Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Abstract

Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (µCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy.

Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases

“…In an LPS-induced PD model, curcumin inhibits astrocyte activation and NADPH oxidase complex activation by downregulating NF- κ B activity, intrinsic apoptotic pathway (Bax, Bcl-2, caspase 3, and caspase 9), proinflammatory cytokines (TNF- α , IL-1 β , and IL-1 α ), and inducible NOS [ 79 ]. In primary neuron culture, curcumin effectively inhibits TNF- α -induced neuroinflammation (IL-6 and Cox-2), protects neurons from excessive ROS production and cellular apoptosis, and promotes expression of antioxidative enzymes HO-1, catalase, and SOD-2 [ 80 ]. Recently, conjugated curcumins such as nanocurcumin or curcumin-like analogs are developed to increase their bioavailability and potential neuroprotective efficacy in PD.…”

Effect of curcumine on the formation of epidural fibrosis in an experimental laminectomy model in rats

“…It is known that macrophages show these effects by increasing the function of factors such as TGF-β, TGF-α, basic FGF, PDGF and vascular endothelial growth factor that increase proliferation and cell synthesis. Several studies suggest that curcumin decreases the amount of these factors (23). On the other hand, IL-6 and TGF-β1 has been shown to be effective on EF (3).…”

“…Prior studies have also suggested that this mediator induces the amount of IL-6, prostaglandin E2 (PGE2), cyclooxygenase (COX-2) that have an important role in inflammation. Curcumin suppresses TNF-α-induced neuroinflammation IL-6, PGE2, COX-2 at a significant level (23). Moreover; curcumin has been shown to decrease post traumatic inflammation due to its anti-inflammatory properties in experimental spinal cord trauma studies (2).…”

Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy

“…Under a hypoxic state it can increase the permeability of BBB by upregulating the expression of heme oxygenase-1 (HO-1) in microvascular endothelial cells 164 . In addition, Xiao et al 165 showed that curcumin can protect neurons from TNF- α -triggered excessive ROS production and cellular apoptosis. Correspondingly, it promoted mRNA expression of anti-oxidative enzymes like HO-1, catalase and superoxide dismutase-2.…”