hypericum and Spinal-Cord-Injuries

Oxidative stress and cytosolic Ca(2+) overload have important roles on apoptosis in dorsal root ganglion (DRG) neurons after spinal cord injury (SCI). Hypericum perforatum (HP) has an antioxidant property in the DRGs due to its ability to modulate NADPH oxidase and protein kinase C pathways. We aimed to investigate the protective property of HP on oxidative stress, apoptosis, and Ca(2+) entry through transient receptor potential melastatin 2 (TRPM2) and transient receptor potential vanilloid 1 (TRPV1) channels in SCI-induced DRG neurons of rats. Rats were divided into four groups as control, HP, SCI, and SCI + HP. The HP groups received 30 mg/kg HP for three concessive days after SCI induction. The SCI-induced TRPM2 and TRPV1 currents and cytosolic free Ca(2+) concentration were reduced by HP. The SCI-induced decrease in glutathione peroxidase and cell viability values were ameliorated by HP treatment, and the SCI-induced increase in apoptosis, caspase 3, caspase 9, cytosolic reactive oxygen species (ROS) production, and mitochondrial membrane depolarization values in DRG of SCI group were overcome by HP treatment. In conclusion, we observed a protective role of HP on SCI-induced oxidative stress, apoptosis, and Ca(2+) entry through TRPM2 and TRPV1 in the DRG neurons. Our findings may be relevant to the etiology and treatment of SCI by HP. Graphical Abstract Possible molecular pathways of involvement of Hypericum perforatum (HP) on apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in DRG neurons of SCI-induced rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress through activation of ADP-ribose pyrophosphate although it was inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA) and 2-aminoethyl diphenylborinate (2APB). The TRPV1 channel is activated by oxidative stress and capsaicin and it is blocked by capsazepine. Injury in the DRG can result in augmented ROS release, leading to Ca(2+) uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca(2+), provided intracellular Ca(2+) rises, thereby leading to depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. HP via regulation of NADPH oxidase and PKC inhibits TRPM2 and TRPV1 channels. The molecular pathway may be a cause of SCI-induced pain and neuronal death, and the subject should be urgently investigated.

Topics: Animals; Apoptosis; Calcium; Capsaicin; Caspases; Cell Survival; Ganglia, Spinal; Glutathione; Glutathione Peroxidase; Hydrogen Peroxide; Hypericum; Ion Channel Gating; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Reactive Oxygen Species; Spinal Cord Injuries; TRPM Cation Channels; TRPV Cation Channels

Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants, and/or a depletion of antioxidants. A considerable body of recent evidence suggests that oxidative stress and exaggerated production of reactive oxygen species play a major role in several aspects of inflammation. Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely, flavonoids and phenolic acids. Because polyphenolic compounds have high antioxidant potential, in this study, we evaluated the effect of H. perforatum (given at 30 mg . kg (-1)) in an experimental animal model of spinal cord injury, which was induced by the application of vascular clips to the dura via a four-level T5 through T8 laminectomy. The degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine, (c) poly(adenosine diphosphate-ribose), (d) neutrophils infiltration, and (e) the activation of signal transducer and activator transcription 3 was markedly reduced in spinal cord tissue obtained from H. perforatum extract-treated mice. We have also demonstrated that H. perforatum extract significantly ameliorated the recovery of limb function.

Topics: Animals; Hypericum; Inflammation; Male; Mice; Neutrophil Infiltration; Oxidative Stress; Phytotherapy; Plant Extracts; Poly Adenosine Diphosphate Ribose; Recovery of Function; Signal Transduction; Spinal Cord Injuries; Tyrosine