acteoside and Spinal-Cord-Injuries

Chronic spinal cord injury (SCI) is difficult to cure, even by several approaches effective at the acute or subacute phase. We focused on skeletal muscle atrophy as a detrimental factor in chronic SCI and explored drugs that protect against muscle atrophy and activate secretion of axonal growth factors from skeletal muscle. We found that acteoside induced the secretion of axonal growth factors from skeletal muscle cells and proliferation of these cells. Intramuscular injection of acteoside in mice with chronic SCI recovered skeletal muscle weight reduction and motor function impairment. We also identified pyruvate kinase isoform M2 (PKM2) as a secreted factor from skeletal muscle cells, stimulated by acteoside. Extracellular PKM2 enhanced proliferation of skeletal muscle cells and axonal growth in cultured neurons. Further, we showed that PKM2 might cross the blood-brain barrier. These results indicate that effects of acteoside on chronic SCI might be mediated by PKM2 secretion from skeletal muscles. This study proposes that the candidate drug acteoside and a new myokine, PKM2, could be used for the treatment of chronic SCI.

Topics: Animals; Animals, Newborn; Antioxidants; Cells, Cultured; Dose-Response Relationship, Drug; Female; Glucosides; Mice; Motor Activity; Muscle, Skeletal; Muscular Atrophy; Phenols; Pyruvate Kinase; Spinal Cord Injuries; Thoracic Vertebrae

In this study we evaluated the effect of glycosylated phenylpropanoid verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa vulgaris (Oleaceae) in experimental animal model of spinal cord injury (SCI). SCI was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis. At 1 and 6 h after injury, the mice were treated with VB extract, administered at the dose of 2 mg/kg with intraperitoneal administration. Immunohistochemical examination demonstrated a marked increase on expression for nitrotyrosine, inducible nitric oxide synthase, poly(ADP-ribose), and apoptosis events (increase of Bax and Bcl-2 expression) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the cytokines expression (TNF-α and IL-1β), neutrophil infiltration (myeloperoxidase), and activation of NF-κB. In contrast, all of these parameters of inflammation were attenuated by treatment with VB. In a separate set of experiment, we have clearly demonstrated that VB treatment significantly ameliorated the recovery of function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with VB extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cell Culture Techniques; Chromatography, High Pressure Liquid; Disease Models, Animal; Glucosides; Immunohistochemistry; In Situ Nick-End Labeling; Injections, Intraperitoneal; Interleukin-1beta; Male; Mice; Mice, Inbred Strains; Motor Activity; Nitric Oxide Synthase Type II; Phenols; Plant Extracts; Poly Adenosine Diphosphate Ribose; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Spinal Cord; Spinal Cord Injuries; Syringa; Tumor Necrosis Factor-alpha; Tyrosine