Hyperproliferation and oxidative stress induced by hyperglycemia in mesangial cells plays crucial roles in the pathological process of diabetic nephropathy. Farrerol, isolated from rhododendron leaves, possesses broad anti-oxidative and anti-inflammatory properties towards several diseases, but its role in diabetic neuropathy remains unclear. The aim of this study was to evaluate the effects of farrerol in high glucose induced mesangial cell injury, and to explore underlying molecular mechanisms. Our results showed that high glucose in vitro conditions significantly stimulated cell proliferation, inflammatory cytokine secretion, extracellular matrix deposition, excessive oxidative stress, and NADPH oxidase activity in mesangial cells. Levels of NADPH oxidase 4 (Nox4) expression, ERK1/2 phosphorylation, and TGF-β1/Smad2 activation were significantly induced by high glucose conditions in mesangial cells. Inversely, farrerol treatments at 40, 60, and 80 μM concentrations, dose-dependently alleviated this molecular damage by high glucose in mesangial cells. We also found that restoration of Nox4 expression abolished the protective effects of farrerol on high glucose-induced proliferation and reactive oxygen species generation. Furthermore, pretreatment with the Nox4 inhibitor diphenyliodonium or the ERK1/2 pathway inhibitor PD98059, displayed similar ameliorated effects of farrerol on high glucose-induced mesangial cell damage. Taken together, these data suggest that farrerol displays protective effects on high glucose induced mesangial cell injury, partly through the Nox4-mediated ROS/ERK1/2 signaling pathway. These observations may provide novel insights into the application of farrerol as a diabetic neuropathy treatment.
Keywords: Diabetic neuropathy; Farrerol; High glucose; Mesangial cells; Nox4; ROS.
Copyright © 2019 Elsevier B.V. All rights reserved.