title: Matrine ameliorates adriamycin-induced nephropathy in rats by enhancing renal function and modulating Th17/Treg balance.
abstract: Matrine (MAT) is an active alkaloid extracted from Radix Sophora flavescens. The present study was to investigate whether MAT could effectively treat Adriamycin-induced nephropathy (AIN). AIN was induced in rats using a single injection of Adriamycin (ADR). Renal interleukin-6 (IL-6), IL-10, IL-17 and transforming growth factor-β (TGF-β) levels, and the expression of forkhead box protein 3 (Foxp3) and retinoid-related orphan nuclear receptor γt (Rorγt) was measured. AIN rats developed severe albuminuria, hypoalbuminaemia, hyperlipidaemia and podocyte injury. Daily administration of MAT (100mg/kg or 200mg/kg) significantly prevented ADR-induced podocyte injury, decreased AIN symptoms and improved renal pathology manifestations. Of note, treatment with MAT (100mg/kg) plus prednisone (Pre, 5mg/kg) had equivalent efficacy to that of Pre alone (10mg/kg). Additional findings showed that ADR triggered a disordered cytokine network and abnormal expression of Foxp3 and Rorγt in rats, as reflected by increased levels of IL-6, IL-10, TGF-β, Rorγt and decreased levels of IL-10 and Foxp3. Interestingly, MAT weakened the disordered cytokine network and normalized the expression of Foxp3 and Rorγt. In addition, a significant negative correlation was observed between the values of Foxp3/Rorγt and renal pathology scores. Finally, MAT normalized regulatory T cells (Treg)/ T-helper17 cells (Th17) ratio in peripheral blood mononuclear cells of AIN rats. These data indicate MAT prevents AIN through the modification of disordered plasma lipids and recovery of renal function, and this bioactivity is at least partly attributed to the suppression of renal inflammation and the regulation of the Treg/Th17 imbalance.
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Pathophysiology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Hongzhou
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Lingfang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Jieqiu
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, the Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: wangdexuan2012@sina.com.
authors.forename: Dexuan
authors.initials: D
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002452:Cell Count; D004317:Doxorubicin / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000473:pathology; D011507:Proteinuria / Q000150:complications; D011807:Quinolizines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects*; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011807:Quinolizines; D004317:Doxorubicin; D000093842:Matrines
keywords: Adriamycin-induced nephropathy; Matrine; Proteinuria; Th17 cells; Treg cells; adriamycin (PubChem CID: 31703); matrine (PubChem CID: 91466); prednisone (PubChem CID: 5865)