Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy

Yuan-Ye Qiu; Li-Qin Tang; Wei Wei

doi:10.1016/j.mce.2017.01.009

Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy

Mol Cell Endocrinol. 2017 Mar 5:443:89-105. doi: 10.1016/j.mce.2017.01.009. Epub 2017 Jan 10.

Authors

Yuan-Ye Qiu¹, Li-Qin Tang², Wei Wei³

Affiliations

¹ Institute of Clinical Pharmacology, Anhui Medical University, 81#Mei-shan Road, Hefei 230032, Anhui, People's Republic of China; Department of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, 17# Lu-jiang Road, Hefei 230001, Anhui, People's Republic of China. Electronic address: qiuyuanye1201@163.com.
² Department of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, 17# Lu-jiang Road, Hefei 230001, Anhui, People's Republic of China. Electronic address: tulcyl@vip.sina.com.
³ Institute of Clinical Pharmacology, Anhui Medical University, 81#Mei-shan Road, Hefei 230032, Anhui, People's Republic of China. Electronic address: wwei@ahmu.edu.cn.

PMID: 28087385
DOI: 10.1016/j.mce.2017.01.009

Abstract

In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine. In vitro, berberine inhibited mesangial cell proliferation. Cells treated with berberine showed reduced levels of AGEs, accompanied by decreased RAGE, p-PKC and TGF-β1 levels soon afterwards. Berberine exhibited renoprotective effects in diabetic nephropathy rats, and the molecular mechanism was associated with changes in the levels and regulation of the AGEs-RAGE-PKC-β-TGF-β1 signaling pathway.

Keywords: AGEs-RAGE axis; Berberine; Diabetic nephropathy; Glomerulus mesangial cell; Renoprotection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Berberine / pharmacology
Berberine / therapeutic use*
Blood Glucose / metabolism
Body Weight / drug effects
Cell Proliferation / drug effects
Diabetic Nephropathies / blood
Diabetic Nephropathies / drug therapy*
Diabetic Nephropathies / pathology*
Diabetic Nephropathies / physiopathology
Down-Regulation / drug effects
Fasting / blood
Glucose / pharmacology
Glycation End Products, Advanced / blood
Glycation End Products, Advanced / metabolism*
Kidney / drug effects
Kidney / pathology
Kidney / physiopathology
Kidney Function Tests
Male
Mesangial Cells / drug effects
Mesangial Cells / metabolism*
Mesangial Cells / pathology
Phosphorylation / drug effects
Protective Agents / pharmacology
Protective Agents / therapeutic use*
Protein Kinase C beta / metabolism
Rats, Sprague-Dawley
Receptor for Advanced Glycation End Products / metabolism*
Signal Transduction* / drug effects
Streptozocin
Transforming Growth Factor beta1 / metabolism

Substances

Blood Glucose
Glycation End Products, Advanced
Protective Agents
Receptor for Advanced Glycation End Products
Transforming Growth Factor beta1
Berberine
Streptozocin
Protein Kinase C beta
Glucose