Table 1.

The role of NF-κB in DN.

Mechanism	Highlights	Ref
HMGB1/TKR4/NF-κB	Memantine alleviated pain indicators in diabetic mice and suppressed excessive NMDAR1 activation, glutamate, and pro-inflammatory cytokine release in the spinal cord. Furthermore, memantine combats the HMGB1/TLR4/NF-kB axis and modulates overactive glutamate spinal transmission	[49]
NF-κB	NF-κB expression in diabetic sciatic endothelial cells and Schwann cells increased significantly, with a 2-fold increase in NF-κB and ICAM-1 expression density in diabetic nerve microvessels. Moreover, diabetic nerves experience an increased inflammatory response due to IR injury, possibly due to NF-κB activation	[48]
TNF-α/NF-κB	Increased Nav1.7 in DRG neurons of rats with DN was linked to increased TNF-α, which was inhibited by thalidomide and pyrrolidine dithiocarbamate. The NF-κB is involved in this process	[53]
MAPK/NF-κB	GLP-1R agonists prevent nerve dysfunction in the sciatic nerves of diabetic rats via p38 MAPK/NF-κB is independent of glycemic control	[77]
NF-κB	The study reveals that ZJME, ARBWF, and ZJWF, when combined with insulin, can reduce thermal, mechanical hyperalgesia, cold allodynia in diabetic neuropathic rats, reducing oxidative stress, NF-κB, and iNOS-mediated inflammatory cascades	[78]
NF-κB	HG treatment increased DRG neuron apoptosis by increasing ROS levels and activating the NF-κB. Quercetin, when combined with HG, decreased caspase-3 activation and apoptosis, directly scavenging ROS, increasing Nrf-2 and HO-1 expression, and inhibiting NF-κB signaling, suppressing inflammatory cytokines	[79]
NF-κB	The study confirms the NF-κB inhibitory and anti-inflammatory activity of resveratrol, which may contribute to neuroprotection in diabetic neuropathy, by decreasing p65 and IκB-α expression, ameliorating elevated TNF-α, IL-6, and COX-2 levels, and reducing nerve MDA levels	[80]
TLR4/NF-κB	Quercetin reduced inflammatory factors in diabetic pancreatic cancer (DPN) rats by downregulating the TLR4/MyD88/NF-κB. Despite not decreasing blood glucose levels or reversing weight loss, it demonstrated anti-inflammatory and neuroprotective effects, making it beneficial for DPN treatment	[81]
NF-κB	Curcumin can enhance spinal cord changes, inhibit Iba1, GFAP, caspase-3, and NF-kB expression, increase NeuN expression, and restore Nrf2/HO-1 signaling, thus suppressing diabetic spinal cord central neuropathy, glial activation, and neuronal apoptosis	[82]
NF-κB	DRG neurons' apoptosis was enhanced in diabetic conditions, which was lessened by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1, scavenging ROS, and prevention of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers	[83]
NF-κB	Melatonin reduces NF-κB, IκB-α, and phosphorylated IκB-α expression, proinflammatory cytokines, and DNA fragmentation in animal sciatic nerves. It modulates Nrf2, increasing heme oxygenase-1 expression and strengthening antioxidant defense. Melatonin has neuroprotective effect in diabetic neuropathy	[76]