Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5829212 | European Journal of Pharmacology | 2012 | 9 Pages |
Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Hyperglycemia induces oxidative stress to generate reactive oxygen species in diabetic neurons resulting in neuronal damage and dysfunction. Apoptosis has been proposed as a possible mechanism for high glucose-induced neural dysfunction and neuronal cell injury. High glucose per se enhances lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression via activation of NADPH oxidase/reactive oxygen species pathway in endothelial cells. Selaginellin, a component extracted from Saussurea pulvinata (Hook. et Grev.) Maxim, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by high glucose. The differentiated PC12 cells were pretreated with various concentrations (10â7, 3Ã10â7 or 10â6Â M) of selaginellin for 1Â h and then co-treated with selaginellin and d-glucose (75Â mM) for 72Â h. Selaginellin was shown to protect differentiated PC12 cells against high glucose toxicity, as determined by characteristic morphological features, cell viability, and apoptosis as evaluated by Hoechst 33,258 staining assay, annexin V-propidium iodide double staining assay and caspase-3 activity. In addition, the increase in NADPH oxidase activity, mRNA expression of NADPH oxidase subunits (NOX-1 and NOX-2) and LOX-1, and reactive oxygen species production induced by high glucose were significantly inhibited by selaginellin or by anti-LOX-1 antibody. The present study demonstrated that inhibitory effect of selaginellin on high glucose-induced cell injury and apoptosis in differentiated PC12 cells is related to inhibition of LOX-1/NADPH oxidase-reactive oxygen species/caspase-3 signaling pathway.