Curcumin modulates TLR4/NF-κB inflammatory signaling pathway following traumatic spinal cord injury in rats

Abstract

Background: Curcumin, a polyphenolic compound extracted from the plant turmeric, has protective effects on spinal cord injury (SCI) through attenuation of inflammatory response. This study was designed to detect whether curcumin modulates toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in the injured rat spinal cord following SCI. Methods: Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. There were three groups: (a) sham group; (b) SCI group; and (g) SCI + curcumin group. We measured TLR4 gene and protein expression by real-time polymerase chain reaction and western blot analysis; NF-κB activity by electrophoretic mobility shift assay, inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels by enzyme-linked immunosorbent assay, hindlimb locomotion function by Basso, Beattie, and Bresnahan rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. Results:The results showed that SCI induced the up-regulation of TLR4, NF-κB, and inflammatory cytokines in the injured rat spinal cord. Treatment with curcumin following SCI markedly down-regulated the levels of these agents related to the TLR4/NF-κB inflammatory signaling pathway. Administration of curcumin also significantly ameliorated SCI induced hind limb locomotion deficits, spinal cord edema, and apoptosis. Conclusions: Post-SCI curcumin administration attenuates the TLR4/NF-κB inflammatory signaling pathway in the injured spinal cord, and this may be a mechanism whereby curcumin improves the outcome following SCI.

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar

“…Jin et al [22,30] showed that cur (100 mg/kg) given to animals 7 d after spinal cord hemisection reduced the cytokines TNF-a, IL-1b, and IL-6 expression, suppressed NF-kb signaling pathway activation, and decreased the severity of locomotion deficit. Similarly, cur treatment (50 mg/kg) once daily for 7 d after injury exerted an anti-inflammatory property through NF-kb signaling pathway, decreased glial scar intracellular composition GFAP expression, and improved functional recovery [31].…”

Protective effects of the suppressed NF‐κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury

“…Toll‐like receptors (TLRs) are a kind of trans‐membrane proteins and signal transduction molecules . TLR4 is a pattern recognition receptor, typically known to play a major role in generating an inflammatory response by way of distinguishing exogenous pathogen‐associated and endogenous damage‐associated molecular patterns .…”

“…10,11 Toll-like receptors (TLRs) are a kind of trans-membrane proteins and signal transduction molecules. 12 TLR4 is a pattern recognition receptor, typically known to play a major role in generating an inflammatory response by way of distinguishing exogenous pathogenassociated and endogenous damage-associated molecular patterns. 13 The effects of TLR4 and NF-κB signaling pathway in several types of tissues have been highlighted in previous studies, including liver and pancreas tissues.…”

Curcumin decreases astrocytic reaction after gliotoxic injury in the rat brainstem

“…Recently, Cur has been shown to exhibit proven therapeutic benefits (including antioxidant, anti-inflammatory, anti-cancer and anti-fibrotic effects) in many pathological conditions, such as Alzheimer' s disease, Parkinson' s disease, multiple sclerosis, epilepsy, cerebral injury, cancer, allergy, asthma, bronchitis, colitis, rheumatoid arthritis, renal ischemia, psoriasis, scleroderma, diabetes, obesity, depression, fatigue and acquired immunodeficiency disease 6,7,8 . Specifically regarding the CNS, Cur was capable of providing neuroprotection after spinal cord injury, inhibiting apoptosis and neuron loss and attenuating oxidative stress in astrocytes and reactive astrogliosis 9,10,11,12,13 , suggesting that Cur might beneficially affect astrocyte population in the CNS inflammatory environment by regulating both NF-κβ and SOX9 signaling pathways 14,15 . In this context, the aim of this study was to evaluate whether Cur had the capacity to affect astrocyte response during the process of demyelination and remyelination following gliotoxic injury induced by ethidium bromide (EB).…”