Table 2.

The role of NF-κB in DC.

Molecular pathways	Remark	Ref
NF-κB	Sophocarpine protects myocardial cells from hyperglycemia-induced injury by improving mitochondrial function, suppressing inflammation, and inhibiting cardiac apoptosis. It also slows the development of diabetic cardiomyopathy	[139]
NF-κB Wnt	The study found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways can regulate glucose and lipid metabolism, leading to decreased NF-κB activity and downregulation of proinflammatory cytokines	[140]
PI3K/Akt/NF-κB	ECL treatment significantly improved pathological changes in mice's heart tissues, alleviating injury and fibrosis. It increased Bcl-2 levels, decreased Bax, cle-caspase-3, and cle-caspase-9 expression, and inhibited NF-κB nuclear translocation, increasing PI3K and p-Akt expressions	[141]
NF-κB NADPH	Polydatin inhibited hyperglycemia-induced reactive oxygen species, NADPH oxidase activity, and inflammatory cytokine production, while also preventing increased expression of NOX4, NOX2, and NF-κB in H9c2 cells and diabetic hearts	[142]
NF-κB	LBP treatment in diabetic rats improves cardiac hypertrophy, inhibits calpain-1 expression, and inhibits NF-κB activation, while reducing reactive oxygen species production, increasing p65 protein expression, and downregulating nitric oxide synthase	[143]
CXCR4/NF-κB	The Akitains2 heart, a type 1 diabetic model, is protected against systolic failure due to increased NCX1 expression, as CXCR4 activation upregulates NCX1 expression through a NF-κB-dependent in the cardiac myocyte	[144]
NF-κB ROS	L6H9 significantly reduced cardiac cytokine and ROS levels, improved histological abnormalities and fibrosis, and attenuated diabetes-induced NF-κB activation and Nrf2 decrease	[145]
ROS NF-κB	Klotho pretreatment effectively inhibited glucose-induced inflammation, ROS generation, apoptosis, mitochondrial dysfunction, fibrosis, and hypertrophy in H9c2 cells and neonatal cardiomyocytes, and suppressed cardiac inflammatory cytokines in STZ-induced type 1 diabetic mice. Klotho may enhance Nrf2 expression and inactivate NF-κB activation	[146]
TLR4/NF-κB	High-glucose culture of H9C2 cells leads to decreased cell activity, increased apoptosis, and oxidative stress. The HG + si-ILK group increases activity, decreases apoptosis, and inhibits TLR4/MyD88/NF-κB signaling, improving oxidative stress and inflammation	[147]
PKC/NF-κB	Metoprolol and bisoprolol could prevent hypertrophy of cardiomyocytes cultured in high glucose by the inhibition of the total and phospho-PKC-α, which could further influence the PKC-α/NF-κB/c-fos	[148]
PKC/NF-κB/c-fos	High glucose significantly increased the pulsatile frequency and cellular volumes of cultured cardiomyocytes via PKC/NF-κB/c-fos, which might lead to diabetic cardiomyopathy	[149]
CD36/NF-κB	HG-induced upregulation of CD36 promotes inflammatory stress via NF-κB in H9c2 cells, mediated by metabolism reprogramming, lipid accumulation and enhanced ROS generation	[150]
NF-κB MAPK	Liquiritin reduces inflammatory cytokine release and NF-κB phosphorylation through IKKα/IκBα suppression. It inactivates Mitogen-activated protein kinases (MAPKs) up-regulated for fructose stimulation, protecting against high fructose-induced myocardial fibrosis	[151]
Siti1/NLRP3/NF-κB	BE improved glocose tolerance, reduced lipid accumulation, and inflammatory cytokine content in diabetic mice, regulating the Siti1/NLRP3/NF-κB. Siti1 inhibitor (EX-57) counteracted these changes and protected against diabetic cardiomyopathy	[152]
NF-κB	pre-existing type 2 diabetes phenotype worsens the organ dysfunction/injury associated with CLP-sepsis in mice. Moreover, prevention of NF-κB reduces the organ dysfunction/injury associated with sepsis in mice with pre-existing T2DM	[153]
NF-κB	Diabetes-induced heart damage and increased nitrative modifications of key energy metabolism enzymes were observed in diabetic mice overexpressing catalase. Bay11-7082, an inhibitor of the NF-κB, protected mice from cardiac damage and increased nitrative modifications	[154]
NF-κB	Hyperglycemia (HG) reduced cell viability and apoptosis in H9c2 cells, increased ROS production, IL-6, and TNF-α levels, and overexpressed NF-[kappa]B. However, pretreatment with 6-shogaol improved cell viability and reduced apoptosis	[155]
TLR4/NF-κB	Diabetes nephropathy markers, FN and TGF-β1, are reduced in HG-treated GMCs by TGR5, which is mediated by NF-κB. The inhibition of RhoA/ROCK by PKA is closely related to these roles	[156]