Hong-Guang Jin

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.

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Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-β (TGF-β)/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-κB) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.