Aloperine attenuates high glucose-induced oxidative injury in Schwann cells via activation of NRF2/HO-1 pathway

Yiran Chen,Sijia Liu,Tieming Ma,Zhimin Wang,Lianqun Jia,Xiaoqing Zhang,Qingxuan He

doi:10.4314/tjpr.v19i6.4

Abstract

Purpose: To determine the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the action of aloperine on Schwann cell injury caused by high glucose (HG).Methods: Cell viability was determined using MTT assay while the release of lactate dehydrogenase (LDH) was determined by biochemical assay. Apoptosis was assessed using flow cytometry, while the levels of malondialdehyde (MDA) were determined by Annexin V-FIT staining. Glutathione Stransferase (GST), glutathione peroxidase (GPX), and reactive oxygen species (ROS) were determined using enzyme-linked immunosorbent assay.Results: Treatment with HG suppressed RSC96 cell viability and increased LDH release, while aloperine reversed these results (p < 0.05). Apoptosis of RSC96 cells was induced by HG stimulation, but was abolished by aloperine. The levels of ROS, MDA, and GST were enhanced in cells followingtreatment with HG, but was reversed by aloperine (p < 0.05). The decreased level of GPX caused by HG in RSC96 cells was elevated by aloperine. Moreover, aloperine upregulated NRF2 and HO-1 in RSC96 cells treated with HG (p < 0.05).Conclusion: Aloperine attenuates HG-induced oxidative injury in Schwann cells via activation of NRF2/HO-1 pathway, suggesting its potential as a potent drug for the management of diabetic peripheral neuropathy. Keywords: Aloperine, Schwann cells, High glucose, Oxidative stress, NRF2, HO-1

Highlights

Diabetic peripheral neuropathy (DPN) is considered a common complication of diabetes mellitus (DM, type 2), which is characterized by peripheral nerve dysfunction [1,2]
Schwann cells exert a vital role in peripheral nerves [4], which are sensitive to hyperglycemia, and the injury in Schwann cells induced by oxidative stress under long-term hyperglycemia contributes to DPN [5]
Some studies have suggested that the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway is involved in the modulation of oxidative responses [8,9,10]

Summary

Introduction

Diabetic peripheral neuropathy (DPN) is considered a common complication of diabetes mellitus (DM, type 2), which is characterized by peripheral nerve dysfunction [1,2]. In retinal pigment epithelial cells, salvianolic acid A can prevent oxidative stress through activation of the NRF2/HO-1 pathway [8]. This signaling pathway mediates the HG-induced Schwan cell injury [11], and participates in the regulatory process of Schwan cell injury induced by HG [11]. This signaling pathway is essential for alleviating oxidative injury in Schwann cells

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Conclusion