The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high‑fat diet/streptozotocin‑induced diabetic kidney disease rat model

Abstract

The Chinese decoction compound centella formula (CCF) is clinically effective against diabetic kidney disease (DKD), but the exact mechanism remains unclear. The present study aimed to investigate the effects of CCF on OxInflammation and silent information regulator 1 (SIRT1) levels in rats with streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were divided into CCF, losartan, diabetic control (DC) and normal control (NC) groups (n=7). Except for the NC, all subgroups of rats were fed a high-fat diet for 112 days and received a single intraperitoneal injection of 35 mg/kg STZ on day 29. All rats were sacrificed on day 112. High-performance liquid chromatography was performed to analyse asiaticoside, astragaloside and triptolide levels in CCF (0.3400, 0.0640 and 0.0001 mg/ml, respectively). Fasting blood glucose, urine protein-to-creatinine ratio, serum creatinine and blood urea nitrogen were quantified. Periodic acid Schiff staining, H&E staining and transmission electron microscopy were used to examine kidney pathological changes. The mRNA and protein expression levels of SIRT1 in renal tissues were analysed by reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Oxidative stress was evaluated by measuring the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in renal tissues. TNF-α and NF-κB p65 subunit in renal tissues were assessed for inflammation. Compared with the rats in the NC group, the rats in the DC group exhibited renal injury with proteinuria, decreased expression levels of SIRT1 and SOD (P<0.01) and increased levels of MDA, NOX4, TNF-α and NF-κB p65 (P<0.01). CCF treatment reduced proteinuria (P<0.01), alleviated renal damage, decreased MDA, NOX4, TNF-α and NF-κB p65 levels (P<0.01), increased SOD levels (P<0.05) and increased SIRT1 mRNA and protein expression levels (P<0.01). The present study indicates that CCF effectively protects the kidney from diabetes by inhibiting OxInflammation and upregulating SIRT1.

Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population

“…Growing evidence has implicated the role of chronic inflammation andoxidative stress in the pathogenesis of DKD ( 49 , 50 ), and inflammation and oxidative stress may be considered as a hub of the different pathogenic pathways that contribute to DKD ( 51 ). The imbalance of of several pro-and anti-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C reactive protein (CRP), neutrophils, lymphocytes, and platelet cells, and pro- and anti-oxidants, such as superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG-8-hydroxy-2′-deoxyguanosine (8-OHdG) have previously been reported to be related to the development of DKD ( 4 , 5 , 49 , 52 , 53 ). Hb, an iron-containing protein in blood, may serve as a nitricoxide scavenger, and its ability of Hb to bind the main low-molecular-weight thiol of the cell glutathione, both covalently and noncovalently, is not only an important part of the antioxidant protection of red blood cells, but also affects its affinity for oxygen in both cases ( 54 , 55 ).…”

Translation Animal Models of Diabetic Kidney Disease: Biochemical and Histological Phenotypes, Advantages and Limitations

“…after being fed HFD or HSuHF for 4–6 weeks, and almost all of these rats develop significant hyperglycemia and proteinuria after induction, with early renal pathology such as glomerular hypertrophy, mesangial expansion, extracellular matrix (ECM) deposition and mild glomerulosclerosis. 76–79 In male B6 mice, T2D-DKD can be induced by HFD-feeding with a single low-dose STZ (40 mg/kg, i.p. ), or medium-dose STZ (100–120 mg/kg, i.p.…”