Abstract
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood.MethodsThe DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide.ResultsBerberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes.ConclusionsBerberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.
Highlights
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients
BBR ameliorated renal injury in STZ‐induced DN rat model To determine the protective effect of BBR in DN, the indexes associated with kidney function, including fasting blood glucose levels, body weight, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured
The results showed that STZ injection resulted in a significant increase in fasting blood glucose level (Fig. 1a), kidney/ body weight (Fig. 1c), 24 h-urinary protein level (Fig. 1d), serum creatinine level (Fig. 1e) and blood urea nitrogen
Summary
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. Diabetic nephropathy (DN) is a major complication in patients with either type 1 or type 2 diabetes mellitus and one of the leading causes of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients [1]. It is characterized by microalbuminuria, glomerular and tubular epithelial hypertrophy, excessive accumulation of extracellular matrix (ECM) protein, Zhu et al Biol Res (2018) 51:9 tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 [6]. The underlying mechanism of the renoprotective effect of BBR on DN remains to be further explored
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