Table 4.

A summary of the drugs regulating NF-κB in diabetes therapy.

Drug	Diabetic complication	Remark	Ref
Wogonin	Diabetic nephropathy	Wogonin inhibited phosphoinositide 3-kinase (PI3K), a key target of pro-inflammatory cytokines, thereby reducing autophagic dysfunction and thereby reducing its protective effect.Wogonin regulated autophagy and inflammation via targeting PI3K, the important connection point of PI3K/Akt/NF-κB signaling pathway	[204]
Huangkui capsule	Diabetic nephropathy	In contrast to RAP, HKC has the ability to ameliorate renal tubular EMT in rats that have been modelled with DN. This is most likely accomplished by reducing the activation of NLRP3 inflammasomes and TLR4/NF-κB signaling in the kidneys	[196]
20(R)-Rg3	Diabetic nephropathy	HFD/STZ mice had elevated FBG levels, leading to DN, increased cholesterol, and malondialdehyde overproduction. Treatment with 20(R)-Rg3 improved insulin, blood lipids, oxidative stress, and renal function. 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation	[205]
Dapagliflozin	Diabetic nephropathy	Dapagliflozin significantly reduced oxygen consumption, HIF-1α, HE4, NF-κB expression, and apoptotic cells in diabetic rats, increasing renal function and immunohistochemistry, but causing higher creatinine and urea nitrogen levels. Dapagliflozin ameliorate CI-AKI through suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo	[206]
Sanziguben polysaccharides	Diabetic nephropathy	Sanziguben polysaccharide decreased urine albumin levels in diabetic mice, decreased insulin resistance, creatinine, and blood urea nitrogen levels, mitigated renal damage, and regulated gut microbiota. It inhibited TLR4, phospho–NF–κB p65, NLRP3 proteins, and IL-18 and IL-1β expression levels. Sanziguben polysaccharide improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN	[223]
Phillyrin	Diabetic cardiomyopathy	Phillyrin administration significantly improved cardiac function, reduced hypertrophic markers, and reduced inflammation in left ventricular tissue. It also inhibited phosphorylation of proinflammatory genes and attenuated cardiomyocyte hypertrophy in NE-treated H9c2 cells, reducing ROS production and phosphorylation in heart tissues. Phillyrin alleviates NE-induced cardiac hypertrophy and inflammatory response by suppressing p38 MAPK/ERK1/2 and AKT/NF-κB signaling pathways	[207]
Kirenol	Diabetic nephropathy	Kirenol treatment significantly reduced Smad2/3 and NF-κB phosphorylation, FN and Col IV accumulation, IκBα expression, IL-6 and TNF-α expression, and alleviated glomerular basement membrane thickness and foot process fusion compared to the DM group. Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway	[208]
Luteolin	Diabetic cardiomyopathy	Luteolin reduces HG-induced inflammatory phenotype and oxidative stress in H9C2 cardiomyocytes by inhibiting NF-κB and activating Nrf2 signaling, reducing matrix protein expression and cellular hypertrophy. It also protects heart tissues in diabetic mice	[104]
Curcumin analog JM-2	Diabetic cardiomyopathy	JM-2, a new curcumin analog, prevents cardiac dysfunction, reduces inflammation, and attenuates diabetic ketoacidosis by inhibiting NF-κB activation in the heart. It also prevents proinflammatory factors and macrophage infiltration in T1DM and T2DM mice, and suppresses high glucose-induced myocardial hypertrophy and fibrosis	[122]
Tilianin and syringin	Diabetic cardiomyopathy	The combination of syringin and tilianin reduced oxidative stress in rats' hearts, suppressed diabetes-induced stress, and improved cardiac function. It also inhibited mitochondrial membrane depolarization, ROS production, caspase-3 and Bax/Bcl2 expression, and up-regulated TLR4, MyD88, and NF-κB in diabetic rats. However, 3-TYP's inhibition reversed the benefits due to the crosstalk between TLR4/NF-κB/NLRP3 and PGC1α/SIRT3/mitochondrial pathways	[130]
