Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy

Abstract

Diabetes mellitus (DM) is a high-impact disease commonly characterized by hyperglycemia, inflammation, and oxidative stress. Diabetic nephropathy (DN) is a common diabetic microvascular complication and the leading cause of chronic kidney disease worldwide. This study investigates the protective effects of the synthetic flavonoid hidrosmin (5-O-(beta-hydroxyethyl) diosmin) in experimental DN induced by streptozotocin injection in apolipoprotein E deficient mice. Oral administration of hidrosmin (300 mg/kg/day, n = 11) to diabetic mice for 7 weeks markedly reduced albuminuria (albumin-to-creatinine ratio: 47 ± 11% vs. control) and ameliorated renal pathological damage and expression of kidney injury markers. Kidneys of hidrosmin-treated mice exhibited lower content of macrophages and T cells, reduced expression of cytokines and chemokines, and attenuated inflammatory signaling pathways. Hidrosmin treatment improved the redox balance by reducing prooxidant enzymes and enhancing antioxidant genes, and also decreased senescence markers in diabetic kidneys. In vitro, hidrosmin dose-dependently reduced the expression of inflammatory and oxidative genes in tubuloepithelial cells exposed to either high-glucose or cytokines, with no evidence of cytotoxicity at effective concentrations. In conclusion, the synthetic flavonoid hidrosmin exerts a beneficial effect against DN by reducing inflammation, oxidative stress, and senescence pathways. Hidrosmin could have a potential role as a coadjutant therapy for the chronic complications of DM.

The Synthetic Flavonoid Hidrosmin Improves Endothelial Dysfunction and Atherosclerotic Lesions in Diabetic Mice

“…ApoE KO mice (14–16 weeks old males; Jackson Laboratory, Bar Harbor, ME, USA) were made diabetic by two daily consecutive injections of STZ (125 mg/kg/day, intraperitoneally; S0130, Sigma-Aldrich, St. Louis, MO, USA) dissolved in 10 mmol/L citrate buffer pH 4.5 [ 32 , 33 ]. After 2 weeks, mice with overt diabetes (glucose > 350 mg/dL) were randomized to receive 300 mg/kg/day of hidrosmin in the drinking water (D group, n = 11) or tap water (D + H group, n = 7) for 7 weeks, based on our previous study [ 30 ].…”

“…Besides the treatment of chronic venous insufficiency, several preclinical studies have established that diosmin-containing medicinal products protect against hepatic, pulmonary, neurological, gastrointestinal, myocardial and renal injuries [ 23 , 24 , 25 , 29 ]. In this line, our previous study was the first to demonstrate a favorable effect of hidrosmin on the reduction of renal damage in diabetic mice [ 30 ]; however, the mechanisms and actions of the synthetic flavonoid in macrovascular complications of diabetes have not been scrutinized.…”

Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination

“…With the rapidly increasing incidence worldwide, it is estimated that the number of diabetic patients will reach 300 million by 2025 [ 2 ]. Among them, about one-third of diabetes later developed into diabetic nephropathy, which is the main cause of end-stage renal disease (ESRD) [ 3 ]. At present, there is no clear etiology and pathogenesis of DN, which leads to limitations in the clinical treatment of DN [ 3 ].…”

“…Among them, about one-third of diabetes later developed into diabetic nephropathy, which is the main cause of end-stage renal disease (ESRD) [ 3 ]. At present, there is no clear etiology and pathogenesis of DN, which leads to limitations in the clinical treatment of DN [ 3 ].…”

The analysis of risk factors for diabetic kidney disease progression: a single-centre and cross-sectional experiment in Shanghai

“… 12 It has been reported that there are high concentrations of inflammatory cells in the glomeruli and tubulointerstitium of diabetic kidneys, as well as the overexpression of chemokines, cytokines and adhesion molecules, and inflammation has become a focus of DKD development. 13 We will also focus on the relationship between diabetic nephropathy and inflammation in this study.…”