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.

中文翻译：

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Notoginsenoside R1 通过下调 miR-503 减轻 RSC96 细胞中高糖诱发的损伤。

三七皂甙 R1 (NGR1) 是三七的主要生物活性成分，有望治疗多种糖尿病相关疾病，如糖尿病肾病和糖尿病心肌病。这项工作旨在探索 NGR1 是否具有治疗糖尿病周围神经病变 (DPN) 的潜力。通过用高糖刺激RSC96细胞制作DPN细胞模型。通过进行CCK-8测定、流式细胞术、ROS测定和Western印迹检查NGR1预处理的效果。然后通过qRT-PCR和Western印迹探索NGR1的下游效应器和信号传导。高葡萄糖温育导致细胞活力丧失、细胞凋亡促进、caspase-3 和 PARP 裂解以及 RSC96 细胞的 ROS 生成。同时，高糖降低了NGF和BDNF的表达。预处理 NGR1 显着保护 RSC96 细胞免受高葡萄糖诱发的损伤。NGR1 阻止了高糖诱导的 miR-503 的表达。NGR1 对高葡萄糖损伤的 RSC96 细胞的有益功能受到 miR-503 过表达的阻碍。此外，NGR1 通过 miR-503 依赖的方式激活 PI3K/AKT 和 β-catenin 信号传导。本文阐述了 NGR1 在 RSC96 细胞中的神经保护和神经营养功能。有益功能可能是由于其对 miR-503 表达和下游信号传导（如 PI3K/AKT 和 β-连环蛋白）的调节。NGR1 通过 miR-503 依赖的方式激活 PI3K/AKT 和 β-catenin 信号传导。本文阐述了 NGR1 在 RSC96 细胞中的神经保护和神经营养功能。有益功能可能是由于其对 miR-503 表达和下游信号传导（如 PI3K/AKT 和 β-连环蛋白）的调节。NGR1 通过 miR-503 依赖的方式激活 PI3K/AKT 和 β-catenin 信号传导。本文阐述了 NGR1 在 RSC96 细胞中的神经保护和神经营养功能。有益功能可能是由于其对 miR-503 表达和下游信号传导（如 PI3K/AKT 和 β-连环蛋白）的调节。