LCZ696	Diabetic cardiomyopathy	LCZ696 and valsartan improved DCM progression by inhibiting AGEs formation, pro-apoptotic markers, NF-κB, and protein levels. They attenuated DCM by inhibiting myocardial inflammation, ER stress, and apoptosis through AGEs/NF-κB and PERK/CHOP signaling cascades	[107]
Isosteviol	Diabetic cardiomyopathy	STVNa treatment effectively inhibited cardiac hypertrophy, fibrosis, and inflammation, maintaining a heart-to-body weight ratio and antioxidant capacities. It also inhibited diabetes-induced ERK and NF-κB signal pathways without altering blood glucose, plasma AGE, and insulin levels, suggesting STVNa could be a potent therapy for DCM	[108]
Atorvastatin	Diabetic cardiomyopathy	HG-induced cardiomyocyte apoptosis can be reduced by GSK-3β phosphorylation, PP2A catalytic subunit C, and IKK/IкBα, leading to NF-кB nuclear translocation and apoptosis. Treatment with okadaic acid or silencing PP2Ac increased these effects	[126]
Sophocarpine	Diabetic cardiomyopathy	Sophocarpine protects myocardial cells from hyperglycemia-induced injury by improving mitochondrial function, suppressing inflammation, and inhibiting cardiac apoptosis. It inhibits NF-κB signaling in high-glucose-stimulated inflammatory responses and slows the development of diabetic coronary syndrome in STZ-induced diabetic mice	[139]
Andrographolide	Diabetic cardiomyopathy	Andro treatment effectively inhibits hyperglycemia-induced reactive oxygen species generation by suppressing NOX activation and increasing Nrf2 expression, thereby promoting cardioprotective effects through modulation of NOX/Nrf2-mediated oxidative stress and NF-κB-mediated inflammation	[128]
Allisartan isoproxil	Diabetic cardiomyopathy	The study found that allisartan isoproxil reduces SIRT1 and Nrf2 expression in diabetic rats' hearts, decreases antioxidant defenses, NF-κB p65 expression, TNF-α and IL-1β expression, and decreases cardiac Bax and cleaved caspase-3 levels, suggesting it alleviates diabetic heart disease	[115]
Polyherbal Formulation	Diabetic cardiomyopathy	Polyherbal formulation effectively reduced inflammation and oxidative stress by upregulating Nrf-2, HO-1, superoxide dismutase, and catalase, while downregulating TNF-α and NF-κB. Moreover, it also protected hyperglycemia-mediated cardiac damage	[111]
Troxerutin	Diabetic cardiomyopathy	Troxerutin, a rat drug, was found to protect against cardiomyopathy by reducing reactive oxygen species levels, NF-κB protein expression, and suppressing phosphorylated forms of AKT, insulin receptor substrate 1, and JNK in a type 2 diabetes model	[137]
Fisetin	Diabetic neuropathy	Fisetin treatment improved MNCV and sciatic NBF deficits in diabetic rats, reducing interleukin-6 and tumour necrosis factor-alpha in sciatic nerves. The therapeutic benefit of fisetin may be through regulation of redox sensitive transcription factors like Nrf2 and NF-κB	[71]
Melatonin	Diabetic neuropathy	Melatonin treatment in animals improved motor nerve conduction velocity and blood flow, reduced NF-κB expression, and reduced proinflammatory cytokines in sciatic nerves. It also modulated the Nrf2 pathway, increased heme oxygenase-1 expression, and strengthened antioxidant defense, potentially reducing NF-κB activation cascade	[76]
Rutin	Diabetic neuropathy	Rutin and nimesulide treatment attenuates oxidative damage in the sciatic nerve, reducing mitochondrial ROS production, inflammatory markers, and Nrf-2/HO-1 expression, making them more effective than streptozotocin alone in DN control rats	[57]
Sulforaphane	Diabetic neuropathy	Sulforaphane improves motor nerve conduction, blood flow, and pain behavior, reduces malondialdehyde levels, activates Nrf2 and its targets, and inhibits NF-κB, thereby reversing deficits in experimental diabetic neuropathy, supporting Nrf2's role in neurons under oxidative stress	[69]