Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation

Rahimifard, Mahban; Maqbool, Faheem; Moeini-Nodeh, Shermineh; Niaz, Kamal; Abdollahi, Mohammad; Braidy, Nady; Nabavi, Seyed Mohammad

doi:10.1016/j.arr.2017.02.004

Cited by 362 publications

(222 citation statements)

References 92 publications

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“…It is known to physically bind to 33 different proteins, including thioredoxin reductase, COX2, protein kinase C (PKC), 5-lipoxygenase (5-LOX) and tubulin (Zhou et al ., 2011). Also, it can modulate nuclear factor-κB (Rahimifard et al ., 2017), growth factors, cytokines, enzymes and genes regulating cell proliferation and apoptosis, as well as microglia/macrophage or T cell-mediated immune response (Tu et al ., 2012). Although similar analgesic effects of curcumin were observed in various neuropathic animal models, the underlying mechanism varied from one study to another.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its anti-inflammatory effect, curcumin has demonstrated an analgesic effect in several animal models of neuropathic pain, such as pain in diabetes (Meng et al ., 2015) and chronic constrictive injury of spinal cord (Jeon et al ., 2013; Noorafshan et al ., 2011a). Curcumin has been reported to act on multiple cellular targets and signalling pathways suppressing production of mediators of inflammation and neuronal apoptosis, including toll-like receptors and nuclear factor-κB (Rahimifard et al ., 2017), growth factors, inflammatory cytokines and protein kinases (Zhou et al, 2011). In the search for new therapeutics to combat lumbar radiculopathy, curcumin arises as an outstanding agent, given its excellent anti-inflammatory, anti-oxidative and analgesic potentials.…”

Section: Introductionmentioning

confidence: 99%

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

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

View full text Add to dashboard Cite

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“…Moreover, curcumin increased levels of IL-10 and glutathione. Curcumin also decreased levels of toll-like receptor (TLR)-4, as well as of NF-κB, interferon regulatory factor 3, MyD88, and TIR-domain-containing adapter-inducing interferon-β otherwise enhanced by MPP+ (100). Similarly, epi and resveratrol have been found to exert neuroprotective activity modulating TLR-4/NF-κB/signal transducer and activator of transcription (STAT) signaling pathways (100).…”

Section: Cocoa and Dark Chocolate Effects On The Central Nervous Systmentioning

confidence: 99%

Cocoa and Dark Chocolate Polyphenols: From Biology to Clinical Applications

2017

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It is well known that cocoa and dark chocolate possess polyphenols as major constituents whose dietary consumption has been associated to beneficial effects. In fact, cocoa and dark chocolate polyphenols exert antioxidant and anti-inflammatory activities switching on some important signaling pathways such as toll-like receptor 4/nuclear factor κB/signal transducer and activator of transcription. In particular, cocoa polyphenols induce release of nitric oxide (NO) through activation of endothelial NO synthase which, in turn, accounts for vasodilation and cardioprotective effects. In the light of the above described properties, a number of clinical trials based on the consumption of cocoa and dark chocolate have been conducted in healthy subjects as well as in different categories of patients, such as those affected by cardiovascular, neurological, intestinal, and metabolic pathologies. Even if data are not always concordant, modifications of biomarkers of disease are frequently associated to improvement of clinical manifestations. Quite interestingly, following cocoa and dark chocolate ingestion, cocoa polyphenols also modulate intestinal microbiota, thus leading to the growth of bacteria that trigger a tolerogenic anti-inflammatory pathway in the host. Finally, many evidences encourage the consumption of cocoa and dark chocolate by aged people for the recovery of the neurovascular unit.

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“…Its main effects on neurodegeneration diseases include anti-inflammation through the NF-κB pathway, anti-oxidant effects through the Nrf2 pathway, and disaggregation of polymers [44-47]. …”

Section: Discussionmentioning

confidence: 99%

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

Wang

Yin

Gao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

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Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation

Cited by 362 publications

References 92 publications

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

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

Cocoa and Dark Chocolate Polyphenols: From Biology to Clinical Applications

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

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