Abstract
Hyperglycemia is a potent risk factor for the development and progression of diabetes-induced
nephropathy. Dendropanoxide (DPx) is a natural compound isolated from Dendropanax morbifera (Araliaceae) that exerts various biological effects. However, the role of DPx in
hyperglycemia-induced renal tubular cell injury remains unclear. The present study
explored the protective mechanism of DPx on high glucose (HG)-induced cytotoxicity
in kidney tubular epithelial NRK-52E cells. The cells were cultured with normal glucose
(5.6 mM), HG (30 mM), HG + metformin (10 µM), or HG + DPx (10 µM) for 48 h, and cell
cycle and apoptosis were analyzed. Malondialdehyde (MDA), advanced glycation end products
(AGEs), and reactive oxygen species (ROS) were measured. Protein-based nephrotoxicity
biomarkers were measured in both the culture media and cell lysates. MDA and AGEs
were significantly increased in NRK-52E cells cultured with HG, and these levels were
markedly reduced by pretreatment
with DPx or metformin. DPx significantly reduced the levels of kidney injury molecule-1
(KIM-1), pyruvate kinase M2 (PKM2), selenium-binding protein 1 (SBP1), or neutrophil
gelatinase-associated lipocalin (NGAL) in NRK-52E cells cultured under HG conditions.
Furthermore, treatment with DPx significantly increased antioxidant enzyme activity.
DPx protects against HG-induced renal tubular cell damage, which may be mediated by
its ability to inhibit oxidative stress through the protein kinase B/mammalian target
of the rapamycin (AKT/mTOR) signaling pathway. These findings suggest that DPx can
be used as a new drug for the treatment of high glucose-induced diabetic nephropathy.
Key words
Dendropanax morbifera (Araliaceae) - hyperglycemia - dendropanoxide - high glucose - advanced glycation
end-product - reactive oxygen species
