Effects of triperygium wilfordii polyglucoside on nuclear factor-κB signaling pathway in rats with diabetic nephropathy

Abstract

Objective To investigate the effects of different doses of triperygium wilfordii polyglucoside (TWP) on the nuclear factor-κB signaling pathway in rats with diabetic nephropathy (DN). Methods A total of 60 Sprague-Dawley (SD) rats were seleted. DN rats model were established by high-glucose and high fat diet, in combination with streptozotocin injection from tail vein. DN rats were divided into diabetic normal control group (DNC group, n=8), low dose of TWP group(L-TWP group, 3 mg·kg-1·d-1, n=8) group, median dose of TWP group(M-TWP group, 6 mg·kg-1·d-1, n=8), and high dose of TWP group (H-TWP group, 9 mg·kg-1·d-1, n=10) according to the random number table method. Ten healthy rats were used as control group. After 8 weeks of intervention, body weight(BW), kidney weight/body weight(KW/BW), urine microalbumin(UMA), blood glucose, liver function and renal function were examined. HE staining was used to observe the changes of kidney morphology. Immunohistochemical method, q-PCR and Western blotting were used to analyze the location and expression level of nuclear factor-κB, intercellular adhesion molecule-1(ICAM-1) and interleukin-6(IL-6). The effects of different doses of TWP on the expression of nuclear factor-κB, ICAM-1 and IL-6 in rats with DN. Results TWP therapy decreased UMA but did not affect BW, KW/BW, liver function and renal function. TWP also down-regulated the expression of nuclear factor-κB, ICAM-1, IL-6 mRNA (tNuclear factor-κB=8.89-16.88, tICAM-1=9.56-11.67, tIL-6=10.16-25.78, all P<0.05) as well as the protein level (tNuclear factor-κB=9.87-17.38, tICAM-1=8.54-16.95, tIL-6=9.76-20.18, all P<0.05) in dose-dependent manner; the effects were robust in L-TWP and H-TWP group (all P<0.05). Conclusion TWP suppresses inflammatory signaling pathways of nuclear factor-κB in a dose-dependent manner. Key words: Triperygium wilfordii polyglucoside; Diabetic nephropathy; Nuclear factor-κB; Intercellular adhesion molecule-1; Interleukin-6