Abstract
Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin’s effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT–PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin’s antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation.
Highlights
Diabetic neuropathy is a common microvascular complication of both type 1 and type 2 diabetes mellitus
This study examined the impact of high glucose on Schwann cells and whether loganin could protect against high-glucose-induced cell death
This study provides the first evidence that loganin treatment reduces the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes and subsequent pyroptosis by inhibiting reactive oxygen species (ROS) generation in high-glucose-treated RSC96 Schwann cells
Summary
Diabetic neuropathy is a common microvascular complication of both type 1 and type 2 diabetes mellitus. The global prevalence of diabetic peripheral neuropathy (DPN) is ~30% in type 2 diabetic patients and ~26% in type 1 diabetic patients with an overall incidence of ~29% [1,2]. It is generally agreed that hyperglycemia mainly contributes to the development of diabetic neuropathy or DPN. DPN caused neuroinflammation, peripheral nerve injury, reduced nerve conduction velocity and altered the nerve fiber Na+ , K+ -ATPase activity, which provokes reactive oxygen species (ROS) release [3]. DPN is the most frequently occurring complication in type 2 diabetes and often affects sensory and motor neurons of peripheral nerves causing pain and discomfort in lower extremities, risk of foot ulcerations and reduced quality of life [4,5].
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