Abstract

Progressive diabetic nephropathy (DN) in diabetes leads to major morbidity and mortality. The major pathological alterations of DN include mesangial expansion, extracellular matrix alterations, tubulointerstitial fibrosis, and glomerular sclerosis. Polygoni avicularis is widely used in traditional oriental medicine and has long been used as a diuretic, astringent, insecticide and antihypertensive. However, to the best of the authors’ knowledge, the effects of the ethanolic extract from rhizome of Polygoni avicularis (ER-PA) on DN have not yet been assessed. The present study aimed to identify the effect of ER-PA on renal dysfunction, which has been implicated in DN in human renal mesangial cells and db/db mice and investigate its mechanism of action. The in vivo experiment was performed using Polygoni avicularis-ethanol soluble fraction (ER-PA) and was administrated to db/db mice at 10 and 50 mg/kg dose. For the in vitro experiments, the human renal mesangial cells were induced by high glucose (HG, 25 mM). The ER-PA group showed significant amelioration in oral glucose tolerance, and insulin resistance index. ER-PA significantly improved the albumin excretion and markedly reduced plasma creatinine, kidney injury molecule-1 and C-reactive protein. In addition, ER-PA significantly suppressed inflammatory cytokines. Histopathologically, ER-PA attenuated glomerular expansion and tubular fibrosis in db/db mice. Furthermore, ER-PA suppressed the expression of renal fibrosis biomarkers (TGF and Collagen IV). ER-PA also reduced the NLR family pyrin domain containing 3 inflammatory factor level. These results suggest that ER-PA has a protective effect against renal dysfunction through improved insulin resistance as well as the inhibition of nephritis and fibrosis in DN.

Highlights

  • Food and water intake were significantly higher in the db/db group compared with the db/m group

  • The nephrin protein and mRNA level significantly increased in the PAL and PAH groups compared with the db/db group (Figure 5B,C; p < 0.01; p < 0.05). These results suggested that PAH can improve kidney damage by upregulating the expression of nephrin, a biomarker of early glomerular damage

  • These levels were significantly higher in db/db mice compared with the db/m mice, the difference between untreated and ER-PAtreated db/m mice was small and the values remained within the normal range

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Summary

Introduction

Diabetic nephropathy is a typical kidney disease that occurs as result of diabetes mellitus [1]. One of the most common complications of diabetes [2], is the most frequent cause of end-stage renal failure [3]. Kidney damage affects various structures of the kidneys and is mainly characterized by an increased deposition of the extracellular matrix (ECM), aggravated glomerular fibrosis, and the overexpression of chemokines, leading to tubulointerstitial damage [4,5]. The consequences involve kidney fibrosis, proteinuria, and kidney inflammation. Diabetic nephropathy is one of the leading

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