Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway

Abstract Background 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. However, the action mechanism of BBR in...

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Autores principales: Zhu,Liping, Han,Jiakai, Yuan,Rongrong, Xue,Lei, Pang,Wuyan
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2018
Materias:
Berberine
Streptozotocin
Diabetic nephropathy
Podocytes
TLR4/NF-κB pathway
Inflammatory response
Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100208
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spelling oai:scielo:S0716-976020180001002082018-06-25Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathwayZhu,LipingHan,JiakaiYuan,RongrongXue,LeiPang,Wuyan Berberine Streptozotocin Diabetic nephropathy Podocytes TLR4/NF-κB pathway Inflammatory response Abstract Background 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. However, the action mechanism of BBR in DN remains to be fully understood. Methods The 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. Results Berberine 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. Conclusions Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.51 20182018-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100208en10.1186/s40659-018-0157-8
institution Scielo Chile
collection Scielo Chile
language English
topic Berberine
Streptozotocin
Diabetic nephropathy
Podocytes
TLR4/NF-κB pathway
Inflammatory response
spellingShingle Berberine
Streptozotocin
Diabetic nephropathy
Podocytes
TLR4/NF-κB pathway
Inflammatory response
Zhu,Liping
Han,Jiakai
Yuan,Rongrong
Xue,Lei
Pang,Wuyan
Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
description Abstract Background 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. However, the action mechanism of BBR in DN remains to be fully understood. Methods The 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. Results Berberine 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. Conclusions Berberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.
author Zhu,Liping
Han,Jiakai
Yuan,Rongrong
Xue,Lei
Pang,Wuyan
author_facet Zhu,Liping
Han,Jiakai
Yuan,Rongrong
Xue,Lei
Pang,Wuyan
author_sort Zhu,Liping
title Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
title_short Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
title_full Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
title_fullStr Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
title_full_unstemmed Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway
title_sort berberine ameliorates diabetic nephropathy by inhibiting tlr4/nf-κb pathway
publisher Sociedad de Biología de Chile
publishDate 2018
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100208
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AT hanjiakai berberineamelioratesdiabeticnephropathybyinhibitingtlr4nf954bpathway
AT yuanrongrong berberineamelioratesdiabeticnephropathybyinhibitingtlr4nf954bpathway
AT xuelei berberineamelioratesdiabeticnephropathybyinhibitingtlr4nf954bpathway
AT pangwuyan berberineamelioratesdiabeticnephropathybyinhibitingtlr4nf954bpathway
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