P0170ETHANOL EXTRACT OF LIRIODENDRON CHINENSE(HEMSL.) SARG BARKS ALLEVIATES HYPERURICEMIC NEPHROPATHY VIA MEDIATING RENAL FIBROSIS AND INFLAMMATION

Abstract

Abstract Background and Aims The barks of Liriodendron Chinense (Hemsl.) Sarg is used in folk for expelling “wind and dampness”, alleviating rheumatic arthralgia in traditional Chinese medicine. The aim of the study was to evaluate the protective effect of ethanol extract of the barks of Liriodendron Chinense (Hemsl.) Sarg (EELC) in a mouse model of hyperuricemic nephropathy (HN) and the mechanisms involved. Method EELC at a respective dose of 250 mg/kg/d or 500 mg/kg/d were orally administered to HN mice induced by a mixture of adenine (160 mg/kg/d)/potassium oxonate (2.4 g/kg/d) for 21 days. At the end of the treatment, serum uric acid, kidney functions (serum creatinine, BUN and urine microalbumin), 24-h urine uric acid excretion, as well as kidney pathological changes were investigated by biochemical assay, histopathological score, immunofluorescence and histochemistry, RT-PCR, and western blotting analysis. Results Oral administration of EELC to HN mice lowered serum uric acid, improved renal functions and attenuated renal fibrosis, especially the high-dose of EELC. EELC treatment also inhibited the activation of NF-κB, ASK1/JNK/c-Jun, JAK2/STAT3 signaling pathways and reduced the release of pro-inflammatory cytokine TNF-α in the kidneys of HN mice. Furthermore, EELC remarkably increased urine uric acid excretion of HN mice, which may be achieved by the upregulation of organic anion transporter 1 (OAT1), OAT3 and ATP-binding cassette subfamily G member 2 (ABCG2) proteins. Conclusion EELC alleviated the progression of HN by suppressing the activation of NF-κB, ASK1/JNK/c-Jun and JAK2/STAT3 signaling pathway, reducing the infiltration of inflammatory factors and uric acid accumulation in the kidney. Figure Date are represented as the mean ± SD. *p<0.05,**p<0.01,***p<0.001, ****p<0.0001 vs. control, §p <0.05, §§p<0.01, §§§p<0.001,§§§§p<0.0001 vs. model.