Diosgenin Glucoside Protects against Spinal Cord Injury by Regulating Autophagy and Alleviating Apoptosis.

Xian-Bing Chen,Kui Zhang,Zong-Hai Chen,Zi-Li Wang,Fang-Yu Zhao,Xiao-Li Qin,Qing-Yu Yang,Xian-E Tang,Jun-Long Du,Fei-Jun Huang

doi:10.3390/ijms19082274

Abstract

Spinal cord injury (SCI) is a severe traumatic lesion of central nervous system (CNS) with only a limited number of restorative therapeutic options. Diosgenin glucoside (DG), a major bioactive ingredient of Trillium tschonoskii Max., possesses neuroprotective effects through its antioxidant and anti-apoptotic functions. In this study, we investigated the therapeutic benefit and underlying mechanisms of DG treatment in SCI. We found that in Sprague-Dawley rats with traumatic SCI, the expressions of autophagy marker Light Chain 3 (LC3) and Beclin1 were decreased with concomitant accumulation of autophagy substrate protein p62 and ubiquitinated proteins, indicating an impaired autophagic activity. DG treatment, however, significantly attenuated p62 expression and upregulated the Rheb/mTOR signaling pathway (evidenced as Ras homolog enriched in brain) due to the downregulation of miR-155-3p. We also observed significantly less tissue injury and edema in the DG-treated group, leading to appreciable functional recovery compared to that of the control group. Overall, the observed neuroprotection afforded by DG treatment warrants further investigation on its therapeutic potential in SCI.

Highlights

Spinal cord injury (SCI) remains a rare disease in comparison to traumatic brain injury, concussion, or stroke in the younger population, but it can cause permanent disability or loss of movement and sensation
MiR-155 can bind to the 3 -untranslated region (UTR) of the target genes such as Ras homolog enriched in brain (Rheb) and serine/threonine kinase p70S6 kinase (p70S6K), thereby negatively regulating autophagy in the body
We aimed to evaluate the effect of Diosgenin glucoside (DG) on post-injury recovery of motor function and neuronal apoptosis in rats with experimental SCI, and we determine whether autophagy induced by miR-155-3p/Rheb/mTOR signal pathway is involved in the protection of SCI and in the repair of damaged neurons

Summary

Introduction

Spinal cord injury (SCI) remains a rare disease in comparison to traumatic brain injury, concussion, or stroke in the younger population, but it can cause permanent disability or loss of movement and sensation. The pathological and repairing mechanisms of SCI mainly focuses on the prevention and reversible regulation of secondary injury of spinal cord, which will provide reliable clinical treatment strategies for the recovery and regeneration of neurons after SCI. Endogenous non-coding microRNAs (miR) have been found to have the function to regulate autophagy through modulating autophagy-related proteins. During SCI progression, many microRNAs have been differentially expressed to execute the important regulatory functions for injury repairing [13,14]. It is the focus of current biological research to clarify the regulatory mechanisms of microRNAs involved in the repairing of SCI. With the exploration of the correlation between microRNAs the and spinal cord, and corresponding regulatory mechanisms of microRNAs, microRNAs have a high potential as targets or drug mimics of SCI therapy, which will provide novel therapeutic strategies for SCI

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