title: KS370G, a caffeamide derivative, attenuates unilateral ureteral obstruction-induced renal fibrosis by the reduction of inflammation and oxidative stress in mice.
abstract: Unilateral ureteral obstruction (UUO) is an established animal model used to study renal nephropathy. Caffeic acid phenethyl ester, a natural phenolic compound, possesses antifibrotic, anti-inflammation and anti-oxidative stress effects; however, rapid decomposition by esterases substantially decreases its bioavailability. The goal of this study was to investigate the beneficial effects of KS370G, a synthetic caffeamide derivative, on UUO-induced renal injury. Following the UUO, KS370G (10mg/kg) was administered by oral gavage once a day. Renal injury was analyzed at 14 days post-operation. Our results show that KS370G significantly attenuated collagen deposition in the obstructed kidney and inhibited UUO-induced renal fibrosis markers expression, including fibronectin, type I collagen, vimentin, and α-smooth muscle actin (α-SMA). KS370G significantly lowered the expression of renal inflammatory chemokines/adhesion molecules and monocyte cells marker (MCP-1, VCAM-1, ICAM-1 and CD11b). KS370G also reduced renal malondialdehyde levels and reversed the expression of renal antioxidant enzymes (SOD and catalase) after UUO. Furthermore, KS370G significantly inhibited UUO-induced elevated plasma AngII and TGF-β1 levels, TGF-β1 protein expression and Smad3 phosphorylation. These findings demonstrate that KS370G reduces renal obstructive nephropathy by possibly inhibiting AngII, TGF-β and Smad3 signaling pathways.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Sung-Ting
authors.initials: ST
authors.lastname: Chuang
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan; Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan. Electronic address: mingja@ntu.edu.tw.
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D002109:Caffeic Acids; D015815:Cell Adhesion Molecules; D018925:Chemokines; D024042:Collagen Type I; D005353:Fibronectins; C554967:KS370G; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Caffeamide; Obstructive nephropathy; Renal fibrosis; Unilateral ureteral obstruction