summary and future prospects. Mol Cell Biochem 182:169–175

    Article  CAS  PubMed  Google Scholar 

  57. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and oxidative stress. J Clin Invest 115:1111–1119

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Jialal I, Devraj S, Venugopal SK (2004) C-reactive protein: risk marker or mediator in atherothrombosis. Hypertension 44:6–11

    Article  CAS  PubMed  Google Scholar 

  59. Kainulainen H, Breiner M, Schurmann A, Marttinen A, Virjo A, Joost HG (1994) In vivo glucose uptake and glucose transporter proteins GLUT1 and GLUT4 in heart and various types of skeletal muscle from streptozotocin-diabetic rats. Biochim Biophys Acta 1225:275–282

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Palanivelu Shanthi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sundaram, R., Shanthi, P. & Sachdanandam, P. Effect of iridoid glucoside on plasma lipid profile, tissue fatty acid changes, inflammatory cytokines, and GLUT4 expression in skeletal muscle of streptozotocin-induced diabetic rats. Mol Cell Biochem 380, 43–55 (2013). https://doi.org/10.1007/s11010-013-1656-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1656-0

Keywords

Navigation