Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models

Abstract

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Renal protective effect of ellipticine against streptozotocin induced diabetic nephropathy in rats via suppression of oxidative stress and inflammatory mediator

“…DN is induced by the multiple mechanisms, and the researcher chooses the drugs that have the multiple pharmacological action 34,35 . DM led to hypercholesterolemia, hypertriglyceridemia, and fatty liver.…”

Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease

“…A meta-analysis for DKD found that Keluoxin capsule improved the levels of serum creatinine and lipid (126). A STZ-induced rat model was used by some researchers to demonstrate the protective effects of Keluoxin capsule in vivo, they found Keluoxin capsule regulated autophagy in podocytes via increasing the expression of LC3-II and p62 proteins (12).…”

The critical role of dysregulated autophagy in the progression of diabetic kidney disease

“…In the ATG5 knockout mouse model and proximal tubular epithelial cells model, defective autophagy downregulated lysosomal biogenesis and promote the accumulation of AGEs, leading to DKD progression ( Takahashi et al, 2017 ). In a study using STZ-induced Sprague-Dawley rats after high-glucose and high-fat model, the drug Keluoxin improved biochemical indicators, reduce podocyte damage and modulate lysosomal function in DKD rats, mitigating the progression of DKD ( Yang X. et al, 2021 ). In a separate study, a group of STZ-induced male BALB/c mice were injected with mesenchymal stem cells (MSCs) via tail vein while primary MSCs were extracted from BALB/c mice for culture and then transfected with TFEB RNA.…”