Polymethoxyflavone-rich Fraction from Citrus sunki Leaves Alleviates Renal Dysfunction in Mice with Unilateral Ureteral Obstruction

Abstract

Polymethoxyflavones (PMFs) are flavonoid compounds present in citrus plants that are proposed to be advantageous to human health. However, the advantageous effects of PMFs in the context of renal dysfunction are unclear. In this study, we made a PMF-rich fraction (PRF) from the leaves of Citrus sunki Hort ex. Tanaka and identified its components using liquid chromatography and mass spectrometry. We then investigated the effect of PRF-comprising 9 types of PMF-on renal dysfunction induced by unilateral ureteral obstruction (UUO) in mice. Animals were divided into four experimental groups (n = 7 per group): I) sham-operated group (Sham); II) UUO group (UUO); III) UUO + Enalapril 0.1 mg/1 mL (UUO + Enap); IV) UUO + PRF 100 mg/kg/day (UUO + PRF). All mice were orally administered with the drugs once a day from 7 days before UUO to 1 week after UUO. After the experiments were over, serum and tissues were taken for biochemical and histological analysis. PRF promoted the recovery of body weight in the background of UUO. Biochemical and histological analysis revealed that PRF ameliorated UUO-induced renal dysfunction and moderately reversed inflammation and tubulointerstitial fibrosis. Further, PRF inhibited the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), transforming growth factor-beta (TGF-beta), collagen I (Col-I), and collagen IV (Col-IV). These results suggest that PRF improves UUO-induced renal dysfunction by regulating the expression of inflammatory and fibrotic response-related genes.