Abstract
BackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.
Highlights
Many studies have reported that severe spinal cord injury (SCI) leads to neuronal death and axonal loss in the local microenvironment, eventually resulting in a devastating loss of function [1,2]
We observed that the survival rate of cerebellar granule neurons (CGNs) was increased in response to EGCG treatment in a dosedependent manner, with a peak level observed at a concentration of 50 μM (Figure 1a)
A similar pattern for protein kinase D1 (PKD1) phosphorylation levels was observed (Figure 1b). These results revealed that EGCG treatment at a concentration of 50 μM can increase the CGN cell survival rate with a maximum effect
Summary
Many studies have reported that severe spinal cord injury (SCI) leads to neuronal death and axonal loss in the local microenvironment, eventually resulting in a devastating loss of function [1,2]. (−)-Epigallocatechin-3-gallate (EGCG), the major catechin found in green tea (Camellia sinensis), has been extensively investigated as the predominant active polyphenol and a promising therapeutic agent for the treatment of chronic inflammation and oxidative damage-related diseases [5,6,7]. Several experimental studies have shown that EGCG can provide neuroprotection against brain injury, SCI, and sciatic nerve injury [11,12]. These benefits are mainly due to free radical scavenging or the antioxidant and anti-apoptotic properties of EGCG [13,14].
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