Demethylzeylasteral ameliorates inflammation in a rat model of unilateral ureteral obstruction through inhibiting activation of the NF-κB pathway

Abstract

The present study investigated the pharmacody-namic role and therapeutic mechanism of demethylzeylasteral in the suppression of inflammation in a rat model of unilateral ureteral obstruction and reduction in nuclear factor (NF)- κB pathway activity. The rats in the unilateral ureteral obstruction model were treated with 30-120 mg/kg demethylzeylasteral for 8 weeks. The activities of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and caspase-3/9, and the protein expression levels of cyclooxygenase (COX)-2 and intercellular adhesion molecule-1 (ICAM-1) and NF-κB p65 were analyzed using ELISA kits and western blot analyses, respectively. Compared with the rats in the unilateral ureteral obstruction model group, demethylzeylasteral treatment markedly inhibited the increased concentrations of serum creatinine and blood urea nitrogen, urinary protein/creatinine ratio, and concentrations of high-density lipoprotein and low-density lipoprotein cholesterol, and prevented kidney damage. In addition demethylzeylasteral inhibited the levels of TNF-α andIL-6 and suppressed the protein expression levels of COX-2 and ICAM-1 in the kidneys of the rats in the unilateral ureteral obstruction model. Demethylzeylasteral also significantly suppressed the protein expression of NF-κB p65. The results of the present study suggested that demethylzeylasteral unilateral ureteral obstruction and inhibited inflammation via inhibiting the activation of COX-2, ICAM-1 and NF-κB p65, and suppressing the activities of caspase-3/9 in rats with unilateral ureteral obstruction.