LAUSR

BACKGROUND Diabetic foot is a severe complication of diabetes mellitus, mainly caused by diabetic peripheral neuropathy. The objective of this study was to investigate the function of emodin (a neuroprotective agent reported previously) in diabetic peripheral neuropathy. METHODS A neuron-like cell line PC-12 was subjected with high level glucose, before which emodin was applied to treat cells. The expression of miR-9 in cell was overexpressed or suppressed by miRNA transfection. Thereafter, cell viability, apoptosis and autophagy were assessed, respectively. RESULTS High glucose exhibited cytotoxicity in PC-12 cells. Emodin protected PC-12 cells against high glucose-induced apoptosis and viability impairment. These observations were coupled with the down-regulations of p21, p16, Bax, cleaved caspase-3 and -9, and the up-regulations of CyclinD1 and Bcl-2. Additionally, high glucose-induced autophagy was alleviated by emodin, as Beclin-1 was down-regulated, p62 was up-regulated, and the conversion of LC3-I to LC3-II was decreased. miR-9 was highly expressed in response to emodin treatment. More interestingly, the protective actions of emodin on high glucose-induced injury were reversed by miR-9 suppression. Also, the activation of PI3K/AKT signaling and deactivation of NF-κB signaling induced by emodin were recovered by miR-9 suppression. CONCLUSION Emodin protected PC-12 cells against high glucose-induced apoptosis and autophagy. The neuroprotective activities might be realized by up-regulation of miR-9, and modulation of PI3K/AKT and NF-κB signaling pathways.