CKD was induced in Sprague-Dawley rats by 5/6 nephrectomy (Nx). Separated groups of 5/6 Nx rats were treated intragastrically with tangeretin (50, 100 or 200 mg/kg bw) or enalapril for 30 days, starting 5 days after the surgery. Elevated TNF-α, nitric oxide (NO) and cytokines-IL-6 and IL-1β with upregulated NF-κB/TNF-α/iNOS signaling 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.

Human colorectal adenocarcinoma cell line, LoVo, and its resistant subline, LoVo/Dx, obtained by prolonged exposure to doxorubicin were cultivated in Ham's F12 medium at 37 deg-C and an atmosphere of 5% CO2 (with addition of 10% fetal bovine serum, L-glutamine, antibiotics, and in the case of loVo/Dx cells, doxorubicin at 100 ng/mL). Cells were seeded in 96-well plates in 75 micro-L of medium and allowed to attach for 60 min at 37 deg-C. An equal volume of medium containing Tangeretin was added, and the incubation was continued for 72 hours. Cytotoxicity was monitored using a sulforhodamine B assay. Tangeretin demonstrated the greatest cytotoxicity among studied compounds in both LoVo, and LoVo/Dx cells with an IC50 range between 20 - 40 microM.