Tangeretin inhibits high glucose-induced extracellular matrix accumulation in human glomerular mesangial cells

• Published in: Biomedicine & pharmacotherapy Vol. 102; pp. 1077 - 1083
• Main Authors: Chen, Fang, Ma, Yali, Sun, Zhiqiang, Zhu, Xiaoguang
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2018
• Subjects: Cell Cycle - drug effects; Cell Cycle - genetics; Cell Line; Cell Proliferation - drug effects; Collagen Type IV - metabolism; Diabetic nephropathy; Enzyme Activation - drug effects; Extracellular matrix (ECM); Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Fibronectins - metabolism; Flavones - pharmacology; Gene Expression Regulation - drug effects; Glucose - toxicity; Humans; Malondialdehyde - metabolism; MAP Kinase Signaling System - drug effects; Mesangial cells (MCs); Mesangial Cells - drug effects; Mesangial Cells - enzymology; Mesangial Cells - metabolism; Mesangial Cells - pathology; NADPH Oxidases - metabolism; Reactive Oxygen Species - metabolism; Superoxide Dismutase - metabolism; Tangeretin; Transforming Growth Factor beta1 - metabolism; Extracellular matrix (ECM); Diabetic nephropathy; Tangeretin; Mesangial cells (MCs)
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.03.169

[Display omitted] Tangeretin (5, 6, 7, 8, 4′-pentamethoxyflavone), a natural compound extracted from citrus plants, has been shown to possess a variety of pharmacological activities, including anti-oxidant, anti-tumor, cytostatic and anti-diabetic properties. However, the role of tangeretin in diabetic nephropathy (DN) has not yet been investigated. This study was undertaken to elucidate the effects of tangeretin on high glucose (HG)-induced oxidative stress and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) and explore the underlying mechanisms. Our results showed that tangeretin significantly inhibited HG-induced the proliferation of MCs. In addition, tangeretin dramatically reduced the levels of reactive oxygen species (ROS) and malondialdhyde (MDA), and induced SOD activity, as well as inhibited the expression of fibronectin (FN) and collagen IV in HG-stimulated MCs. Furthermore, tangeretin efficiently prevented the activation of ERK signaling pathway in HG-stimulated MCs. Taken together, these data indicated that tangeretin inhibits HG-induced cell proliferation, oxidative stress and ECM expression in glomerular MCs, at least in part, through the inactivation of ERK signaling pathway. Therefore, tangeretin may be a potential agent in the treatment of DN.