Pharmacological protection of mitochondrial function mitigates acute limb ischemia/reperfusion injury

Bioorg Med Chem Lett. 2016 Aug 15;26(16):4042-51. doi: 10.1016/j.bmcl.2016.06.079. Epub 2016 Jun 28.

Abstract

We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function.

Keywords: Anti-inflammatory activity; Curcumin analogues; Free radical scavenging activity; Ischemia/reperfusion injury; Thrombolytic activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use
  • Cytochromes c / metabolism
  • Disease Models, Animal
  • Edema / prevention & control
  • Enzyme-Linked Immunosorbent Assay
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Free Radical Scavengers / therapeutic use
  • Human Umbilical Vein Endothelial Cells
  • Interleukin-6 / blood
  • Mice
  • Microscopy, Fluorescence
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Quantum Theory
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / pathology
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anti-Inflammatory Agents
  • Free Radical Scavengers
  • Interleukin-6
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Cytochromes c
  • Curcumin