Notoginsenoside R1 alleviates high glucose-evoked damage in RSC96 cells through down-regulation of miR-503

摘要

Notoginsenoside R1 (NGR1) is a major bioactive ingredient of Radix notoginseng that has promise in treating several diabetes-related diseases, like diabetic nephropathy and diabetic cardiomyopathy. This work is designed to explore if NGR1 has potential in treating diabetic peripheral neuropathy (DPN). A cell model of DPN was made by stimulating RSC96 cells with high glucose. The effects of NGR1 preconditioning were examined by conducting CCK-8 assay, flow cytometry, ROS assay and Western blot. The downstream effector and signalling of NGR1 were then explored by qRT-PCR and Western blot. High glucose incubation led to cell viability loss, apoptosis facilitation, caspase-3 and PARP cleavage, and ROS generation of RSC96 cells. Meanwhile, expression of NGF and BDNF was declined by high glucose. Preconditioning NGR1 significantly protected RSC96 cells against high glucose-evoked damage. And NGR1 prevented high glucose-induced expression of miR-503. The beneficial functions of NGR1 towards high glucose-injured RSC96 cells were impeded by miR-503 overexpression. Further, NGR1 activated PI3K/AKT and β-catenin signalling through a miR-503-dependent way. This paper illustrated the neuroprotective and neurotrophic function of NGR1 in RSC96 cells. The beneficial function may due to its regulation on miR-503 expression and the downstream signalling such as PI3K/AKT and β-catenin.