Tangeretin ameliorates renal failure via regulating oxidative stress, NF-κB–TNF-α/iNOS signalling and improves memory and cognitive deficits in 5/6 nephrectomized rats

Abstract

Chronic kidney disease (CKD) is a significant global health concern with limited treatment options. Oxidative stress and inflammatory responses have been implicated in the pathology of CKD. Patients with CKD are frequently affected with neurological complications that affect both the central and peripheral nervous system. Identification of effective treatment strategies are of much clinical value in the therapy of CKD. Tangeretin, a plant-derived flavonoid has been described to retain extensive pharmacological properties. In the present study, we explored whether tangeretin exerted protective effects in 5/6 nephrectomized rats. CKD was induced in Sprague-Dawley rats by 5/6 nephrectomy (Nx). Separate groups of 5/6 Nx rats were treated with tangeretin (50, 100 or 200 mg/kg b.wt.) or enalapril for 30 days (starting 5 days after surgery for 35 days). Control animals were not subjected to Nx nor were treated with tangeretin or enalapril. Renal dysfunction, as evinced by raised serum urea, serum creatinine, proteinuria, and histological alterations were significantly reduced by tangeretin and enalapril treatment. 5/6 Nx animals exhibited raised levels of malondialdehyde (MDA) and reactive oxygen species. Elevated TNF-α, nitric oxide (NO) and cytokines-IL-6 and IL-1β with upregulated NF-κB/TNF-α/iNOS signalling pathways were effectively down-regulated by tangeretin. Cognitive disturbances and memory impairments observed in Nx rats were substantially improved by tangeretin. Collectively, the experimental data indicate that the anti-oxidant and anti-inflammatory effects of tangeretin effectively improved renal function and reduced the cognitive and memory impairments in CKD-induced animals.

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

“…It was also indicated that tangeretin could cure nephrectomy-induced chronic kidney injury and the associated memory impairment, which are closely correlated with inflammatory responses, by reducing the levels of inflammatory mediators, NO, IL-1β, IL-6 and TNF-α through regulating IκBα, IKKα, IKKβ and iNOS phosphorylation as well as NF-κB p65 expression. In brief, tangeretin can specifically act on NF-κB/TNF-α/iNOS signaling pathways when dealing with kidney-related injuries (Wu et al, 2018).…”

Behavioral Changes During Development of Chronic Kidney Disease in Rats

“…Cognitive decline is one of the most common neurological symptoms in CKD patients (12-15, 17, 30). Numerous experiments have confirmed deficit in spatial- (23,45), recognition- (21,42,(45)(46)(47), as well as aversive-related memory (46)(47)(48) in CKD animals. On the contrary, there are also some experiments which failed to show memory-impairing effect of CKD (24,49).…”

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

“…The NF-κB signaling pathway is critical for induction of various in ammation-related cytokines and mediators, including inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP) proteins, TNF-α, and IL-1β. [20,21] However, molecular mechanisms involved in macrophage polarization remain unknown.…”