Protective Effects of Ethanolic Extract from Rhizome of Polygoni avicularis against Renal Fibrosis and Inflammation in a Diabetic Nephropathy Model

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.

Bibliometric Analysis and Visualization of Research Progress in the Diabetic Nephropathy Field from 2001 to 2021

“…There have been over 18,000 DN-related manuscripts published since the beginning of the 21 st century corresponding to a diverse array of topics including DN-related drug therapy [ 24 – 26 ], the pathology and pathophysiology of DN [ 27 ], the diagnosis of DN [ 28 , 29 ], the etiology of DN [ 30 , 31 ], and the epidemiology of DN [ 32 , 33 ]. Given the complexity and density of information published in this field over the past two decades, there is a clear need for a systematic and objective approach to surveying DN-related research directions.…”

“…During the period from 2016 to 2021, the results of both biclustering analyses and SNAs indicated that plant extract-based drugs and sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as promising directions for the drug-based treatment of DN. The Polygonaceae-derived Polygonum aviculare L. (PA) extract, for example, has been reported to alleviate DN through the amelioration of renal tubular fibrosis and glomerulosclerosis [ 26 ]. Ranunculus ternatus Thunb (RTT) was shown to suppress fibrotic and inflammatory responses, thereby protecting against DN-related pathogenesis [ 24 ].…”

“…Mesangial cells can modulate DN pathogenesis through the shaping of fibrotic, inflammatory, and oxidative stress activity [ 54 ]. Drugs derived from plants can ameliorate mesangial cell metabolism, thereby effectively treating DN [ 26 ]. Notably, miRNAs, signal transduction pathways, and mesangial cells are all interconnected with one another such that miRNAs can modulate key signaling pathways to modulate the metabolic activity of mesangial cells, thus affecting the development and severity of DN [ 55 ].…”

Role of NOD-Like Receptors in a Miniature Pig Model of Diabetic Renal Injuries

“…Several evidences have shown that TGF- β is an important mediator of diabetic nephropathy. In rodent diabetes models, the levels of TGF- β 1 mRNA and protein in the glomeruli and renal tubules are increased [ 32 , 33 ]. In the TGF- β /Smad signaling pathway, TGF- β binds to the T β RII receptor and phosphorylates it and then forms a TGF- β complex by binding to T β RІ receptor.…”

Ellagic Acid Inhibits TGFβ1/Smad-Induced Renal Fibrosis in Diabetic Kidney Injury

“…Among the pathological changes of diabetic nephropathy, glomerulosclerosis, tubular inflammation, tubular atrophy, and inter-tubular fibrosis are common (3). Renal fibrosis seen in diabetic nephropathy may damage tissue and thus organ function and finally lead to kidney failure (4,5). Renal fibrosis is associated with transforming growth factor β (TGFβ) / suppressor of mothers against decapentaplegic (Smad) signaling.…”