Lespedeza bicolor Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads to morphological and functional changes in kidney. A previous study showed a protective effect of Lespedeza bicolor extract (LBE) on endothelial dysfunction induced by methylglyoxal glucotoxicity. We aimed to investigate whether LBE ameliorated renal damage through regulation of NLRP3 inflammasome-dependent hyper-inflammation in T2DM mice. After T2DM induction by a high fat diet and low dose of streptozotocin (30 mg/kg), the mice were administered with different dosages of LBE (100 or 250 mg/kg/day) by gavage for 12 weeks. LBE supplementation ameliorated kidney dysfunction demonstrated by urine albumin-creatinine at a low dose and plasma creatinine, blood urea nitrogen (BUN), and glomerular hypertrophy at a high dose. Furthermore, a high dose of LBE supplementation significantly attenuated renal hyper-inflammation associated with NLRP3 inflammasome and oxidative stress related to nuclear factor erythroid 2-related factor 2 (Nrf-2) in T2DM mice. Meanwhile, a low dose of LBE supplementation up-regulated energy metabolism demonstrated by phosphorylation of adenosine monophosphate kinase (AMPK) and Sirtuin (SIRT)-1 in T2DM mice. In conclusion, the current study suggested that LBE, in particular, at a high dose could be used as a beneficial therapeutic for hyperglycemia-induced renal damage in T2DM.

Evaluation of Neutrophil/Lymphocyte Ratio, Low-Density Lipoprotein/Albumin Ratio, and Red Cell Distribution Width/Albumin Ratio in the Estimation of Proteinuria in Uncontrolled Diabetic Patients

“…Chronic hyperglycemia in diabetes promotes a pro-inflammatory state, leading to increased neutrophil counts and subsequent tissue inflammation [ 14 ]. One of the potential mechanisms underlying the association between NLR and proteinuria could be that this chronic inflammation can contribute to immune dysfunction, altered responses to inflammation, renal damage, and ultimately proteinuria [ 15 , 16 ]. Immune dysfunction, characterized by altered neutrophil and lymphocyte counts, may disrupt the immune response against renal injury, thereby facilitating the development of proteinuria [ 16 ].…”

Effect of Quamoclit angulata Extract Supplementation on Oxidative Stress and Inflammation on Hyperglycemia-Induced Renal Damage in Type 2 Diabetic Mice

“…The previous study reported by our group found that the Lespedeza bicolor extract (LBE) containing polyphenolic compounds such as quercetin, genistein, daidzein, and naringenin has shown to exert antioxidant and anti-inflammatory effects accompanied by upregulation of the AMPK-SIRT1 pathway in the same diabetic model [52]. The current findings supported that QAE at much lower concentrations compared to LBE and other plant extracts has shown antidiabetic effects through regulation of the AMPK-SIRT related mechanism as shown in LBE treated diabetic mice [52]. Moreover, QAE supplementation attenuated pro-fibrosis as well as apoptosis in the diabetic group, which was not shown in LBE treatment groups.…”

Ferroptosis: new insight into the mechanisms of diabetic nephropathy and retinopathy

“…Emerging evidence suggests a strong link between diabetic complications and ferroptosis. Hyperglycemia leads to the overproduction of ROS and induces oxidative stress in various organs of diabetic patients (9). High glucose could cause an overload of iron, and iron dysregulation induces the production of ROS and promotes oxidative stress, which leads to ferroptosis finally (10).…”