Table 3.

The role of NF-κB in DNP.

Molecular pathway	Remark	Ref
NF-κB	The levels of NF-KB p65, p–NF–KB p65, IKB-α, VEFG, IL-8, α-SMA, and FN were increased, and epigallocatechin-3-gallate decreased hypermethylation of ACTN4 in HPC cells by restoring ACTN4 expression and downregulating DNMT1 expression	[217]
TRIM29/NF-κB/NLRP3	TRIM29 silencing significantly reduces podocyte damage from HG treatment, resulting in reduced desmin and nephrin expression. It also prevents HG-induced pyroptosis, indicating TRIM29 promotes pyroptosis via the NF-κB pathway. TRIM29 interacts with IκBα, leading to NF-κB activation	[218]
SphK1/S1P/NF-κB	BA protects against DN by reducing inflammation, oxidative stress, and apoptosis through the SphK1/S1P/NF-κB pathway. It reduces serum glucose concentration, blood lipid levels, kidney functions, and histopathological changes in kidney tissues. Overexpression of SphK1 or S1P could reverse these effects	[219]
NF-κB	GA treatment reduces diabetes-induced renal injury by downregulating miR-125b, NF-кB, TNF-α, IL-1β, and IL-10 in renal tissue, while upregulating IL-10, miR-200a, and Nrf2. It also downregulates ACE1, AT1R, and NOX2, demonstrating its antioxidant and anti-inflammatory properties	[220]
NF-κB/NLRP3	4-PBA inhibited ER stress, alleviating HG-induced pyroptosis in MDCK cells. BYA 11–7082 reduced NLRP3 and GSDMD gene and protein expression, indicating ER stress contributes to pyroptosis in canine type 1 DNP	[221]
NF-κB/NLRP3	Breviscapine treatment significantly improved renal function in diabetic mice by increasing podocyte viability, inhibiting HG-induced cell apoptosis, and ameliorating HG-induced podocyte injury. It also decreased α-SMA expression, increased podocin and synaptopodin expression, and inhibited NF-κB signaling activation, thereby reducing pyroptosis	[222]
TLR4/NF-κB/NLRP3	Sanziguben polysaccharide reduced urine albumin, insulin resistance, creatinine, and blood urea nitrogen levels in diabetic mice, mitigated renal damage, and regulated gut microbiota. It lessened lipopolysaccharides levels and inhibited TLR4/NF-κB/NLRP3 pathway expression, alleviating DN	[223]
SNHG16/NF-κB	Diabetes-induced kidney injury (DRI) can be reduced by silencing SNHG16 and TLR4, which are upregulated in diabetic conditions. SNHG16 silencing decreases cytokine secretion, ROS, MDA, and fibrosis, while increasing SOD and GSH. TLR4 knockdown alleviates HG-induced renal injuries by suppressing RAS and NF-κB-mediated activation of NLRP3 inflammasomes	[224]
AT1R/CK2/NF-κB	GPS treatment improves glycolipid metabolism disorder, renal dysfunction, and TIF in mice by reversing abnormal EMT marker protein expressions, inhibiting angiotensin-1 receptor (AT1R) and CK2α protein expressions, and activating the NF-κB pathway	[225]
MAPK/NF-κB	Sclareol treatment in diabetic mice reduced renal dysfunction, fibrosis, and inflammatory cytokine levels by inhibiting MAPKs and NF-κB activations, preventing high glucose-induced fibrosis and inflammatory responses, making it a promising agent for preventing DN progression	[226]
PI3K/Akt/NF-κB	Fufang Zhenzhu Tiaozhi treatment can reduce SUA, SCr, and Cys C levels, improve renal histology, and attenuate inflammasome activation, collagen deposition, and uric acid transporter imbalance in HN mice. It also reduces AKT and p65 phosphorylation, thus preventing renal injury, inflammation, and fibrosis	[227]
CircTLK1/miR-126-5p/miR-204-5p	CircTLK1 knockdown reduced inflammation, oxidative stress, and ECM accumulation in HG-induced DN by blocking the AKT/NF-κB pathway, providing a new understanding of DN pathogenesis	[214]
TLR4/NF-κB	High glucose exposure caused mitochondrial dysfunction, oxidative stress, and decreased PRDX6 expression in HK-2 cells. PRDX6 elevation increased cell viability but reduced apoptosis and inflammation. It also inhibited HG-induced TLR4/NF-κB activation. However, CRX-527 or PMA reversed these effects	[228]
NF-κB	Isobavachalcone consumption can benefit the kidney (DN) by preventing STZ-induced apoptosis in vivo and blocking high glucose-induced growth inhibitory effects in human renal glomerular endothelial cells. This action may be correlated with the modulation of the NF-κB pathway	[229]
NF-κB	Tissue homogenate of the kidney extracted from LCZ696 and valsartan treated diabetic rats revealed a substantial reduction in the levels of inflammatory markers such as TNF-α, IL-1β, IL-6, NF-kB and sufficient restoration of anti-oxidant enzyme levels. LCZ696 has shown promising therapeutic potential in reducing DN progression by inhibiting inflammation, oxidative stress, and glomerulosclerosis	[230]
NF-κB	Tetrahydrocannabinol (TA) activated Nrf2 signaling, increased antioxidant enzyme expression, inhibited NF-κB, and downregulated proinflammatory cytokine expressions. It also increased nephrin and podocin protein expression, while reducing COL-III and FN protein expression	[231]
NF-κB	F-GAL and FS-AE are effective treatments for Type 1 Diabetes in diabetic rats. They improve kidney and liver structure, reduce reactive oxygen species, and improve serum levels of ALT, AST, albumin, and creatinine. However, they increase hepatic and renal superoxide dismutase, leading to increased Nrf2 transcription and translation	[232]
TLR9/NF-κB	TLR9 expression is upregulated in kidneys of mice and MCs under hyperglycemic conditions. Knockdown reduces NF-kB viability and NLRP3 inflammasome. TLR9 inhibition alleviates inflammation and apoptosis, but reverses by betulinic acid. Depleted TLR9 levels reduce inflammation and glomerular damage	[233]
SOCS2/TLR4/NF-κB	SOCS2 is down-regulated in renal tissues of DN patients and rats, while TLR4 and NF-κB are up-regulated. Ad-SOCS2 infection alleviates STZ-induced renal injury and pathological changes, while SOCS2 overexpression reduces apoptosis, inflammatory cytokine expression and inactivates the TLR4/NF-κB pathway	[234]
NF-κB	Vanillic acid showed a significant ameliorative impact on diabetic nephropathic rats due to its powerful free radical scavenging property, which suppressed the upregulation of NF-κB, TNF-α, COX-2, and upregulation of Nrf-2 proteins in renal tissue, thereby reducing inflammation and promoting kidney health	[235]