Thymoquinone Alleviates the Experimental Diabetic Peripheral Neuropathy by Modulation of Inflammation.

Biqin Chen,Yiye Shao,Yinghui Chen,Qiong Luo,Long Chen,Bing Li,Xiaohong Shi

doi:10.1038/srep31656

Abstract

Thymoquinone has been reported to exhibit antioxidant and anti-inflammatory effects. Inflammation plays an important role in pathogenesis of diabetic peripheral neuropathy. This study investigated the effects of TQ on proliferation and apoptosis of Schwann cells exposed to high glucose conditions and electrophysiological and morphological changes of the sciatic nerve in a DPN rat model as well as relevant inflammatory mechanism. Cell proliferation and apoptosis of Schwann cells were measured using the Cell Counting Kit-8 and flow cytometry. DPN model was established in streptozotocin-induced diabetic rats. Nerve conduction velocity was measured before and after treatment. Morphologic changes were observed by H&E staining and transmission electron microscopy. COX-2, IL-1β, IL-6, and Caspase-3 expression was investigated by western blotting and Bio-Plex ProTM Assays. Finally, TQ alleviated the inhibition of Schwann cell proliferation and protected against Schwann cell apoptosis. It improved nerve conduction velocity, and alleviated the DPN-induced morphological changes and demyelination of the sciatic nerve. COX-2, IL-1β, IL-6 and Caspase-3 expression in sciatic nerve or isolated cultured Schwann cells, were also decreased by TQ. These results indicate TQ has a protective effect on peripheral nerves in a DPN rat model. The mechanism may be mediated partly by the modulation of the inflammatory reaction.

Highlights

Thymoquinone (TQ) is a bioactive monomer derived from black seed (Nigella sativa) oil
TQ alleviated the inhibition of Schwann cell proliferation following exposure to a high of concentration glucose
To verify whether TQ could inhibit the inflammatory reactions induced by high a concentration of glucose and LPS, we examined the levels of COX-2, which plays an important role in inflammatory response in Schwann cells treated with 100 mM glucose and 1 μg/mL LPS

Summary

Introduction

Thymoquinone (TQ) is a bioactive monomer derived from black seed (Nigella sativa) oil. M had proved that thymoquinone had beneficial effects on histopathological changes of sciatic nerves in STZ-induced diabetic peripheral neuropathy rats by regulating oxidative stress[19]. It is not clear whether inflammatory response was involved in this process, after all, thymoquinone has a strong anti-inflammatory effect while inflammatory reaction participates in the pathogenesis of DPN. We report that TQ protects against glucose-induced apoptosis of Schwann cells and inhibition of Schwann cell proliferation in cultured cells It improves nerve conduction velocity, and alleviates pathological morphology changes and sciatic nerve demyelination in DPN rats. Differential expression of COX-2, IL-1β, IL-6, and Caspase-3 between TQ-treated and untreated rats suggests that these effects may be mediated by the inflammatory response

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Results

Conclusion