Osteomeles schwerinae extracts inhibits the binding to receptors of advanced glycation end products and TGF-β1 expression in mesangial cells under diabetic conditions

Abstract

Background: Osteomeles schwerinae C. K. Schneid. (Rosaceae, OSSC) is a medicinal plant traditionally used to treat various diseases in Asia. The chemical constituents of OSSC have an inhibitory effect on aldose reductase activity, which has been implicated in the pathogenesis of diabetic complications. However, the protective effects of the pharmacological activity and potential mechanisms in diabetic nephropathy are still not known.

Objective: In the present study, OSSC extracts and major compounds were examined for their effects on binding to the receptors of advanced glycation end products (RAGE) and on transforming growth factor-beta1 (TGF-β1) expression-related signal mechanisms in mouse glomerular mesangial cells (GMCs).

Materials and methods: A simple, rapid and efficient method was developed for the simultaneous determination of the marker compounds in the ethanol extract of the leaves and twigs of OSSC using HPLC-diode array detector (DAD). In this study, we determined the effects of OSSC extract and hyperoside on AGE and RAGE binding, and studied the mechanism of OSSC extract effects on AGE-bovine serum albumin (BSA)-treated GMCs. GMCs overexpressing human RAGE were cultured in AGE-BSA labeled with Alexa 488, and OSSC extract. AGE/RAGE binding were measured using fluorescence (excitation 485 nm/emission 528 nm). TGF-β1 protein expression levels were determined by western blot analyses.

Results: OSSC extracts of leaves and twigs inhibited on AGE/RAGE binding and TGF-β1 protein expression in a dose-dependent manner in GMCs. Furthermore, OSSC extracts reduced the effects on AGE-BSA-induced reactive oxidative species (ROS) formation and nuclear translocalization of transcription factor NF-κB. OSSC extracts inhibited phosphorylation of extracellular signal-regulated protein kinases1/2 (ERK1/2), p38 mitogen-activated protein kinases (p38MAPK), and IκB. Hyperoside also inhibited AGE/RAGE binding and ROS formation, and reduced TGF-β1 expression and IkB phosphorylation.

Conclusions: OSSC extracts and hyperoside may attenuate AGE/RAGE binding and expression of TGF-β1 by downregulating of pERK1/2, p38MAPK and IκB phosphorylations in GMCs under diabetic condition and retard the development of diabetic complications such as diabetic nephropathy.

Keywords: Advanced glycation end products; Diabetic nephropathy; Glomerular mesangial cell; Hyperoside; Osteomeles schwerinae; Transforming growth factor-beta1.