Abstract
BackgroundHydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. However, underlying mechanism of HSYA is not fully elucidated. The present study investigated the protective effects of HSYA in rat spinal cord compression injury model and related mechanisms involved.MethodsSprague–Dawley rats were divided as Sham, Control, and HSYA groups (n = 30 per group). Spinal cord injury (SCI) model was induced by application of vascular clips (force of 50 g, 1 min) to the dura at T9–T10 level of vertebra. Injured animals were administered with either HSYA (8 mg/kg at 1 and 6 h after injury, then 14 mg/kg, for a total of 7 days at 24-h time intervals) or equal volume of saline by intraperitoneal injection.ResultsFrom this experiment, we discovered that SCI in rats resulted in severe trauma, which is characterized by tissue damage, lipid peroxidation, neutrophil infiltration, inflammation mediator release, and neuronal apoptosis. However, HSYA treatment significantly reduced the following: (1) degree of tissue injury (histological score) and edema; (2) neutrophil infiltration (myeloperoxidase activity); (3) oxidative stress (superoxide dismutase, malondialdehyde, and nitric oxide); (4) pro-inflammatory cytokine expression (tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2); (5) nuclear factor-κB activation; (6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining and cysteine-aspartic protease-3 activity). Moreover, in a separate set of experiments, we clearly demonstrated that HSYA treatment significantly ameliorated recovery of limb function (as evaluated by Basso, Beattie, and Bresnahan behavioral recovery scores).ConclusionsTreatment with HSYA restrains development of oxidative stress, inflammation response, and apoptotic events associated with SCI of rats, demonstrating that HSYA is a potential neuroprotectant for human SCI therapy.
Highlights
Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo
Results suggest that Spinal cord injury (SCI) can induce production of pro-inflammatory cytokines in spinal cord, and this effect can be significantly alleviated by HSYA treatment
HSYA inhibits nuclear transcription factor-κB (NF-κB) activation To investigate whether changes in inflammatory cytokines in spinal cord are associated with attenuation of NF-κB activation, NF-κB/DNA binding was analyzed by Electrophoretic mobility shift assay (EMSA)
Summary
Hydroxysafflor yellow A (HSYA) is a major active component of yellow pigment extracted from safflowers; this compound possesses potent neuroprotective effects both in vitro and in vivo. Traumatic SCI is characterized by primary injury and secondary neuronal death involving a large number of cellular, molecular, and biochemical cascades, which when controlled ineffectively, result in more extensive and sustained damages [2,3,4]. These pathological events can increase blood–spinal cord barrier (BSCB) permeability, tissue edema, peroxidation of lipid membranes, inflammatory cytokine release, and neural cell apoptosis [4, 5]. New pharmacological therapies must be developed; such treatments should reduce evolution of secondary injury of SCI
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