Diosmetin Attenuates Akt Signaling Pathway by Modulating Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB)/Inducible Nitric Oxide Synthase (iNOS) in Streptozotocin (STZ)-Induced Diabetic Nephropathy Mice

Abstract

BackgroundWe evaluated the nephroprotective effect of diosmetin in streptozotocin (STZ)-induced diabetic nephropathy (DN) mice.Material/MethodsDiabetes was induced by injecting STZ (50 mg/kg) i.p. for 5 days. Biochemical parameters, such as fasting blood glucose, creatinine, BUN in the serum, and albumin in the urine, were determined in STZ-induced DN mice after the 8th week of STZ administration. The level of inflammatory mediators in the serum and oxidative stress parameters in the tissue homogenate was estimated in STZ-induced DN mice. Expressions of Akt, NF-κB, and iNOS in the tissue homogenate were assessed by Western blot analysis.ResultsOur data reveal that treatment with diosmetin significantly reduces the fasting blood glucose (FBG), serum creatinine, and blood urea nitrogen (BUN) in the serum and albumin in urine compared to the negative control group. Treatment with diosmetin attenuated the altered level of oxidative stress parameters and inflammatory cytokines in the STZ-induced DN mice. Expression of Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was significantly reduced and inducible nitric oxide synthase (iNOS) was enhanced in the tissue homogenate of diosmetin-treated mice compared to the negative control group. Data from immunohistochemical analysis suggest that the expressions of NF-κB was significantly reduced in tissues of the diosmetin-treated group compared to the negative control group.ConclusionsOur study shows that diosmetin protects against renal injury in STZ-induced diabetic nephropathy mice by modulating the Akt/NF-κB/iNOS signaling pathway.

Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

“…Diosmetin treatment caused a significant decrease in the levels of inflammatory cytokines in the serum of streptozotocin (STZ)‐induced diabetic nephropathy mice. The anti‐inflammatory effect of diosmetin was mediated by the Akt/NF‐κB/iNOS signaling pathway (Jiang, Liu, Zhou, Liu, & Liu, ). Diosmetin suppressed LPS/D‐galactosamine (D‐GalN)‐induced production of inflammatory mediators and cytokines, for example, iNOS, prostaglandin E2, cyclooxygenase‐2, TNF‐α, IL‐1β, and IL‐6, which was regulated by NF‐κB and mitogen‐associated protein kinases (MAPKs) signaling pathways (Yang et al, ).…”

Eriodictyol inhibits high glucose‐induced extracellular matrix accumulation, oxidative stress, and inflammation in human glomerular mesangial cells

“…Several studies have indicated that Akt/NF‐κB signaling pathway is implicated in the pathogenesis of DN and might be a therapeutic target for DN. For instance, diosmetin protects against renal injury in STZ‐induced DN by modulating the Akt/NF‐κB/iNOS signaling pathway in mice (Jiang, Liu, Zhou, Liu, & Liu, ). Andrographolide ameliorates DN by attenuating hyperglycemia‐mediated renal oxidative stress and inflammation via inhibiting the Akt/NF‐κB pathway in mice (Ji et al, ).…”

Polysulfide and Hydrogen Sulfide Ameliorate Cisplatin-Induced Nephrotoxicity and Renal Inflammation through Persulfidating STAT3 and IKKβ

“…At the end of animal experiments, the serum samples were collected and the serum BUN and creatinine levels were measured to evaluate kidney function by using commercially available kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, China) in accordance with the manufacturer’s protocols [ 29 , 75 ]. The absorbance for serum BUN was analyzed at 640 nm by a microplate reader.…”