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 May 1;658(1):41-8. doi: 10.1016/j.ejphar.2011.02.010. Epub 2011 Feb 22.

Abstract

Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. The present study was undertaken to investigate the therapeutic potential of curcumin, a dietary spice with antioxidant activity, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Diabetes was induced in mice by multiple low doses of streptozotocin. After the onset of diabetes, mice were treated with curcumin (10 mM; 100 μl/mouse, i.p., for 28 days) or received a single bone marrow transplantation (10(6) un-fractionated bone marrow cells), or both. Parameters of diabetes, integrity of pancreatic islets, pancreatic oxidative stress markers, and serum pro-inflammatory cytokines, were evaluated. Treatment with either curcumin or bone marrow transplantation significantly reversed streptozotocin-induced hyperglycemia/glucose intolerance, hypoinsulinemia, and damage of pancreatic islets. Interestingly, combination of curcumin and bone marrow transplantation elicited the most profound alleviation of such streptozotocin-evoked anomalies; including islet regeneration/insulin secretion. On the other hand, curcumin, either alone or combined with bone marrow transplantation, blunted the pancreatic lipid-peroxidation, up-regulated activities of the antioxidant enzymes, and suppressed serum levels of TNF-α and IL-1β. Curcumin and single bone marrow transplantation proved their therapeutic potential in reversing diabetes when used in combination. Curcumin, via its antioxidant and anti-inflammatory effects, evidently enhanced the ability of bone marrow transplantation to regenerate functional pancreatic islets. Hence, the use of natural antioxidants combined with other therapeutic regimens to induce pancreatic regeneration is a promising strategy in the management of diabetes.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Bone Marrow Transplantation*
  • Curcumin / pharmacology*
  • Cytokines / blood*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / therapy*
  • Glucose Tolerance Test
  • Inflammation / blood
  • Inflammation / metabolism
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Interleukin-1beta / blood
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiopathology
  • Lipid Peroxidation / drug effects
  • Mice
  • Oxidative Stress / drug effects*
  • Regeneration / drug effects*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antioxidants
  • Blood Glucose
  • Cytokines
  • Insulin
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Curcumin