TY  - EJOU
AU  - Ma, Guoxu 
AU  - Huang, Yonglu 
AU  - Gong, Fan 
AU  - Wu, Jianke 
AU  - Ding, Yi 
AU  - Zhang, Ziyang 
AU  - Li, Xiaoliang 
AU  - Gao, Jian 
AU  - Dang, Tingting 
AU  - Zhang, Bowen 

TI  - Lycium Barbarum Polysaccharides Upregulate Trx2 in Schwann Cells through ESR1 to Repair Sciatic Nerve Injury in Rats
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <b>Objectives:</b> Sciatic nerve injury (SNI) impairs quality of life, and <i>Lycium barbarum polysaccharides</i> (LBP) may exert therapeutic effects via regulating Schwann cell (SC) mitochondrial stability, though the mechanism remains unclear. The study aimed to elucidate the therapeutic mechanisms of LBP in mitigating sciatic nerve injury by protecting Schwann cells via the estrogen receptor 1 (ESR1)/thioredoxin 2 (Trx2) pathway. <b>Methods:</b> An <i>in vitro</i> SNI model was established by inducing RSC96 cells with H<sub>2</sub>O<sub>2</sub>. Cell counting kit-8 (CCK8) assay, enzyme-linked immunosorbent assay (ELISA), Western blot, reactive oxygen species (ROS) and adenosine triphosphate (ATP) quantification, and mitochondrial membrane potential (MMP) detection were used to evaluate cellular functions and molecular changes. Network pharmacology and molecular docking were employed to predict potential targets of LBP. Chromatin immunoprecipitation (ChIP) assays verified the interaction between ESR1 and Trx2, and ESR1 was knocked down in SCs to confirm the regulatory pathway. Additionally, <i>in vivo</i> validation was performed using a rat SNI model. <b>Results:</b> LBP intervention significantly reduced H<sub>2</sub>O<sub>2</sub>-induced mitochondrial dysfunction, inflammation, and oxidative stress in RSC96 cells (<i>p</i> &lt; 0.05). It also regulated the expression of apoptosis-related proteins, Trx2, and mitochondrial apoptosis-inducing factor (AIF; <i>p</i> &lt; 0.001). Network pharmacology and molecular docking identified ESR1 as a key target of LBP, and ChIP assays confirmed that ESR1 promoted Trx2 transcription. Moreover, LBP enhanced SC proliferation (OD<sub>450</sub> at day 5 = 1.25-fold; colony formation = 1.85-fold), increased MMP and ATP levels (MMP = 2.25-fold; ATP = 1.75-fold), inhibited inflammation, and reduced apoptosis (<i>p</i> &lt; 0.001), while ESR1 knockdown abrogated these effects (<i>p</i> &lt; 0.05). In rat SNI models, LBP effectively alleviated nerve injury (<i>p</i> &lt; 0.001). <b>Conclusion:</b> LBP may modulate Trx2 via ESR1 for the purpose of restoring the dysfunction of SCs induced by H<sub>2</sub>O<sub>2</sub>. This potentially offers a new strategy for the therapy of SNI.
KW  - <i>Lycium barbarum</i> polysaccharide (LBP); sciatic nerve injury (SNI); Schwann cells (SCs); estrogen receptor 1 (ESR1); thioredoxin 2 (Trx2); mitochondrial membrane potential (MMP)

DO  - 10.32604/biocell.2026.078402